Fig. 5.

Alterations in amygdala genomic profile resulting from prenatal VPA exposure. Pathway changes predicted in animals exposed to VPA prenatally differed across time, with enhancements in developmental and growth pathways predicted early and reductions predicted later in development (a). Predicted reductions (blue) or enhancements (red) common to P21 proteomic and transcriptomic analyses were observed in pathways involved in neurotransmission and synaptic plasticity (b). G-protein coupled receptor activation of Gα12/13 proteins leads to activation of Rho GTPases by dissociating from the inhibitory RhoGDI, and one pathway is through the release of the inhibitory PKA from RhoGEF [110]. Reductions in ROCK2, a downstream effector that inhibits dendritic remodeling, may lead to structural changes in dendritic spines in VPA animals. VPA-exposed animals displayed impaired ephrin receptor and calcium signaling pathways, with reduced Ryr2 and Cacna2d1 expression in both transcriptomic and proteomic analyses. CACNA2D1 voltage-gated calcium channel auxiliary subunit, RYR2 ryanodine receptor 2, PKA protein kinase A, GEF guanine nucleotide exchange factor, GDI guanine nucleotide dissociation inhibitor, ROCK2 Rho kinase 2