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Neuroscience

Neuroscience Breakthrough Unveils How We Learn and Remember – SciTechDaily

New findings in memory research reveal the role of dendritic translation in learning, identifying thousands of micropeptides and key regulatory proteins, offering insights into intellectual disabilities and broader neurological functions. Credit: SciTechDaily.com

Activity taking place within the dendrites that branch off of neuron cell bodies is key to memory formation.

Less than twenty minutes after finishing this article, your brain will begin to store the information that youve just read in a coordinated burst of neuronal activity. Underpinning this process is a phenomenon known as dendritic translation, which involves an uptick in localized protein production within dendrites, the spiny branches that project off the neuron cell body and receive signals from other neurons at synapses. Its a process key to memoryand its dysfunction is linked to intellectual disorders.

That makes the inner workings of dendritic translation a holy grail for understanding memory formation, says Rockefellers Robert B. Darnell, whose team just published a study in Nature Neuroscience describing a new platform capable of identifying the specific regulatory mechanisms that drive dendritic translation. The team leveraged a method, dubbed TurboID, to discover an entire suite of previously unknown factors in memory formation, revealing now mechanisms that underlie how protein synthesis in dendrites contributes to learning and memory. The findings may also have implications for intellectual disabilities, such as Fragile X syndrome.

Technological limitations have long prevented a comprehensive inventory of the activity at the synapse involved in memory formation, says lead author Ezgi Hacisuleyman, who conducted the research as a postdoctoral researcher in Darnells laboratory. She is now an assistant professor at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology. Our new techniques can accomplish this with extremely high resolution to look at neurons in vitro that are closely mimicking what we see in the brain.

Hacisuleymans work defines a whole new biochemical pathway which fits with, complements, and vastly expands what we already knew about memory and learning, adds Darnell, the Robert and Harriet Heilbrunn professor.

Memory formation centers around the hippocampus, a brain region so central to learning that, when surgeons removed it from people with epilepsy in the 1940s, the patients remembered their childhoods but lost the ability to form new memories. It has since become clear that memories form, in part, because of new protein synthesis made locally in the dendrites of the hippocampus.

Darnell, a physician-scientist, observed the importance of dendritic translation firsthand while working with patients whose immune systems had attacked the hippocampus. I would talk to a patient for 30 minutes, leave the room, walk back in, and it was like they had never seen me before, he says. Thats when I began focusing on why neurons of the hippocampus have their own system for regulating RNA metabolisma system that no other cell in the body uses.

That system, it turns out, lies at the heart of how our brains form memories and learn new information, and became a focus for the Darnell lab, culminating in his teams 2003 development of CLIP, a method that allowed researchers to study the proteins that bind and influence RNA. But limitations remained. Many details about how neurons respond to stimuli at the dendrites were still missing, Hacisuleyman says. We needed that information, because that plays a role in determining how neurons functionand where things often go awry in neurologic disease.

To get a better idea of the role that changes in dendrites play in learning, Hacisuleyman extended the TurboID platform to works in concert with RNA-sequencing, CLIP, translation and protein analysis. The platform allowed the team to track activity in dendrites before, during, and several minutes after the neuron activates, capturing the moments critical to protein synthesis in the cell and, more importantly, the stage considered key to memory formation.

An analysis of these crucial moments revealed a microscopic upheaval in the dendrite. Upon activation, local ribosomes jump onto mRNAs, an action that has all the biochemical hallmarks of memory formation, and which models predicted will cause the dendrite to produce not only new proteins, but 1,000 small proteins known as micropeptides, with as-yet unknown function. The team also identified an RNA-binding protein that helps seal the connection between these ribosomes and mRNA, and demonstrated that if that protein is disabled, the proposed micropeptides and their associated downstream proteins will not form.

We never knew these micropeptides might even exist, Darnell says. It opens a new field of study, where we can ask what these peptides might be doing and how they could play into memory formation. Its such a vast discovery that there are dozens if not hundreds of avenues in which to pursue this.

Among the many observations that researchers will unpack in future studies, one stood out: the team noted that a certain protein stood out for its prolific binding of mRNA in the dendrite. The protein, called FMRP, is key to brain development and function, and genetic mutations that adversely impact FMRP contribute to Fragile X syndrome, one of the most common genetic causes of intellectual disability. Our findings fit nicely with the molecular biology of FMRP, and also open the door to future insights into what is going wrong in Fragile X, Darnell says.

Beyond the papers immediate findings, dendritic-TurboID could also allow researchers to examine RNA regulation and protein synthesis in other brain regions and apply the findings to different diseases. We can now begin to look at many other sites with a fine-toothed comb, Hacisuleyman says.

When you develop a new technique as Hacisuleyman did, you enter a room that nobody has ever been in before, Darnell adds. The light turns on, and the findings just take your breath away.

Reference: Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding by Ezgi Hacisuleyman, Caryn R. Hale, Natalie Noble, Ji-dung Luo, John J. Fak, Misa Saito, Jin Chen, Jonathan S. Weissman and Robert B. Darnell, 8 April 2024, Nature Neuroscience. DOI: 10.1038/s41593-024-01615-5

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Neuroscience Breakthrough Unveils How We Learn and Remember - SciTechDaily

Neuroscience

Pregnancy’s Toll: Accelerated Aging in Young Mothers – Neuroscience News

Summary: Pregnancy may accelerate biological aging in women. Utilizing advanced epigenetic clocks to measure DNA methylation, researchers compared the biological age of women with varying numbers of pregnancies against those who had never been pregnant, revealing that increased pregnancies correlate with signs of accelerated aging.

This effect was not observed in men, suggesting a unique biological cost associated with pregnancy and possibly breastfeeding. The findings, which highlight a significant gap in our understanding of the reproductive costs on womens health, point to the urgent need for supportive measures for young mothers, especially in contexts of limited resources.

Key Facts:

Source: Columbia University

Pregnancy may carry a cost, reports a new study from the Columbia University Mailman School of Public Health.

The research, carried out among 1735 young people in the Philippines, shows that women who reported having been pregnant looked biologically older than women who had never been pregnant, and women who had been pregnant more often looked biologically older than those who reported fewer pregnancies.

Notably, the number of pregnancies fathered was not associated with biological aging among same-aged cohort men, which implies that it is something about pregnancy or breastfeeding specifically that accelerates biological aging.

The findings are published inThe Proceedings of National Academy of Sciences.

This study builds on epidemiological findings that high fertility can have negative side effects on womens health and longevity. What was unknown, however, was whether the costs of reproduction were present earlier in life, before disease and age-related decline start to become apparent.

Until now, one of the challenges has been quantifying biological aging among the young. This challenge was overcome by using a collection of new tools that use DNA methylation (DNAm) to study different facets of cellular aging, health, and mortality risk. These tools, called epigenetic clocks allow researchers to study aging earlier in life, filling a key gap in the study of biological aging.

Epigenetic clocks have revolutionized how we study biological aging across the lifecourse and open up new opportunities to study how and when long-term health costs of reproduction and other life events take hold, said Calen Ryan PhD, lead author of the study and associate research scientist in the Columbia Aging Center.

Our findings suggest that pregnancy speeds up biological aging, and that these effects are apparent in young, high-fertility women, said Ryan.

Our results are also the first to follow the same women through time, linking changes in each womans pregnancy number to changes in her biological age.

The relationship between pregnancy history and biological age persisted even after taking into account various other factors tied to biological aging, such as socioeconomic status, smoking, and genetic variation, but were not present among men from the same sample.

This finding, noted Ryan, points to some aspect of bearing children rather than sociocultural factors associated with early fertility or sexual activity as a driver of biological aging.

Despite the striking nature of the findings, Ryan encourages readers to remember the context: Many of the reported pregnancies in our baseline measure occurred during late adolescence, when women are still growing.

We expect this kind of pregnancy to be particularly challenging for a growing mother, especially if her access to healthcare, resources, or other forms of support is limited.

Ryan also acknowledged that there is more work to do, We still have a lot to learn about the role of pregnancy and other aspects of reproduction in the aging process. We also do not know the extent to which accelerated epigenetic aging in these particular individuals will manifest as poor health or mortality decades later in life.

Ryan said that our current understanding of epigenetic clocks and how they predict health and mortality comes largely from North America and Europe, but that the aging process can take slightly different forms in the Philippines and other places around the world.

Ultimately I think our findings highlight the potential long-term impacts of pregnancy on womens health, and the importance of taking care of new parents, especially young mothers.

Co-authors are Christopher Kuzawa, Northwestern University, Nanette R. Lee and Delia B. Carba,USC-Office of Population Studies Foundation; Julie L. MacIsaac, David S. Lin, and Parmida Atashzay, University of British Columbia; Daniel BelskyColumbia Public Health and Columbia Aging Center; Michael S. Kobor, University of British Columbia, Canadian Institute for Advanced Research, Centre for Molecular Medicine and Therapeutics.

Funding: The study was supported by the National Institutes of Health R01AG061006; National Science Foundation BCS 1751912; University of British Columbia UBC 60055724

Author: Stephanie Berger Source: Columbia University Contact: Stephanie Berger Columbia University Image: The image is credited to Neuroscience News

Original Research: The findings will appear in PNAS

Continued here:
Pregnancy's Toll: Accelerated Aging in Young Mothers - Neuroscience News

Neuroscience

Learning and Memory Formation’s Molecular Basis – Neuroscience News

Summary: Researchers developed a new platform to explore dendritic translations role in memory formation and its implications for intellectual disorders. By employing a novel method named TurboID, researchers uncovered a suite of previously unknown factors involved in memory-related protein synthesis within dendrites, shedding light on the molecular mechanisms that could underlie conditions like Fragile X syndrome.

This study marks a significant advance in understanding how protein synthesis in dendrites contributes to learning and memory, potentially opening new pathways for treating neurodevelopmental disorders. The teams findings suggest that the localized production of proteins, including newly discovered micropeptides, within dendrites is crucial for memory formation, with implications for diseases characterized by memory impairment.

Key Facts:

Source: Rockefeller University

Less than twenty minutes after finishing this article, your brain will begin to store the information that youve just read in a coordinated burst of neuronal activity.

Underpinning this process is a phenomenon known as dendritic translation, which involves an uptick in localized protein production within dendrites, the spiny branches that project off the neuron cell body and receive signals from other neurons at synapses. Its a process key to memoryand its dysfunction is linked to intellectual disorders.

That makes the inner workings of dendritic translation a holy grail for understanding memory formation, says RockefellersRobert B. Darnell, whose team just publisheda study inNature Neurosciencedescribing a new platform capable of identifying the specific regulatory mechanisms that drive dendritic translation.

The team leveraged a method, dubbed TurboID, to discover an entire suite of previously unknown factors in memory formation, revealing now mechanisms that underlie how protein synthesis in dendrites contributes to learning and memory.

The findings may also have implications for intellectual disabilities, such as Fragile X syndrome.

Technological limitations have long prevented a comprehensive inventory of the activity at the synapse involved in memory formation, says lead author Ezgi Hacisuleyman, who conducted the research as a postdoctoral researcher in Darnells laboratory. She is now an assistant professor at The UF Scripps Institute.

Our new techniques can accomplish this with extremely high resolution to look at neurons in vitro that are closely mimicking what we see in the brain.

Hacisuleymans work defines a whole new biochemical pathway which fits with, complements, and vastly expands what we already knew about memory and learning, adds Darnell, the Robert and Harriet Heilbrunn professor.

A unique way to metabolize RNA

Memory formation centers around the hippocampus, a brain region so central to learning that, when surgeons removed it from people with epilepsy in the 1940s, the patients remembered their childhoods but lost the ability to form new memories.

It has since become clear that memories form, in part, because of new protein synthesis made locally in the dendrites of the hippocampus.

Darnell, a physician-scientist, observed the importance of dendritic translation firsthand while working with patients whose immune systems had attacked the hippocampus.

I would talk to a patient for 30 minutes, leave the room, walk back in, and it was like they had never seen me before, he says.

Thats when I began focusing on why neurons of the hippocampus have their own system for regulating RNA metabolisma system that no other cell in the body uses.

That system, it turns out, lies at the heart of how our brains form memories and learn new information, and became a focus for the Darnell lab, culminating in his teams 2003 development of CLIP, a method that allowed researchers to study the proteins that bind and influence RNA. But limitations remained.

Many details about how neurons respond to stimuli at the dendrites were still missing, Hacisuleyman says.

We needed that information, because that plays a role in determining how neurons functionand where things often go awry in neurologic disease.

1,000 micropeptides

To get a better idea of the role that changes in dendrites play in learning, Hacisuleyman extended the TurboID platform to works in concert with RNA-sequencing, CLIP, translation and protein analysis.

The platform allowed the team to track activity in dendrites before, during, and several minutes after the neuron activates, capturing the moments critical to protein synthesis in the cell and, more importantly, the stage considered key to memory formation.

An analysis of these crucial moments revealed a microscopic upheaval in the dendrite. Upon activation, local ribosomes jump onto mRNAs, an action that has all the biochemical hallmarks of memory formation, and which models predicted will cause the dendrite to produce not only new proteins, but 1,000 small proteins known as micropeptides, with as-yet unknown function.

The team also identified an RNA-binding protein that helps seal the connection between these ribosomes and mRNA, and demonstrated that if that protein is disabled, the proposed micropeptides will not form.

We never knew these micropeptides might even exist, Darnell says.

It opens a new field of study, where we can ask what these peptides might be doing and how they could play into memory formation. Its such a vast discovery that there are dozens if not hundreds of avenues in which to pursue this.

Among the many observations that researchers will unpack in future studies, one stood out: the team noted that a certain protein stood out for its prolific binding of mRNA in the dendrite.

The protein, called FMRP, is key to brain development and function, and genetic mutations that adversely impact FMRP contribute to Fragile X syndrome, one of the most common genetic causes of intellectual disability.

Our findings fit nicely with the molecular biology of FMRP, and also open the door to future insights into what is going wrong in Fragile X, Darnell says.

Beyond the papers immediate findings, dendritic-TurboID could also allow researchers to examine protein synthesis in other brain regions and apply the findings to different diseases.

We can now begin to look at many other sites with a fine-toothed comb, Hacisuleyman says.

When you develop a new technique as Hacisuleyman did, you enter a room that nobody has ever been in before, Darnell adds. The light turns on, and the findings just take your breath away.

Author: Katherine Fenz Source: Rockefeller University Contact: Katherine Fenz Rockefeller University Image: The image is credited to Neuroscience News

Original Research: Open access. Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding by Robert B. Darnell et al. Nature Neuroscience

Abstract

Neuronal activity rapidly reprograms dendritic translation via eIF4G2:uORF binding

Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear.

In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry.

Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated.

For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism.

This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control.

These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.

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Learning and Memory Formation's Molecular Basis - Neuroscience News

Neuroscience

Acetaminophen in Pregnancy Not Linked to Autism, ADHD Risk – Neuroscience News

Summary: A comprehensive study involving over 2.4 million Swedish children has debunked the notion that acetaminophen use during pregnancy increases the risk of autism, ADHD, and intellectual disability in offspring. The research employed a novel sibling comparison method to eliminate confounding familial and environmental factors, revealing no increased risk of neurodevelopmental disorders among siblings exposed to acetaminophen prenatally versus those who were not.

