Accession Number : ADA591042


Title :   Altered Gastrointestinal Function in the Neuroligin-3 Mouse Model of Autism


Descriptive Note : Annual rept. 30 Sep 2012-29 Sep 2013


Corporate Author : MELBOURNE UNIV PARKVILLE (AUSTRALIA)


Personal Author(s) : Bornstein, Joel


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a591042.pdf


Report Date : Oct 2013


Pagination or Media Count : 66


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.


Descriptors :   *COLON , *GASTROINTESTINAL SYSTEM , *SMALL INTESTINE , AUSTRALIA , CONTROL , FUNCTIONS , IMMUNE SERUMS , JEJUNUM , MUSCLES , MUTATIONS , NERVOUS SYSTEM , PATIENTS , PATTERNS , PROTEINS , SYNAPSE


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE