Accession Number : AD1028496


Title :   Disruption of Trophic Inhibitory Signaling in Autism Sepctrum Disorders


Descriptive Note : Technical Report,30 Sep 2014,29 Sep 2016


Corporate Author : Northwestern University Evanston United States


Personal Author(s) : Contractor,Anis


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1028496.pdf


Report Date : 01 Dec 2016


Pagination or Media Count : 11


Abstract : We have examined alterations in inhibitory GABA signaling in mouse models of ASDs as well as in human iPS derived neurons. We had previously demonstrated that the maturation of the reversal potential for GABA (EGABA) is delayed in the Fragile X mouse model. In this project we proposed to determine whether this alteration in the maturation of EGABA was a convergent alterations in ASDs with multiple genetic origins, which would make it an important target pathway in ASDs. Also we proposed to determine whether inhibiting one of the chloride co-transporters that control EGABA could be used as a corrective strategy for the synaptic and circuit disruptions demonstrated in the Fragile X mouse model. We found: 1) that EGABA development was not disrupted in the mouse model of Angelman Syndrome 2) EGABA development was delayed in human induced neurons derived from Fragile X patient fibroblasts 3) Inhibiting the Cl- co-transporters that regulate EGABA by administration of bumetanide to mice rescues synaptic and circuit dysfunction in Fragile X mice.


Descriptors :   AUTISM , SYNAPSES , neurosciences , NEURONS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE