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- W2077087730 abstract "Primary cultures of cerebellar granule cells, prepared from cerebella of 7-day-old rats and cultured for 4 or 8 days, were used to study the neurodifferentiative effect of a GABAA receptor agonist, 4,5,6,7-tetrahydroisoxazol[5,4-c]pyridin-3-ol (THIP), on the expression of the α6 GABAA receptor subunit. Membranes prepared from these cultures were photolabeled with the imidazobenzodiazepine [3H]Ro15-4513. In THIP-treated cultures at 4 days in vitro (DIV), photolabeled [3H]Ro15-4513 binding in membranes was significantly increased for both the 51 kilodalton, kDa, (α1 subunit) and 56-kDa (α6 subunit) radioactive peaks in sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). In contrast, THIP-treated granule cells at 8 DIV demonstrated a small but significant decrease from control cultures in the photoincorporation of [3H]Ro15-4513 in the 51-kDa peak; however, no significant change in [3H]Ro15-4513 binding was observed for the 56-kDa polypeptide. Immunolabeling of the α6 subunit using silver-enhanced, immuno-gold staining of granule cells showed a significant effect with THIP treatment only at 4 DIV and not at 8 DIV. Examination by light microscopy demonstrated that the major effect of THIP was to increase α6 subunit clustering on granule cell bodies as well as neurites, 15-fold and sixfold, respectively. Using in situ hybridization, a small THIP-induced increase in α6 mRNA was detected at 4 DIV; however, no effect was apparent at 8 DIV. These data suggest that THIP has a trophic effect on α6 subunit expression, and this effect occurs only at an early developmental stage. Moreover, this study presents further evidence for the role of GABAA agonists, and thus the neurotransmitter, GABA, in regulating the expression of GABAA receptor subunits in the developing cerebellum. J. Neurosci. Res. 50:1053–1062, 1997. © 1997 Wiley-Liss, Inc." @default.
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- W2077087730 date "1997-12-15" @default.
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- W2077087730 title "Expression of the GABAA receptor ?6 subunit in cultured cerebellar granule cells is developmentally regulated by activation of GABAA receptors" @default.
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- W2077087730 doi "https://doi.org/10.1002/(sici)1097-4547(19971215)50:6<1053::aid-jnr17>3.0.co;2-5" @default.
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