This finding challenges previous reports linking acetaminophen with such risks and offers reassurance to expectant parents regarding the safety of this common pain reliever during pregnancy.

Key Facts:

Source: Drexel University

In the largest study to date on the subject, researchers found no evidence to support a causal link between acetaminophen use during pregnancy and increased risk of autism, ADHD and intellectual disability in children.

The findings, using data from a nationwide cohort of over 2.4 million children born in Sweden, including siblings not exposed to the drug before birth, were published today in the Journal of theAmerican Medical Association(JAMA) from researchers atDrexels Dornsife School of Public HealthandKarolinska Institutetof Sweden.

Advertised as a pain reliever and fever reducer, the generic drug acetaminophen is the active ingredient in Tylenol and is an ingredient in versions of other drugs, such as Theraflu, Excedrin, and Mucinex, among others.

Following each child up to 26 years after birth, the team found a small increased risk of autism, ADHD and intellectual disability in the overall population as seen in similar previous studies that reported such a link.

However, the authors found no increased risk of any of the conditions when comparing full siblings when one sibling was exposed to acetaminophen while in the uterus before birth and the other sibling was not.

Because siblings share a substantial portion of their genetic background, as well as similar exposure to many of the same environmental factors during development, comparing siblings helps to control for these shared factors that are otherwise hard to measure in epidemiological studies, the authors noted.

Users of acetaminophen differ from non-users in a number of ways and standard statistical analyses without a sibling control cant control for all of the differences, said co-senior authorBrian Lee, PhD, an associate professor in DrexelsDornsife School of Public Health, fellow at theA.J. Drexel Autism Institute, and research affiliate at the Karolinska Institutet.

Sibling comparisons allow us to control for familial characteristics that might explain an apparent relationship between acetaminophen use during pregnancy and risk of neurodevelopmental conditions.

Using data from Swedens national health and prescription drug registers, the researchers gathered data on medication use throughout pregnancy for births from 1995 to 2019.

Only about 7.5% of the study sample 185,909 children were exposed to acetaminophen during pregnancy. In previous studies, acetaminophen use during pregnancy varied greatly depending on the study setting; astudyin Denmark reported 6.2% use while onestudyin the U.S. reported 10-fold higher use.

Previous studies suggested that many pregnant people, who may benefit from acetaminophen, do not take it for fear of side effects, such as a2019 studythat surveyed 850 pregnant Swedish persons, in which more than 60% considered medication use during early pregnancy to be probably harmful or harmful.

This studys findings may be welcome news for birthing people who use acetaminophen as a pain or fever management option, since there are few safe alternatives for relief available, said co-senior authorRenee M. Gardner, PhD, of Swedens Karolinska Institutet.

We hope that our results provide reassurance to expectant parents when faced with the sometimes fraught decision of whether to take these medications during pregnancy when suffering from pain or fever.

The authors say all patients should follow the guidance from their physician on whether acetaminophen is safe for them and their future children.

The study authors said that the statistically increased risk of neurodevelopmental disorders in children exposed to acetaminophen in the womb is likely due to other factors.

Our study and others suggest there are many different health and familial factors that are associated with both acetaminophen use and neurodevelopmental disorders, said Lee. Genetics likely play a role, but future work to elucidate this mechanism is crucial.

In 2015, theU.S. Food and Drug Administrationsaid that studies on over-the-counter pain medicines are too limited to make any recommendations, but noted that severe and persistent pain that is not effectively treated during pregnancy can result in depression, anxiety, and high blood pressure in the mother.

A 2021consensus statement inNature Reviews Endocrinologyby an international group of scientists and clinicians recommended that pregnant individuals minimize exposure (to acetaminophen) by using the lowest effective dose for the shortest possible time due to research suggesting that prenatal exposure to the drug could increase the risk of neurodevelopmental and other disorders.

Although the Drexel and Karolinskastudy used data on prescribed acetaminophen and reports from pregnant people to their midwives during prenatal care and may not capture all over-the-counter use in all patients, the findings represent data from a large representative sample and controls for many other factors that may be linked to neurodevelopmental disorders.

Funding: The study was supported by National Institutes of Healths National Institute of Neurological Disorders and Stroke 1R01NS107607. Beyond funding, NIH had no role in carrying out the study or interpretation of its findings. Lee has received consulting fees for literature reviews for law firms, but has provided no expert litigation, and no external parties had any role in the study.

Other than Gardner and Lee, other authors on the paper include shared lead authors Viktor H. Ahlqvist, PhD, and Hugo Sjqvist, Christina Dalman, MD, PhD, Hkan Karlsson, PhD, Olof Stephansson, MD, PhD, Stefan Johansson, MD, PhD, and Cecilia Magnusson, MD, PhD, all who hold academic appointments at the Karolinska Institutet.

Author: Greg Richter Source: Drexel University Contact: Greg Richter Drexel University Image: The image is credited to Neuroscience News

Original Research: The findings will appear in JAMA

Continued here:
Acetaminophen in Pregnancy Not Linked to Autism, ADHD Risk - Neuroscience News

Neuroscience

Childhood Loneliness Linked to Later Psychosis – Neuroscience News

Summary: Childhood loneliness significantly increases the likelihood of experiencing a psychotic episode later in life, particularly in women. Through an observational case-control study involving 285 first-episode psychosis patients and 261 controls, the research distinguished the effects of subjective loneliness from objective social isolation.

