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"If we were to use drugs that mimic the
actions of nicotine at an early time in human brain development, would we begin
to help those and other circuits develop properly and thus significantly
mitigate the deficits in autism? This is a novel way of thinking about how we
might be able to use drugs to approach autism treatment," said Rene Anand,
associate professor of pharmacology in Ohio State University's College of
Medicine and principal investigator of the research.
"It would not be a complete cure, but right now we know very little and
have no drugs that tackle the primary causes of autism."
The drugs in question are known as cholinergic agents, which interact with the
brain to counter nicotine addiction. Anand said the medications could be
retailored for use in children in an effort to increase the level of neurexin-1
beta protein in the brains of people with autism.
More neurexin would in turn not only enhance the presence of nicotinic
acetylcholine receptors, but also a host of other proteins that are important
for the proper formation and maturation of synapses. Proper synapse function is
critical to the nervous system's ability to connect to and control other systems
of the body.
"Now that these associations have been made, we believe that nicotine in
smokers' brains possibly increases the level of neurexin-1 and, as a
consequence, helps bring more receptors to the synapses and makes those circuits
highly efficient, reinforcing the addiction. In autism, we have the opposite
problem. We have a lack of these receptors, and we speculate that neurexin
levels are lower," he said.
Anand presented the research Monday (11/17) at the Society for Neuroscience
meeting in Washington, D.C.
Autism symptoms include impaired social interaction, problems with verbal and
nonverbal communication, and repetitive or severely limited activities and
interests. An estimated three to six of every 1,000 children are diagnosed with
autism, and boys are four times more likely than girls to have the disorder,
according to the National Institute of Neurological Disorders and Stroke.
Anand and colleagues were studying drug abuse and addiction when they discovered
the neurexin-1 beta protein's relationship to a certain type of nicotinic
receptor. The timing of the discovery was key, as it built upon two other
research groups' previous observations: The brains of people with autism and
other neurological disorders that were examined after their death showed a
60-percent to 70-percent decrease in specific nicotinic receptors, and some
patients with autism have mutations in the neurexin-1 gene that suggest the
gene's improper functions could play a role in the disorder.
"These have all been 'association studies.' None has been able to prove
what causes autism," Anand said. "And then we accidentally discovered
that neurexin-1 and nicotinic receptors tangle. So we knew that there was a
genetic link to the process leading to synapse formation, and we had nicotinic
receptors that had disappeared in the brains of autistic patients. Our finding
filled a gap by saying there is a physical and functional association between
these two things occurring in the brain."
Neurexin has implications for tobacco addicts, as well, Anand said. Yet another
group of researchers recently found that people with a mutation in the
neurexin-1 gene were more likely to be smokers, meaning changes in the gene's
functions that lead to excess levels of the nicotinic receptors might make
people more susceptible to nicotine addiction.
"Our research reveals how changes in the functions of neurexin could affect
the guidance of nicotinic acetylcholine receptors to their functional
destinations in nerve cells, perhaps increasing receptors in tobacco addicts
while decreasing them in autistic individuals, thus increasing susceptibility to
these devastating neurological disorders," Anand said.
The finding also has implications for nicotine addiction because drugs known to
alter neurexin's guidance of nicotinic receptors within nerve cells could be
used to suppress tobacco addiction.
This work is partially funded by the National Institite on Drug Abuse, the
National Alliance for Resarch on Schizophrenia and Depression, and by an OSU
Medical Center Research Day Travel Award.
Coauthors of the study are Stephanie Amici and Susan McKay of Ohio State's
Department of Pharmacology; Shi-Bin Cheng, Xiao-Qin Ren, Magdalen Treuil and Jay
Rao of the Louisiana State University Health Sciences Center in New Orleans; and
Jon Lindstrom of the University of Pennsylvania.
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