title: 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.
abstract: 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.
authors.affiliation: Department of Veterinary Preclinical Sciences, University of Liverpool, Brownlow Hill, Liverpool, UK.
authors.forename: Anna Siobhan
authors.initials: AS
authors.lastname: Cosgrave
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: McKay
authors.forename: Thimmasettappa
authors.initials: T
authors.lastname: Thippeswamy
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000071756:Soluble Guanylyl Cyclase; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D007191:Indazoles; D010069:Oxadiazoles; D011810:Quinoxalines; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D007608:Kainic Acid; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester