Differential effects of SNARE-dependent gliotransmission on behavioral phenotypes in a mouse model of Huntington's disease.

Differential effects of SNARE-dependent gliotransmission on behavioral phenotypes in a mouse model of Huntington's disease. Exp Neurol. 2020 May 06;:113358 Authors: King AC, Wood TE, Rodriquez E, Parpura V, Gray M Abstract Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the widely expressed huntingtin protein. Multiple studies have indicated the importance of mutant huntingtin (mHTT) in astrocytes to HD pathogenesis. Astrocytes exhibit SNARE-dependent exocytosis and gliotransmission, which can be hampered by transgenic expression of dominant negative SNARE (dnSNARE) in these glial cells. We used BACHD mice and crossed them with the dnSNARE model to determine if pan-astrocytic SNARE-dependent exocytosis plays an important role in vivo in the progression of HD behavioral phenotypes. We assessed motor and neuropsychiatric behaviors in these mice. At 12 months of age there was a significant improvement in motor coordination (rotarod test) in BACHD/dnSNARE mice when compared to BACHD mice. Analyses of open field performance revealed significant worsening of center entry (at 9 and 12 months), but not distance traveled in BACHD/dnSNARE when compared to BACHD mice, and variable/inconclusive results on vertical plane entry. While no differences between BACHD and BACHD/dnSNARE mice at 12 months of age in the forced swim test were found, we did observe a significant decr...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research