Key findings demonstrate that loneliness before age 12 doubles the risk of psychosis, with a notably stronger correlation in women. These insights emphasize the importance of early interventions targeting social connectedness to mitigate the risk of developing psychotic disorders.

Key Facts:

Source: European Psychiatric Association

A new study suggests that children who felt lonely for more than 6 months before the age of 12 are more likely to experience an episode of psychosis than children who did not, with women more affected than men.

Psychosis refers to a collection of symptoms that affect a persons mind, where there has been some loss of contact with reality.During an episode of psychosis, a person may have difficulty recognising what is real and what is not.

Symptoms of psychosis include hallucinations, delusions and confused thoughts.In some instances, psychosis may be a symptom of other mental health conditions, such as schizophrenia, bipolar disorder, or severe depression.

Symptoms of schizophrenia are often categorised as positive (any change in behaviour or thoughts, such as hallucinations or delusions), negative (where people appear to withdraw from the world around them).

Loneliness is defined as the subjective feeling of distress associated with a lack of meaningful relationships, regardless of the amount of social contact, whereas social isolation is defined as the objective lack of social contact or support.

In an observational, case-control study, researchers assessed loneliness in children with the question Have you ever felt lonely for more than 6 months before the age of 12 and differentiated this from social isolation by using the peer relationships item from the Premorbid Adjustment Scale.

The study sample comprised 285 patients who had experienced their first episode of psychosis and 261 controls.

Key findings from the study include:

Dr Covadonga Daz-Caneja of the Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Maran, Madrid, Spain, saidThere is increasing evidence of the negative health and social consequences of loneliness in adults, but much less is known about the long-term effects of loneliness in young people.

Despite their preliminary nature, our results suggest that childhood loneliness may serve as an early risk factor for later psychotic disorders and support its role as a potential target for preventive mental health interventions from an early age.

This may be especially relevant considering that childhood loneliness is a prevalent phenomenon that appears to be increasing in recent years.

This study offers valuable insight into the association between childhood loneliness and first-episode psychosis. With the rise of digitalisation and social isolation, loneliness has become a pervasive issue affecting young individuals.

The compelling findings of this study, which establish a direct connection between childhood loneliness and the onset of psychosis, highlight a concerning trend and underscore the importance of addressing social connectedness and emotional well-being from an early age,said Professor Andrea Fiorillo, President Elect of the European Psychiatric Association.

Author: Sarah Carter Source: European Psychiatric Association Contact: Sarah Carter European Psychiatric Association Image: The image is credited to Neuroscience News

Original Research: The findings will be presented at the 32nd European Congress of Psychiatry

Continued here:
Childhood Loneliness Linked to Later Psychosis - Neuroscience News

Anatomy

‘Grey’s Anatomy’: Meredith’s Family Emergency Brings Up the Past – PEOPLE

This post contains spoilers from the Thursday, April 11 episode of Grey's Anatomy.

A night of celebration turned to tragedy on Grey's Anatomy.

Several injured medical students were rushed to the hospital after a deck collapsed during a White Coat party. Everybody grab a chart, this is going to be a long night, Miranda Bailey (Chandra Wilson) told the interns.

Benson "Blue" Kwan (Harry Shum Jr.) and Simone Griffin (Alexis Floyd) accidentally lost track of a student named Eddie. When they still couldnt find him, a nurse told them that they saw him near the stairwell. The pair then found Eddie on the ledge of the rooftop.

When they tried to talk him down, Eddie responded that he wondered what would happen if he fell or not.

Read on to learn more about this week's episode of Grey's Anatomy.

Disney/Anne Marie Fox

Simone and Blue raced to help Eddie. After she asked if he was having thoughts of suicide, he responded, I guess. Sometimes. She reminded him that they were there if he wanted to talk. He then sat down on the ledge of the roof and said, It seems darker up here, the city.

He eventually admitted was overwhelmed by med school, telling the doctors, I think Im broken. I dont deserve this anymore. He later added, I dont know how to live with all the pressure and all the pain.

Blue then confided in the patient that he had experienced similar feelings, saying, Youre not alone and on most days, I dont feel like a doctorlet us get you some help. Blues words were enough to get him to step down from the ledge and come with them.

After the trying experience, Simone went to an on-call room to get some rest. Before she could fall asleep, Lucas Adams (Niko Terho) whom she was still avoiding after their romantic entanglement fell apart found her and she said, I had a really long night.

Ill go, he replied, but she then invited him to lay next to her in bed and he joined her.

ABC/Anne Marie Fox

Nick Marsh (Scott Speedman) told Meredith Grey (Ellen Pompeo) that he had rushed her son Bailey to the hospital in Boston with early appendicitis.

Meredith was upset then that Nick had taken Bailey to the hospital without her consent, saying, Tell Bailey I will be there as soon as I can before hanging up.

Richard Webber (James Pickens Jr.) then found Meredith and offered to help to call Catherine Avery (Debbie Allen).

Im his mother, you call me... call me immediately, Meredith insisted when Nick called back.

