Regulation of activity-dependent neuroprotective protein (ADNP) by the NO-cGMP pathway in the hippocampus during kainic acid-induced seizure

• Main Authors: Anna S. Cosgrave, Jennifer S. McKay, Vivien Bubb, Richard Morris, John P. Quinn, Thimmasettappa Thippeswamy
• Format: Article
• Language: English
• Published: Elsevier 2008-06-01
• Series: Neurobiology of Disease
• Subjects: Epilepsy; Kainic acid; Neuroprotection; ADNP; Nitric oxide synthase blockers; cGMP
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996108000211

Activity-dependent neuroprotective protein (ADNP) is widely distributed in the cytoplasm of neurons and astrocytes of the hippocampus. Kainic acid (KA)-induced seizures increases neuronal nitric oxide synthase (nNOS) in neurons and inducible NOS (iNOS) in glia cells which coincides with a reduction in ADNP in the hippocampus. Inhibitors of NOS or soluble guanylyl cyclase (sGC) activity reduce ADNP under basal conditions in the absence of seizures. Treating animals with these inhibitors prior to KA-induced seizure, in particular, L-NAME (NG-nitro-l-arginine methyl ester), advances the onset of the first seizure but reverses the loss of ADNP by 3 days after the first seizure. This suggests that the NO-cGMP pathway has a role in regulating ADNP under both basal physiological conditions and in the pathophysiological changes produced during epileptogenesis.