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A significant reduction in the expression levels of a specific type of receptor called nicotinic acetylcholine receptors has been reported in post mortem brains of autistic patients. In addition, genetics studies have revealed that the gene for a cell adhesion molecule called neurexin 1 is defective in some individuals with autism. The research team has discovered that neurexin 1 interacts with nicotinic receptors and direct them to their correct location in brain cells. This preclinical study will ascertain whether neurexins can also modulate the functions of nicotinic receptors. In addition, it aims to determine whether the activation of nicotinic receptors by drugs that bind them will increase neurexin 1 expression in the brain. If this is found to be true, the investigators anticipate that such drugs can be used in clinical trials to correct potential deficiencies in both nicotinic receptors and neurexins in autism spectrum disorders.

Results of this study will help understand the full extent to which dysfunctional regulation of the neurexin/neuroligin family of proteins in autism will disrupt the targeting of different cholinergic nicotinic receptors. This should open the doors to long-term studies to evaluate the potential for using cholinergic agonists to increase maturation of synapses in regions of the brain most relevant to ASD, such as the cerebellum. It is anticipated that such a strategy, if successful in a mouse model, could provide the rationale for targeting cholinergic drugs already in clinical use for the treatment of ASD.