Gene Mutation Linked to Autism Found to Overstimulate Brain Cells

Brain Energy Electric Activity

Autism, also known as Autism Spectrum Disorder (ASD), is a complex developmental disorder that affects communication, social interaction, and behavior. It is characterized by difficulties in verbal and nonverbal communication, social interactions, and repetitive behaviors.

A new study led by Rutgers University has highlighted the potential of innovative techniques in understanding and studying mental disorders.

A new study led by scientists at Rutgers University has uncovered new insights into the underlying brain mechanisms of autism spectrum disorder (ASD). The study, which spanned seven years, found that a specific gene mutation known to be associated with ASD causes an overstimulation of brain cells that is significantly higher than in brain cells without the mutation.

The research team used cutting-edge techniques, including growing human brain cells from stem cells and transplanting them into mouse brains, to make these discoveries.

The work illustrates the potential of a new approach to studying brain disorders, scientists said.

Describing the study in the journal, Molecular Psychiatry, researchers reported a mutation – R451C in the gene Neurologin-3, known to cause autism in humans – was found to provoke a higher level of communication among a network of transplanted human brain cells in mouse brains. This overexcitation, quantified in experiments by the scientists, manifests itself as a burst of electrical activity more than double the level seen in brain cells without the mutation.

“We were surprised to find an enhancement, not a deficit,” said Zhiping Pang, an associate professor in the Department of Neuroscience and Cell Biology in the Child Health Institute of New Jersey at Rutgers Robert Wood Johnson Medical School and the senior author on the study. “This gain-of-function in those specific cells, revealed by our study, causes an imbalance among the brain’s neuronal network, disrupting the normal information flow.”

The interconnected mesh of cells that constitutes the human brain contains specialized “excitatory” cells that stimulate electrical activity, balanced by “inhibitory” brain cells that curtail electrical pulses, Pang said. The scientists found the oversized burst of electrical activity caused by the mutation threw the mouse brains out of kilter.

Autism spectrum disorder is a developmental disability caused by differences in the brain. About 1 in 44 children have been identified with the disorder, according to estimates from the Centers for Disease Control and Prevention.

Studies suggest autism could be a result of disruptions in normal brain growth very early in development, according to the National Institutes of Health’s National Institute of Neurological Disorders and Stroke. These disruptions may be the result of mutations in genes that control brain development and regulate how brain cells communicate with each other, according to the NIH.

“So much of the underlying mechanisms in autism are unknown, which hinders the development of effective therapeutics,” Pang said. “Using human neurons generated from human stem cells as a model system, we wanted to understand how and why a specific mutation causes autism in humans.”

Researchers employed CRISPR technology to alter the human stem cells’ genetic material to create a line of cells containing the mutation they wanted to study, and then derived human neuron cells carrying this mutation. CRISPR, an acronym for clustered regularly interspaced short palindromic repeats, is a unique gene-editing technology.

In the study, the human neuron cells that were generated, half with the mutation, half without, were then implanted in the brains of mice. From there, researchers measured and compared the electrical activity of specific neurons employing electrophysiology, a branch of physiology that studies the electrical properties of biological cells. Voltage changes or electrical current can be quantified on a variety of scales, depending on the dimensions of the object of study.

“Our findings suggest that the NLGN3 R451C mutation dramatically impacts excitatory synaptic transmission in human neurons, thereby triggering changes in overall network properties that may be related to mental disorders,” Pang said. “We view this as very important information for the field.”

Pang said he expects many of the techniques developed to conduct this experiment to be used in future scientific investigations into the basis of other brain disorders, such as schizophrenia.

“This study highlights the potential of using human neurons as a model system to study mental disorders and develop novel therapeutics,” he said.

Reference: “Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism” by Le Wang, Vincent R. Mirabella, Rujia Dai, Xiao Su, Ranjie Xu, Azadeh Jadali, Matteo Bernabucci, Ishnoor Singh, Yu Chen, Jianghua Tian, Peng Jiang, Kevin Y. Kwan, ChangHui Pak, Chunyu Liu, Davide Comoletti, Ronald P. Hart, Chao Chen, Thomas C. Südhof and Zhiping P. Pang, 24 October 2022, Molecular Psychiatry.
DOI: 10.1038/s41380-022-01834-x

The study was funded by the Robert Wood Johnson Foundation, the Governor’s Council for Medical Research and Treatment of Autism, and the National Institute of Mental Health.