On the plane to Boston, Meredith admitted that she worried history would repeat itself with her son as her husband Derek Shepard (Patrick Dempsey) had died because surgeons didnt provide him with a timely CT scan following a major accident.

When Meredith arrived at the hospital, she coldly dismissed Nick, despite him rushing to get Bailey the care he needed. Of course, when Bailey woke up, he asked for Nick immediately.

Later, Meredith went to find Nick and told him that she was panicked about not being there for her kids. Im all they have," she said.

However, he reminded her that she has a village including him that loves and supports her children.

Ive been doing this a long time alone; it may take me a minute to adjust, she said. He responded, Ive got a minute.

Jo Wilson (Camilla Luddington) told her boyfriend Atticus "Link" Lincoln (Chris Carmack) she was late. He asked for what and she responded, My period.

She then got called to the emergency room and he asked her if they should stay to discuss her being late. Its a 9-1-1, Jo said. Link replied, So is this.

When Jo worried about how they would manage if she was pregnant, Link reminded her, Were in this together, no matter what.

Disney/Anne Marie Fox

Jo refused to look at the pregnancy test and Link was excited to inform her that it was negative. However, she was none too thrilled by his reaction especially when she realized the test was a dud.

Im not pregnant, she later told him. However, she admitted that the pregnancy scare had made her realize that she wanted to have a baby with him to add to their brood of her daughter Luna and his and Amelia Shepherds (Caterina Scorsone) son, Scout.

I can get there. Its just gonna take me some time, he responded.

Never miss a story sign up forPEOPLE's free daily newsletterto stay up-to-date on the best of what PEOPLE has to offer, from juicy celebrity news to compelling human interest stories.

Grey's Anatomyairs Thursdays at 9 p.m. ET on ABC.

If you or someone you know is considering suicide, please contact the 988 Suicide and Crisis Lifeline by dialing 988, text "STRENGTH" to the Crisis Text Line at 741741 or go to 988lifeline.org.

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'Grey's Anatomy': Meredith's Family Emergency Brings Up the Past - PEOPLE

Anatomy

Grey’s Anatomy: Cristina Yang’s Return Prospect Gets Honest Response From Sandra Oh – Screen Rant

Summary

Actor Sandra Oh has opened up about the possibility of her returning as Cristina Yang in Grey's Anatomy during a future episode. Oh debuted as Cristina in the show's first episode, continually being a major character throughout her time on the series. She eventually left the series at the end of season 10, after she accepts a job as head of a new hospital in Zrich, Switzerland. This gave Cristina a proper ending as she said goodbye to her fellow doctors.

Speaking with ET, Oh addressed how likely it would be for her to come back as Cristina in any upcoming episodes of the show, such as Grey's Anatomy season 21. The star said that, while she's grateful viewers want to see more of her on the series after all this time, she's satisfied with how her story ended and doesn't have plans to continue it. Check out what Oh had to say below:

I love that I love that people are still [fans]. I love that you asked me that, because Cristina Yang is, of course, near and dear to my heart. [But] I will say, not anytime soon, my love. I hope people feel like I did my job, which is that I brought to life a character and she had a growth over 10 seasons, and that it was true. She was ready to move on, and so have I.

Cristina's storyline in the series by becoming head of a hospital in Switzerland, reflects how driven and career-oriented she is while giving her a proper sendoff. While Oh herself hasn't returned as the doctor since departing, she was last seen portrayed by a body double at Derek's funeral in season 11. Season 16 also features text messages she sends to Meredith, leading to her meeting Cormac Hayes, who becomes a major character in the series for a few seasons.

Despite how much the character has continued to have a presence in the series, Oh's answer about not coming back signals her story arc will not continue. Cristina's storyline ended in a satisfactory place, as her new job means she can now pursue the medical career she wants. Her happy ending is coupled with the actor taking on a variety of exciting new roles, like appearing in the positively-received The Sympathizer. Because she's spent the last decade taking on roles beyond the medical franchise, her return seems unlikely to happen soon.

It's still possible Cristina could make a guest appearance in a later episode, with Oh briefly reprising her role despite the character's story being over. However, the chances of her coming back appear slim, even if she were to show up one last time at some point so viewers can learn what her life has been like since leaving the hospital. Although it seems her time on the show is permanently over, her contribution to Grey's Anatomy allowed for a stellar character to help define the drama's first decade.

Grey's Anatomy airs Thursdays on ABC.

Source: ET

Grey's Anatomy is considered one of the great television shows of our time, winning several awards and four Emmys. The high-intensity medical drama follows Meredith Grey and the team of doctors at Grey Sloan Memorial, who are faced with life-or-death decisions on a daily basis. They seek comfort from one another, and, at times, more than just friendship. Together they discover that neither medicine nor relationships can be defined in black and white.

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Anatomy

‘Grey’s Anatomy’ recap: Is Jo pregnant? – Entertainment Weekly News

Whats worse than a bunch of injured medical students overflowing the ER? A bunch of sloppy, drunk, injured, medical students acting annoying in the ER. Thats what you get when the second-floor deck collapses at a white coat party, and all the intoxicated people geek out diagnosing each other on Grey's Anatomy tonight.

