Fig. 2.

Molecular analyses of tgHD P10 striata. (A) Microarray analysis of rat striata at P10 (WT vs. HOM, n = 5 each) demonstrated clusters of up- (yellow) and down- (blue) regulated gene expression. (B) Ingenuity Pathway Analysis revealed 17 target mRNAs associated with behavior, 7 of which (#) were validated by qRT-PCR (P values are from ANOVA vs. WT; n > 8). (C) Network analysis indicated deregulation of dopaminergic signaling; relevant pathways are highlighted in yellow). Rat P10 striatal mRNA expression of DARPP-32, PKA, and dopamine receptor D1A is down-regulated, whereas the expression of the dopamine transporter Slc6a3 is up-regulated. (D) Data are displayed as mean normalized expression (percentage of WT; ANOVA; n > 8). (E) DARPP-32 down-regulation two-tailed t test; n > 5) could be confirmed in Western blot studies. Phosphorylation levels of DARPP-32 (Thr³⁴ and Thr⁷⁵) in P10 striata were not significantly different in WT and transgenic pups. (F) Receptor autoradiography revealed a significant reduction of dopamine receptor D1A density and NMDAR density in the striata of transgenic rat pups (two-tailed t test; n = 5). Representative autoradiographs of coronal sections of P10 rats are presented. (G) Immunohistochemistry confirmed the reduced expression of DARPP32 and TH in the striatum of P10 tgHD pups (shown are representative images from n = 10 pups). Data represent means ± SEM: *P < 0.05, **P < 0.01, and ***P < 0.001 vs. WT pups.