9 Comments on "Gene Mutation Linked to Autism Found to Overstimulate Brain Cells"

  1. Calling this a “gin of function” is highly misleading and irresponsible scientific presentation in a growing field of work!

    • Calling this a “gain of function” is highly misleading and irresponsible scientific presentation in a growing field of work!

  2. Hanygem Bardago | January 14, 2023 at 1:58 am | Reply

    My eldest and only son has non verbal autism spectrum disorder. His pediatrician administered oxygen 30 minutes after birth

  3. I know that autism is passed down but I’m just getting p!ss*d and overly done with all this s&*t about Tylenol or baby food being linked to autism who ever came up with this hair brained idea to make a law suit needs to get a real job or start going after your states that’s putting up with old nasty d!*ks that think it’s their right to like babies for nasty reasons and pedos I personally don’t care if it’s a hate crime but I say take all of those stick f@*ks and send them to fight wars for free and not get paid so if they get blown up no big loss

  4. I’m 70. I was labeled shy when young. I couldn’t talk to people when someone talked to me,it scrambled my brain I couldn’t respond my head turned red instead, it ruined my life.i was labeled bi-polar. I’ve taken autism tests from internet. Bingo! Me to a T!

  5. Not genetic but epigenetic. Besides, china already has researched this… It is caused by immune response in the pregnant mother. The child’s brain is in a constant state of emergency, or more correctly, a constant state of immune response. This has been known for at least 7 years.

  6. Debra de la-Nougerede | January 14, 2023 at 2:18 pm | Reply

    Nothing to do with the assault of Alluminuim and Therimisol (mercury) crossing the young blood brain barrier due to polysorbate 80 in vaccines particularly the mmr then? Oh, and nothing to do with the global roll out of the mmr in 1987 just after major vaccine companies got themselves legally exempt from parental prosecution? When autism was 1 in 60 thousand, back in 1989, and a tsunami of asd happened as more and more vaccines were used on very young children. When ‘Autism’ is actually listed as a side effect in Merck’s side effects sheet provided to drs ,but not to parents? Of course being 1in 44 now is all due to all those autistic people breeding like rabbits isnt it!. What a load of money spinning BS ! Vast amounts of money to be made on the backs of Autism;it has been since the mid 80’s. Big pharma created a whole new generation of lives destroyed and ‘ research/drug sales potential’. But NO ONE DARE TALK ABOUT THE BLEEDING ELEPHANT IN THE ROOM! You people make me utterly sick! Ask drs how much blood money they’ve made by NOT showing parents side effects sheets, or how many pharma executives were employed to falsify ‘ trials’. Every single one of these people have sold their souls by harming babies irreparably, and damaged beyond hope hundreds of thousands of lives. Dont bother retorting with some brainwashed crap, iv been there done that, where autism is concerned for 34 years, dealt with the profiteers, crooks, know it alls, bullshters, climbers, liars, the whole lot! People have made FORTUNES, off riding on the backs of those theyve made autistic…and NO, before some smart adse says it…its not just better diagnosis. Pushing out ‘new reasearch’! Some genes are more susceptible to assault, just like very fair people are more prone to sun burn! That doesn’t mean their genes burn them! The outside assault of the SUN does, just like the mmr heavy metals assaults the brain! . You soul sold profiteers make me sick. All Hell bound. 🤬🤬🤬

  7. No surprise it isn’t a deficit here. As an autistic person I am constantly overstimulated and this causes all sorts of issues. I can say though it means I notice a lot of things others don’t and I am able to focus very fiercely if needed.

  8. I am not a scientist, but I am autistic and vaccines do not cause autism. Never have, never will and anyone – including commenters here – that say otherwise are complete idiots. Your kid is autistic because that’s how they were born. Stop blaming vaccines. That implies that the child was somehow ‘broken’ by a vaccine which is a huge stigma for the kid. How do you think it feels when a parent insists that medicine hurt you and now you are damaged goods?
    Your kid isn’t broken. They’re not damaged. They’re autistic. They were born that way. Instead of parents crying that someone else damaged your kid, accept them, help them and love them. Don’t make them feel broken by crying about bogus, disproven and 100% unscientific BS you read somewhere on the internet.
    Autism is not a disease, it’s not something that can be caught, it’s not something that can suddenly happen to someone. You’re born that way. We need accommodation, not some idiotioc lunatic telling us a vaccine broke us.

Leave a comment

Email address is optional. If provided, your email will not be published or shared.