Altered Gastrointestinal Function in the Neuroligin-3 Mouse Model of Autism
Abstract
Up to 80% of ASD patients exhibit gastrointestinal (GI) problems, but the underlying mechanisms are unknown. Many ASD associated mutations modify synaptic proteins and hence alter synaptic function in the brain. We propose that some of these mutations also alter the enteric nervous system (ENS) to produce bowel disorders. NL3R451C mice express a neuroligin-3 mutation identified in ASD patients and are more responsive to the GABA neurotransmission in the brain. We investigated motility patterns in isolated jejunum and colon of the mouse model and found significant differences in motility between NL3R451C and wildtype jejunum in control solutions, in part due to altered pacemaker activity. Patterns in the colon are identical in control solutions, but NL3R451C colon is more sensitive to blockade of GABAA receptors. Immunohistochemical localization of neuroligin 3 in both regions confirmed that it is found within the myenteric plexus and appears downregulated in the NL3R451C mouse. Surprisingly, immunoreactivity was prominent in presynaptic varicosities (antiserum specificity confirmed by Western blot) suggesting that neuroligin 3 may act presynaptically. The data provide strong evidence that gastrointestinal dysfunction in autism is related to mechanisms within the enteric nervous system and the intrinsic regulation of gut muscle.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA591042
Entities
People
- Joel C. Bornstein
Organizations
- University of Melbourne