How Mutations In A Suspect Gene May Give Rise To Autism, Schizophrenia

[AGXStarseed]

(Not written by me)

Recent advances in genomic technology have suggested that several hundred genes are likely involved as risk factors for neurodevelopmental disorders, such as autism and schizophrenia. These disorders arise from abnormalities that occur when the brain is still developing.

Now, scientists at the Salk Institute for Biological Studies in La Jolla, Calif., have pinpointed a gene linked to these disorders that seems to be crucial for normal brain structure in prenatal development. The findings, which appear in an open-access article in the Jan. 14 issue of Cell Reports, shed new light on the mechanistic workings of a gene called MDGA1, previously implicated in autism, schizophrenia and bipolar disorder.

Signs of these disorders often take years to manifest or may not show up until adolescence, young adulthood or even adulthood, and studying how certain genes function early in life may be able to aid drug discovery and the development of new treatments for autism and related disorders.

More than a decade ago, a Salk team led by molecular neurobiology professor Dennis O’Leary discovered MDGA1, which codes for a protein that influences neuronal migration in the developing brain. Migration is an important feature of development that happens to all types of cells that guides them from their birthplace to their final destination in the body.

The protein MDGA1 (red), which has been linked to autism, schizophrenia and bipolar disorder, is found in the areas of the brain (green) that give rise to new neurons. (Image courtesy of the Salk Institute for Biological Studies)


To better understand the role of MDGA1 and its relationships to the cerebral cortex and early brain development, the Salk team used an animal model to disable the gene in mice a little more than halfway through pregnancy. The researchers observed that this change disrupted typical neuronal migration and instead made the neuron precursor cells travel to the wrong places in the brain. The disabled MDGA1 gene caused the neuron precursor cells to die off before they could become fully formed neurons.

Without MDGA1, the study authors say the cerebral cortex loses about half its neurons, and this critical loss strongly hinders the ability of the cortex to communicate with other brain areas.

What the new results hint at is that mutations in the MDGA1 gene during early brain development of the cerebral cortex may lead to brain disorders later in life.

The Salk study was conducted in mice, so further research in humans is obviously necessary. But the findings are still intriguing, especially considering that a 2014 study in the New England Journal of Medicine found small patches of disorganized neurons in the cerebral cortices of children with autism. The authors of that study looked at post-mortem brain samples from 22 who died between the ages of 2 and 15. Half of the children had autism during their lifetime and half did not. In 10 of out 11 of the autistic brains, plus one from the unaffected group, investigators found abnormal spots in the cortex. Each varied slightly, but some had a specific layer missing and others had missing cells that should have been there.

Additional experiments conducted by the Salk group using animal models demonstrated that when MDGA1 is mutated rather than deactivated completely the change prevents neuron precursors from sticking to one another, an essential feature needed for these cells to divide and turn into neurons.

Of course, the research doesn’t end there. The Salk scientists plan to continue investigating MDGA1 in both early brain development and adulthood and evaluate how mice lacking the gene behave.

Emily Mullin is a DC-based science writer, focusing on health and medicine. Follow her at Forbes and on Twitter.



SOURCE: http://www.forbes.com/sites/emilymu...utism-schizophrenia/#2715e4857a0b62326ddd5fd0

 

[unsurewhattoname]

Signs of these disorders often take years to manifest or may not show up until adolescence, young adulthood or even adulthood

That must be talking about schizophrenia and bipolar, right? Autism needs to be present (or "show up") in the early development period. You can't suddenly start being autistic as an adult.

 

[Gingerpickles]

Yeah , Unsure something is fishy. Sounds like they are trying to consolidate disorders even tighter so they can be less generous with criteria of what constitutes a need for support.... Alzheimer's is hella more like "adult onset" autism than bipolar is. Most bipolar that have been in my life are people suffering from lithium imbalances and other identifiable chemical hiccups. And actually with a family of many with Asperger's, there are not incidences of any other "mental" disorders.


My son when tested genetically, has extra material in 14 as an anomaly and a heaping helping of the hfe. But otherwise was fairly predictable

 

[ancusmitis]

Without MDGA1, the study authors say the cerebral cortex loses about half its neurons, and this critical loss strongly hinders the ability of the cortex to communicate with other brain areas.

Half? That sounds like some pretty heavy stuff. I'm pretty sure that I've got more than half of the brain cells apportioned out to me.

 

[Beverly]

As bad as some of it sounds and, the correlations, I can see how missing neurons in the cerebral cortex could be at least a major factor in ASD. Take social skills for example, if you lack the neurons to transmit what you perceive in a social situation to the correct area of the brain for rapid interpretation, you are going to struggle with those skills as many of us do.