As Yasuda (Midori Francis) figures out how to keep med students bodily fluids off of her in the pit, Adams (Niko Terho) searches for a bloodied lab coat, which will hopefully calm the spirits of his patient Sophie. Shes currently prepping for surgery since a rather large wooden beam is protruding from her back. Lo and behold, the medics cut her precious white coat off her body in the ambulance, and thats all Sophie can think about.

Adams locates the bloodied, shredded mess of a coat, and Sophie quickly transitions into being in a hospital is so cool mode until her stress levels rise again when she realizes she cant feel her right leg. Being the smart, educated medical student she is, Sophie knows this is very, very bad news. She begs Adams to do everything in his power to fix her.

Owen (Kevin McKidd) and Amelia (Caterina Scorsone) agree that spinal surgery is necessary, but they decide to just remove the wooden stake from her back, close her up, and see what happens. Its going to be a mess in there, and Amelia needs to know what shes working with before she promises Sophie will be able to walk, let alone stand.

But when Amelia opens her up and Owen un-stakes her, the situation miraculously becomes uncomplicated. Adams intervenes from the viewing galley intercom, imploring his aunt to perform surgery. Sophie later wakes up to a healed spine and a fresh, sparkling white lab coat, courtesy of Adams.

Disney/Anne Marie Fox

Im sure Meredith (Ellen Pompeo) would have been pulled in to help with the chaos had her son Bailey not been rushed to the hospital. For those of you just joining us, Meredith spends part of her time in Seattle trying to get funding for her Alzheimers research and the other part of the time with her kiddos and Nick (Scott Speedman) in Boston. You can imagine her anger when she receives a text from her daughter explaining that Nick took Bailey to the East Coast version of Grey Sloan Memorial.

Bailey has appendicitis, and Nick is handling it. Meredith is desperate to catch a flight to Boston so she can wring Nicks neck for not calling her sooner. Enter Richard (James Pickens Jr.) with his wifes private jet.

Meredith is so snippy with Nick on the phone as she rushes across the country to be with her boy. She becomes panicked that the doctor is going to screw up. Finally, everything becomes clear. Simple steps were missed with Derek. Meredith is afraid her son is going to fall into those same circumstances.

Thankfully, Bailey is fine, Meredith cools off, and she and Nick have a talk about how much he loves her kids and wants to be in their lives, even though Meredith is strong-willed and uber-independent. Meredith asks for a minute to adjust. Nick says he has all the minutes in the world. Could this guy be more perfect? Besides the fact that he didnt call Meredith immediately, I think not.

Sometimes, Meredith is so mean to Nick that it makes me want to give him a hug. Perhaps I should look into becoming a professional hugger like that lady who crawled up into the bed with Winston (Anthony Hill) and Millins (Adelaide Kane) patient to lower his blood pressure before surgery. There are weirder ways to make money, Im sure. Its worth researching.

Of course, Winston thinks the professional hugger is annoying, especially when she suggests they postpone surgery for a bit. He asks the human blanket to take a hike and demands Millin prep their patient for surgery. Millin smarts off to Winston, wondering out loud when the coolest doctor became so rude to both patients and residents. This did not go over well with Dr. Ndugu.

When their patient begins to spiral out of control on his way to the OR, Winstons tune changes, and he hops up onto the gurney to snuggle. Millin is impressed and tells her mentor after surgery. Winston admits that his personal life has infiltrated his workspace, and he promises not to let it happen again. Read: Maggie served him divorce papers. Ugh.

Disney/Anne Marie Fox

Meanwhile, back in the ER, Griffith (Alexis Floyd) and Kwan (Harry Shum Jr.) have lost one of the drunk med students and have to scour the hospital to find him before they are both fired. Someone mentioned that they saw him near the stairway to the roof. Griffith and Kwan find Eddie pacing on the ledge, holding his bright new coat. Griffith receives his lab results on her tablet and notices that he is not drunk. Eddie is depressed.

The pair calmly try and talk Eddie off the ledge and both are encouraged when he chooses to sit down. Griffith listens as Eddie works through his thoughts and feelings about becoming a doctor. Eddie doesnt think hes cut out for it. He doesnt know how to live with the pressure and pain.

Its shocking to hear Kwan, who has been silent up until this point, agree with Eddie. Kwan admits that he still doesnt feel like a doctor, but hes still here. He assures Eddie that he is not alone and asks for his hand so he can help him down from the ledge. He wants to get Eddie help.

Eddie turns, offers Kwan his hand, and allows the two interns to help him down. Later, Griffith offers to listen if Kwan needs to talk, but he dismisses her. She ends up in an on-call room snuggling with Adams. I guess these two are talking again. And who needs to hire professional huggers when you have ex-boyfriends to cuddle?

I should also inform you that Jo (Camilla Luddington) thought she was pregnant with Links (Chris Carmack) baby. While waiting for not one but two pregnancy tests, Jo and Link ran through every scenario of what it would look like to be parents to three children in diapers. Once the official test came back negative, they agreed to one day have a baby, but not now. Im confident that their baby will have amazing skin, teeth, and hair. Im just saying.

