Insight into the genetics of autism offers hope for new drug treatments


Date:
February 10, 2022
Source:
Lancaster University
Summary:
Drugs to increase insulin signaling may be effective for treating
autism, say researchers who have discovered how a genetic change
impacts on insulin signaling and glucose metabolism in the brain.



FULL STORY ========================================================================== Drugs to increase insulin signaling may be effective for treating autism
say Lancaster University researchers, who have discovered how a genetic
change impacts on insulin signaling and glucose metabolism in the brain.


==========================================================================
In the human genome small sections of DNA have been found to be duplicated
or deleted in some people, a phenomenon known as Copy Number Variation.

Some of these genetic changes cause neurodevelopmental problems and dramatically increase someone's risk of developing disorders such as
autism, schizophrenia and Tourette's syndrome.

For example, people with a DNA deletion at chromosome 2p16.3, which
results in deletion of the Neurexin1 gene, commonly experience neurodevelopmental delay and cognitive problems.

People with the 2p16.3 deletion are also around 14 to 20 times more likely
to develop neurodevelopmental disorders including autism, schizophrenia
and Tourette's syndrome than people without the deletion.

There are an estimated two to three million people worldwide who have
this type of DNA deletion but there are currently no effective drug
treatments for their resulting cognitive problems.



==========================================================================
For the first time, in research funded by The Royal Society, scientists
have demonstrated that Neurexin1 gene deletion reduces glucose
metabolism in the prefrontal cortex, a key brain region involved in higher-level cognitive functions including cognitive flexibility and
paying attention. Neurexin1 deletion was also found to reduce insulin
receptor signaling in the prefrontal cortex, which likely underlies the
reduced glucose metabolism seen in this region.

The research, published in the journal Autism Research, give valuable
new insight into how this leads to cognitive deficits, behavioural
changes and dramatically increases the risk of developing a range of neurodevelopmental disorders.

The key finding that Neurexin1 deletion impacts on insulin signaling and glucose metabolism in the prefrontal cortex suggests that using drugs
to increase insulin signaling may be an effective therapeutic strategy.

Lead researcher Dr Neil Dawson from Lancaster University said: "There
is an urgent need to further understand the underlying neurobiology of neurodevelopmental disorders in order to develop new treatments. Drugs
to help people with their cognitive and social problems are particularly urgently needed, as these symptoms dramatically impact on their quality
of life." In addition, the researchers also showed that Neurexin1
deletion causes deficits in cognitive functions that depend on the
prefrontal cortex, including a deficit in the ability to be flexible.

The research also found that the reduced glucose metabolism in the
prefrontal cortex that results from Neurexin1 deletion was linked with
being hyperactive when experiencing novel situations.

A second brain region identified as being impacted by Neurexin1 deletion
was the dorsal raphe', which showed increased activity. This region is the origin of serotonin neurons that project throughout the brain, suggesting
that Neurexin1 deletion also makes the serotonin neurotransmitter system dysfunctional.

Dr Neil Dawson said: "In addition, the observation that the
serotonin system may be dysfunctional requires further research,
and suggests that drugs targeting this neurotransmitter system may
also be useful. We can now test the ability of drugs that target
these mechanisms to restore these translational changes seen as part
of ongoing research to develop better treatments for people with
2p16.3 deletion, autism, schizophrenia and Tourette's syndrome."
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by Lancaster_University. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Rebecca B. Hughes, Jayde Whittingham‐Dowd, Steven J. Clapcote,
Susan J. Broughton, Neil Dawson. Altered medial prefrontal
cortex and dorsal raphe' activity predict genotype and
correlate with abnormal learning behavior in a mouse model of
autism‐associated 2p16.3 deletion. Autism Research, 2022;
DOI: 10.1002/aur.2685 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220210114109.htm

--- up 9 weeks, 5 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)