Exactly what the result of MDGA1 dysfunctions and/or mutations is would depend on exactly which neurons were missing or damaged so, I can see how it may be possible for it to be either responsible for or, a major contributing factor in a lot of different issues.

That would also help explain why some of us can adapt very well later in life, brains are capable of forming alternate pathways, especially if something is required frequently. Like socializing for me, it gets easier and easier for me as the years roll by and, I'm actually at the point od seeking out opportunities to socialize and, hosting social events because I wan to be social. My career demands that I be adept at socializing so, I devoted a lot of time and study to learning to do it well. Maybe my brain made alternate pathways to allow it to process social information better?

 

[Garry63]

(Not written by me) I have read that some research bodies in Europe want to designate Aspergers to a cluster A personality disorder. I suppose because they seem to see some underlying schizoid traits? who knows. Many of us seem to have contradictory features that causes the Shrink to shrink I think! As an example (warning! I'm about to talk about my self) I have Hashimoto's Thyroditis (my mother also) if I exercise to about 70pc maximum for a few days consecutively my T3 levels drop and I experience a mood disorders like Bipolar, when I increase my T3 intake I lapse into flights of speech, clanging, making faces at my self in the mirror and uttering odd noises. Between the two I have a sort of predominately obsessive thinking structure, neglect domestic matters and try to avoid shocking and repugnant thoughts. Bipolar? Schizophrenic? OCD? My Asperger's is not your Asperger's, but the powers that be are not paid to differentiate.
PS. Speaking of the typical 'traits' of Aspergers, I have read and understood the work's of Kant and Sartre but can't complete simple sums and grammar.


Recent advances in genomic technology have suggested that several hundred genes are likely involved as risk factors for neurodevelopmental disorders, such as autism and schizophrenia. These disorders arise from abnormalities that occur when the brain is still developing.

Now, scientists at the Salk Institute for Biological Studies in La Jolla, Calif., have pinpointed a gene linked to these disorders that seems to be crucial for normal brain structure in prenatal development. The findings, which appear in an open-access article in the Jan. 14 issue of Cell Reports, shed new light on the mechanistic workings of a gene called MDGA1, previously implicated in autism, schizophrenia and bipolar disorder.

Signs of these disorders often take years to manifest or may not show up until adolescence, young adulthood or even adulthood, and studying how certain genes function early in life may be able to aid drug discovery and the development of new treatments for autism and related disorders.

More than a decade ago, a Salk team led by molecular neurobiology professor Dennis O’Leary discovered MDGA1, which codes for a protein that influences neuronal migration in the developing brain. Migration is an important feature of development that happens to all types of cells that guides them from their birthplace to their final destination in the body.

The protein MDGA1 (red), which has been linked to autism, schizophrenia and bipolar disorder, is found in the areas of the brain (green) that give rise to new neurons. (Image courtesy of the Salk Institute for Biological Studies)


To better understand the role of MDGA1 and its relationships to the cerebral cortex and early brain development, the Salk team used an animal model to disable the gene in mice a little more than halfway through pregnancy. The researchers observed that this change disrupted typical neuronal migration and instead made the neuron precursor cells travel to the wrong places in the brain. The disabled MDGA1 gene caused the neuron precursor cells to die off before they could become fully formed neurons.

Without MDGA1, the study authors say the cerebral cortex loses about half its neurons, and this critical loss strongly hinders the ability of the cortex to communicate with other brain areas.

What the new results hint at is that mutations in the MDGA1 gene during early brain development of the cerebral cortex may lead to brain disorders later in life.

The Salk study was conducted in mice, so further research in humans is obviously necessary. But the findings are still intriguing, especially considering that a 2014 study in the New England Journal of Medicine found small patches of disorganized neurons in the cerebral cortices of children with autism. The authors of that study looked at post-mortem brain samples from 22 who died between the ages of 2 and 15. Half of the children had autism during their lifetime and half did not. In 10 of out 11 of the autistic brains, plus one from the unaffected group, investigators found abnormal spots in the cortex. Each varied slightly, but some had a specific layer missing and others had missing cells that should have been there.

Additional experiments conducted by the Salk group using animal models demonstrated that when MDGA1 is mutated rather than deactivated completely the change prevents neuron precursors from sticking to one another, an essential feature needed for these cells to divide and turn into neurons.

Of course, the research doesn’t end there. The Salk scientists plan to continue investigating MDGA1 in both early brain development and adulthood and evaluate how mice lacking the gene behave.

Emily Mullin is a DC-based science writer, focusing on health and medicine. Follow her at Forbes and on Twitter.



SOURCE: http://www.forbes.com/sites/emilymu...utism-schizophrenia/#2715e4857a0b62326ddd5fd0