Scientists Discover Possible Way to Prune Extra Synapses In Autism

NrCAM protein may be key to pruning extra synapses and treating autism

There has been a lot of exciting research published in the past few months about the autistic brain and genes. The latest discovery comes from the University of North Carolina School of Medicine, and could lead to the development of new medications and therapies for the treatment of autism spectrum disorders (ASD).

The UNC study, lead by Patricia Maness, PhD and professor of biochemistry and biophysics, found that knocking out the gene NrCAM increases the number of dendritic spines on excitatory pyramidal neurons, which earlier studies have concluded results in too many synaptic connections that have been strongly linked to autism. In plain speak; scientists discovered a gene that influences the development of certain extra connections in the brain that make autistic brains function differently than others.

“Basic science in autism is converging in really exciting ways,” Maness said. “Too many spines and too many excitatory connections that are not pruned between early childhood and adolescence could be one of the chief problems underlying autism. Our goal is to understand the molecular mechanisms involved in pruning and find promising targets for therapeutic agents.” 

This study comes on the heels of a study from Columbia University that found an overabundance of the protein MTOR in mice bred with a rare form of autism. They used a drug to limit the mice’s MTOR, which decreased the dendritic spines, thus pruning the extra synapses, resulting in a significant decrease in the social behaviors associated with autism. This drug causes serious side effects, however, and will not become a viable treatment for autism. Also, the location of MTOR protein inside cells makes it particularly difficult to target. 

It isn’t yet known whether or not NrCAM and MTOR are linked, but Maness is now moving on to determine whether the decreased NrCAM protein can activate the MTOR protein. If so, the NrCAM protein may be a viable target for autism therapy, as it is much more accessible than MTOR. 

The UNC study published in The Journal of Neuroscience found that the NrCAM protein works with two other molecules to form a receptor on the excitatory pyramidal neurons that allows dendritic spines to retract and all those excess synapses can be pruned to allow brain circuits to function properly. 

“There are many genes involved in autism, but we’re now finding out exactly which ones and how they’re involved,” continued Maness. “Knowing that NrCAM has this effect on dendrites allows us to test potential drugs, not only to observe a change in behaviors linked to autism, but to see if we can improve dendritic spine abnormalities, which may underlie autism.”

This entry was posted in Autism Research and tagged , , . Bookmark the permalink. Post a comment or leave a trackback: Trackback URL.

Post a Comment

Your email is never published nor shared.

You may use these HTML tags and attributes <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>