Bullying by childhood peers leaves a trace that can change the expression of a gene linked to mood

A recent study by a researcher at the Centre for Studies on Human Stress (CSHS) at the Hôpital Louis-H. Lafontaine and professor at the Université de Montréal suggests that bullying by peers changes the structure surrounding a gene involved in regulating mood, making victims more vulnerable to mental health problems as they age. The study published in the journal Psychological Medicine seeks to better understand the mechanisms that explain how difficult experiences disrupt our response to stressful situations. “Many people think that our genes are immutable; however this study suggests that environment, even the social environment, can affect their functioning. This is particularly the case for victimization experiences in childhood, which change not only our stress response but also the functioning of genes involved in mood regulation,” says Isabelle Ouellet-Morin, lead author of the study.

A previous study by Ouellet-Morin, conducted at the Institute of Psychiatry in London (UK), showed that bullied children secrete less cortisol—the stress hormone—but had more problems with social interaction and aggressive behaviour. The present study indicates that the reduction of cortisol, which occurs around the age of 12, is preceded two years earlier by a change in the structure surrounding a gene (SERT) that regulates serotonin, a neurotransmitter involved in mood regulation and depression.

To achieve these results, 28 pairs of identical twins with a mean age of 10 years were analyzed separately according to their experiences of bullying by peers: one twin had been bullied at school while the other had not. “Since they were identical twins living in the same conditions, changes in the chemical structure surrounding the gene cannot be explained by genetics or family environment. Our results suggest that victimization experiences are the source of these changes,” says Ouellet-Morin. According to the author, it would now be worthwhile to evaluate the possibility of reversing these psychological effects, in particular, through interventions at school and support for victims.

(Image: mentalhealthsupport.co.uk)

Evolution: It’s all in how you splice it

MIT biologists find that alternative splicing of RNA rewires signaling in different tissues and may often contribute to species differences.

When genes were first discovered, the canonical view was that each gene encodes a unique protein. However, biologists later found that segments of genes can be combined in different ways, giving rise to many different proteins.

This phenomenon, known as alternative RNA splicing, often alters the outputs of signaling networks in different tissues and may contribute disproportionately to differences between species, according to a new study from MIT biologists.

After analyzing vast amounts of genetic data, the researchers found that the same genes are expressed in the same tissue types, such as liver or heart, across mammalian species. However, alternative splicing patterns — which determine the segments of those genes included or excluded — vary from species to species.

“The core things that make a heart a heart are mostly determined by a heart-specific gene expression signature. But the core things that make a mouse a mouse may disproportionately derive from splicing patterns that differ from those of rats or other mammals” says Chris Burge, an MIT professor of biology and biological engineering, and senior author of a paper on the findings in the Dec. 20 online edition of Science.

Lead author of the paper is MIT biology graduate student Jason Merkin. Other authors are Caitlin Russell, a former technician in Burge’s lab, and Ping Chen, a visiting grad student at MIT.

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Brake on nerve cell activity after seizures discovered

Given that epilepsy impacts more than 2 million Americans, there is a pressing need for new therapies to prevent this disabling neurological disorder. New findings from the neuroscience laboratory of Mark S. Shapiro, Ph.D., at The University of Texas Health Science Center at San Antonio, published Dec. 20 in the high-impact scientific journal, Neuron, may provide hope.

“A large fraction of epilepsy sufferers cannot take drugs for their disorder or the existing drugs do not manage it,” said Dr. Shapiro, professor of physiology in the School of Medicine. “As a result, many opt for surgery to remove the hippocampus, a part of the brain where memories are stored but also where seizures are often localized. The heart-wrenching choice is between their memories and the epilepsy.”

Genes go into action
A major finding of the study is that selected genes get switched on during and after a seizure, sending swarms of signals to reduce uncontrolled firing of nerve cells. A medication that amplifies this response after a person’s initial seizure could thus prevent recurrent seizures and the onset of devastating epilepsy.

Uncontrolled electrical activity by specialized electricity-producing proteins in the brain called “ion channels” triggers epileptic seizures. One in 10 people have a lifetime risk of suffering a seizure, which can occur for a variety of reasons including traumatic brain injury, stroke or drug overdoses.

A powerful brake
Although not all seizures lead to epilepsy, some trigger changes in the brain that heighten the risk of the disorder. Dr. Shapiro’s research sheds light on why most isolated seizures do not lead to full-blown epilepsy, whereas others do. An ion channel called the “M-channel” acts as a powerful “brake” on hyper-excitability in the brain. Another organizational protein, called AKAP79, acting much like an air-traffic controller, calls in more M channels as part of neuroprotective response machinery.

Pharmacological therapy to enhance M-channel gene expression or AKAP79 function “could jump-start this neuroprotective mechanism to prevent a seizure from turning into epilepsy,” Dr. Shapiro said. “Administering it right after a traumatic brain injury could be very effective.”

It was not known that electrical activity could regulate M-channel genes, Dr. Shapiro said. Nor was it known that the AKAP79 organizer protein, which coordinates many aspects of M-channel function, could turn on their genes in a person’s DNA. By increasing M-channel expression in the brain, uncontrolled electrical firing of nerve cells in the brain is sharply controlled.

Mouse experiments
The Shapiro lab team records electrical currents and performs imaging in living nerve cells to measure M-channel activity. This study included inducing seizures in healthy mice. After a seizure, gene expression of M-channels in the hippocampus increased more than 10-fold within 24 hours, Dr. Shapiro said. This protective effect was completely absent in mice lacking the mouse version of the AKAP79 gene.

“Because excessive firing of nerve cells is also involved in chronic pains, such as migraines, mood disorders and hypertension, increasing M-channel signals to reduce nerve-cell firing could also likely be effective in treating those conditions,” Dr. Shapiro said.

Two heads are better than one

Dramatic expansion of the human cerebral cortex, over the course of evolution, accommodated new areas for specialized cognitive function, including language. Understanding the genetic mechanisms underlying these changes, however, remains a challenge to neuroscientists.

A team of researchers in Japan, led by Hideyuki Okano of Keio University School of Medicine and Tomomi Shimogori of the RIKEN Brain Science Institute, has now elucidated the mechanisms of cortical evolution. They used molecular techniques to compare the gene expression patterns in mouse and monkey brains. 

Using the technique called in situ hybridization to visualize the distribution of mRNA transcripts, Okano, Shimogori and their colleagues examined the expression patterns of genes that are known to regulate development of the mouse brain. They compared these patterns to those of the same genes in the brain of the common marmoset. They found that most of the genes had similar expression patterns in mice and marmosets, but that some had strikingly different patterns between the two species. Notably, some areas of the visual and prefrontal cortices showed expression patterns that were unique to marmosets. 

The researchers also found differences in gene expression within regions that connect the prefrontal cortex and hippocampus, a structure that is critical for learning and memory.