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'Grey's Anatomy' recap: Is Jo pregnant? - Entertainment Weekly News

Anatomy

Grey’s Anatomy’s Most Enduring Character Is a Real-Life Scrub Nurse – CBR – Comic Book Resources

Summary

BokHee, the longest-lasting supporting character of the cast of Grey's Anatomy, is played by an actual scrub nurse who certainly takes her role seriously. Actor Kathy C. An, also known as BokHee An, portrayed BokHee on both Grey's Anatomy and its six-season spinoff Private Practice. She has garnered a massive following among Grey's Anatomy fans, and for good reason she is undeniably one of the most dedicated actors on the show.

Designated as a "protect-at-all-costs" character by fans, Grey's Anatomy's BokHee has appeared in every season to date. She has very few speaking lines throughout the series, usually being spoken to by other characters rather than driving the narrative herself. She didn't actually talk until Season 10 when she recommended a bypass surgery for Alex's father in "Get Up, Stand Up." She spoke again in Season 15's "I Want a New Drug," praising Ellen Pompeo's Meredith Grey as "Wonder Woman." Aside from these two instances, BokHee largely communicates through facial expressions and reactions, often telling the main characters what they need to hear without saying a word.

Updated by Jordan Iacobucci on April 14, 2024: Grey's Anatomy has officially been renewed for its twenty-first season. Now bereft of its main character, Dr. Meredith Grey, the series is poised to take a new direction as its supporting cast fills the void left in Ellen Pompeo's wake. However, the actress has been confirmed to return in a recurring role in upcoming seasons. Nevertheless, while the series is always transforming itself, it is good for viewers to know that some things never change. In over twenty years of television, the supporting character Nurse BokHee has remained a fixture of Grey's Anatomy. Moreover, the actress's history in the medical profession adds some much-needed realism to the long-running medical drama.

Kathy C. An worked asa scrub nursein Los Angeles for 56 years before retiring in 2015. Before her retirement, actor Giacomo Gianniotto who played Andrew DeLuca from Season 11 through Season 17 watched a surgery in which An assisted to prepare for his part. Though it is yet unconfirmed, it's quite possible Gianniotto is not the only member of the Grey's Anatomy crew that has shadowed An in the decade she worked on Grey's Anatomy and was assisting in surgeries in Los Angeles. After all, many cast and crew members regularly watch real-life surgeries in the Los Angeles area to prepare for specific episodes and scenes that include those surgeries.

BokHee An adds to the authenticity of Grey's Anatomy just by being onscreen. Whether viewers consciously realize it, they can catch small details and tell whether they're fake. This is why Tom Cruise hangs out on actual airplanes when doing his stunts and CGI car chases aren't as appealing in action movies. An actor can train to play a nurse for as long as they want, but it's near-impossible to replicate the simple, natural, swift hand movements that only an experienced nurse has. BokHee is the only Grey's Anatomy cast member outside the show to have a medical career. Behind the camera, however, there are a few more medical professionals who help add to the show's authenticity.

Grey's Anatomy Ratings And Scores

Rotten Tomatoes Critics Score

Rotten Tomatoes Audience Score

International Movie Database

84%

73%

7.6/10

Grey's Anatomy may not be viewers' first idea regarding a strictly realistic procedural series, but it is far more realistic than audiences give it credit for. While the Shonda Rhimes-created show makes the occasional suspension of reality for storytelling, Grey's Anatomy isconsistently accurate,according to most medical professionals. Executive producers Zoanne Clack and Fred Einesman, both doctors, play a huge role in the fact-checking process. Many other real-life doctors and medical professionals are also brought on to advise and fact-check the work, often adding medical text to the scripts wherever the writer's room puts "medical medical."

Given her surgical background, having Kathy C. An star on Grey's Anatomy as a recurring character is a testament to the show's incredible attention to detail. Not only does it add to the medical drama's nuance, but it also makes BokHee an even more lovable character. Though it's unlikely BokHee will ever get her own Grey's Anatomy episode, knowing this information about Kathy C. An makes her appearances all the more entertaining. Even with her generally limited storyline in the series, BokHee's presence greatly elevates Grey's Anatomy, injecting a sense of realism into the series that other procedurals often lack.

Grey's Anatomy may not be strictly realistic in every regard, but its attempts to remain somewhat consistent with actual medical practices help it stand out from other medical dramas. The series understandably has to heighten some of its medical aspects to keep viewers engaged, but it at least makes an effort not to take things too far. In part, this has helped Grey's Anatomy remain popular for two decades.

While other medical procedural series like Chicago Med and New Amsterdam have found their audiences, no series of their genre holds a candle to the popularity of Grey's Anatomy. The series has transcended multiple decades with its high-stakes drama and memorable storylines, consistently drawing a passionate fanbase to each and every season. The series has even been able to weather the usually crippling loss of a beloved lead, suggesting that it is nowhere near its end.

For all of the extra work that must be done behind the scenes, the attention to detail in Grey's Anatomy's medical scenes greatly improves the overall series. Real-life professionals like Kathy C. An help keep the seriesgrounded in actual medical science, even if the personal relationships and storylines sometimes exit the realm of believability. So long as the series works to maintain a certain level of realism, it can expect to continue to enjoy a high level of popularity among audiences, even as it continues its twentieth season.

Grey's Anatomy is available to stream on Netflix and Hulu.

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Grey's Anatomy's Most Enduring Character Is a Real-Life Scrub Nurse - CBR - Comic Book Resources