Nav: Home

Looking behind a rare brain disease for clues to treat more common mental disorders

February 15, 2019

Researchers have clarified, for the first time, the mechanism behind a very rare brain disorder called MICPCH (microcephaly, disproportionate pontine and cerebellar hypoplasia) syndrome in animal models. Information gleaned from this study could also inform research into other, more common neurological diseases such as mental retardation, epilepsy, and autism.

MICPCH has only affected a total of 53 females and seven males worldwide so far. It is characterized by several developmental symptoms including small head size, slowed growth, cognitive delays, epilepsy, seizures, vision and hearing problems, decreased muscle tone, and autism. MICPCH is linked to irregularities, or mutations, on the X-chromosome that eventually lead to the chromosome's inactivation.

The study was published in the January 4th, 2019 edition of the journal Molecular Psychiatry.

Brain cells, or neurons, constantly communicate by sending messages to one another. There are two types of neurons in the brain: those that increase activity in other cells (excitatory neurons) and those that decrease it (inhibitory neurons). The mechanism behind keeping the balance between excitation and inhibition in the brain is very similar to that of a thermostat that is used to maintain a balanced temperature in a home. This mechanism is important because imbalances between excitation and inhibition can cause several serious disorders such as epilepsy and autism. One of the most important molecules that maintains the balance between excitation and inhibition is a protein found within the outer membrane of neurons, called the calcium/calmodulin-dependent serine protein kinase (CASK). Mutations in the gene that produce CASK therefore lead to several neurodevelopmental disorders such as mental retardation. A lack of the protein in the brain has been found to cause MICPCH syndrome.

"The aim of the study was to understand the pathophysiology of CASK-deficiency disorders in females, such as MICPCH syndrome, which are supposed to be influenced by X-chromosome inactivation," said corresponding author Katsuhiko Tabuchi, a professor in the Department of Molecular and Cellular Physiology at the Institute of Medicine, Academic Assembly at Shinshu University in Nagano, Japan.

However, the details of CASK-deficiency consequences have thus far been difficult to study, as mice that completely lack the protein die before they are developed enough to study.

In order to understand the mechanism behind the CASK-deficiency, researchers at Shinhsu University in Japan and Kafr Elsheikh University in Egypt have used gene manipulation techniques that shut off the CASK gene through X-chromosome inactivation in female mice without lethal consequences.

They found that neurons that lack CASK have a disrupted excitation and inhibition balance. They also found that this is because of a decrease in concentration of a specific receptor on the membrane that receives signals from other neurons. When the receptor concentration was increased, the excitatory and inhibitory balance was restored again, leading the researchers to believe that the receptor plays a central role in the mechanism in CASK-deficient neurons.

In the future, the researchers hope to address the effects of a CASK-deficiency in even greater detail by looking at its effects on the neural circuitry. "We hope to highlight the effect of two different types of neurons in one brain as well as the pathophysiology of CASK-deficiency disorders at neural circuit levels," professor Tabuchi adds.
-end-
The study was supported by a Grant-in-Aid for Young Scientists grant, several Grant-in-Aid for Scientific Research grants, several Grant-in-Aid for challenging Exploratory Research grants, the Foundation of Growth Science, the Japan Epilepsy Research Foundation, the Takeda Science Foundation, the Uehara Memorial Foundation, the Ichiro Kanehara Foundation, and the JST PRESTO Program: Development and Foundation of Neural Networks.

About Shinshu University

Shinshu University is a national university in Japan founded in 1949 and working on providing solutions for building a sustainable society through interdisciplinary research fields: material science (carbon, fiber, composites), biomedical science (for intractable diseases, preventive medicine), and mountain science. We aim to boost research and innovation capability through collaborative projects with distinguished researchers from the world. For more information, please see: https://www.shinshu-u.ac.jp/english/

Shinshu University

Related Autism Articles:

Genes, ozone, and autism
Exposure to ozone in the environment puts individuals with high levels of genetic variation at an even higher risk for developing autism than would be expected just by adding the two risk factors together, a new analysis shows.
A blood test for autism
An algorithm based on levels of metabolites found in a blood sample can accurately predict whether a child is on the autism spectrum of disorder (ASD), based upon a recent study.
New form of autism found
Autism spectrum disorders (ASD) affect around one percent of the world's population and are characterized by a range of difficulties in social interaction and communication.
Autism Speaks MSSNG study expands understanding of autism's complex genetics
A new study from Autism Speaks' MSSNG program expands understanding of autism's complex causes and may hold clues for the future development of targeted treatments.
Paths to Autism: One or Many?
A new report in Biological Psychiatry reports that brain alterations in infants at risk for autism may be widespread and affect multiple systems, in contrast to the widely held assumption of impairment specifically in social brain networks.
More Autism News and Autism Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#534 Bacteria are Coming for Your OJ
What makes breakfast, breakfast? Well, according to every movie and TV show we've ever seen, a big glass of orange juice is basically required. But our morning grapefruit might be in danger. Why? Citrus greening, a bacteria carried by a bug, has infected 90% of the citrus groves in Florida. It's coming for your OJ. We'll talk with University of Maryland plant virologist Anne Simon about ways to stop the citrus killer, and with science writer and journalist Maryn McKenna about why throwing antibiotics at the problem is probably not the solution. Related links: A Review of the Citrus Greening...