Differential Regulation of Vasoactive Intestinal Peptide (VIP) in the Dentate Gyrus and Hippocampus via the NO-cGMP Pathway Following Kainic Acid-Induced Seizure in the Rat

作者：Cosgrave Anna Siobhan; McKay Jennifer S; Thippeswamy Thimmasettappa^*

来源：Journal of Molecular Neuroscience, 2010, 42(3): 359-369.

DOI：10.1007/s12031-010-9353-x

• Nitric oxide
• VIP
• cGMP
• Epilepsy
• Kainic acid

We have previously shown that kainic acid (KA) increases nitric oxide (NO) synthase (NOS) production in the rat dentate gyrus (DG) and hippocampus (CA3), and NOS inhibition [(by N(G)-nitro-L-arginine methylester (L-NAME)] modulates the vasoactive intestinal peptide (VIP)-responsive gene, activity-dependent neuroprotective protein, and alters neuro- and astrogliogenesis (Cosgrave et al. in Neurobiol Dis 30(3):281-292 2008, J Mol Neurosci 39(1-2):9-21, 2009, 2010). In the present study, using the same model we demonstrate that VIP synthesis is differentially regulated by the NO-cyclic guanosine monophosphate (cGMP) pathway in the DG and CA3 at 3 h and 3 days post-KA. At 3 h post-KA: In L-NAME+KA/7-nitroindazole (7-NI)+KA, stratum granulosum (SG) and subgranular zone (SGZ) cells were intensely stained for VIP when compared with L-NAME/7-NI/KA alone. Soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, blocks cGMP production), suppressed astrocytic activation (glial fibrillary acidic protein) but other cell types were VIP(+); however, ODQ+KA suppressed overall VIP synthesis in the DG. At 3 days post-KA: In L-NAME+KA/7-NI+KA, SGZ and SG cells continued to express VIP, while in the KA alone, only SGZ cells were VIP(+). ODQ increased VIP(+) cells in the SG, and in contrast to 3 h, VIP-containing nNOS(+) cells increased in ODQ+KA when compared to vehicle+KA. In the hippocampus, 7-NI/ODQ had no effect on VIP at 3 h/3 days, while L-NAME+KA at 3 days increased VIP(+) cells, but reduced VIP-like immunoreactivity in astrocytes. These results suggest that the NO-cGMP pathway differentially regulates VIP in the DG and hippocampus during seizure.

• 出版日期2010-11