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Published on: February 11, 2019
Cholinergic abnormalities in autism: is there a rationale for selective nicotinic agonist interventions?
Stephen I Deutsch1, Maria R Urbano, Serina A Neumann
1Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507-1912, USA. deutscsi@evms.edu
Clinical Neuropharmacology
|March 2, 2010
Summary
Investigating acetylcholine receptors in autism spectrum disorder (ASD) may reveal therapeutic targets. Targeting nicotinic acetylcholine receptors could potentially improve attention, cognition, and memory in individuals with ASD.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Disorders
Background:
- Autism spectrum disorders (ASD) involve core deficits in socialization, communication, and repetitive behaviors.
- Common comorbidities include intellectual impairment and epilepsy.
- Previous studies suggest alterations in cholinergic nuclei and acetylcholine receptors (AChRs) in the brains of individuals with ASD.
Purpose of the Study:
- To explore the potential therapeutic effects of selective cholinergic interventions for core autism spectrum disorder dysfunctions.
- To investigate the role of nicotinic acetylcholine receptors (nAChRs) in attention, cognition, and memory within the context of ASD.
- To examine the hypothesis that stimulating alpha7 nAChRs could restore inhibitory tone in the brains of individuals with ASD.
Main Methods:
- Review of existing data on cholinergic system involvement in ASD.
- Analysis of electrophysiological data related to seizure disorders in ASD.
- Conceptual exploration of pharmacological interventions targeting nAChRs.
Main Results:
- Findings from postmortem studies on cholinergic nuclei and nAChRs in ASD are limited and may reflect confounding factors.
- Electrophysiological data suggest an imbalance in excitatory and inhibitory tone in ASD brains.
- Alpha7 nAChRs are located on GABA inhibitory neurons, suggesting a potential mechanism for restoring inhibitory tone.
Conclusions:
- Selective cholinergic interventions targeting nAChRs warrant exploration for therapeutic benefits in ASD.
- Development of nAChR agonists, partial agonists, and positive allosteric modulators could facilitate clinical trials.
- Targeting nAChRs may offer a novel approach to address core symptoms and comorbidities in autism spectrum disorder.
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