Regulation of activity-dependent neuroprotective protein (ADNP) by the NO-cGMP pathway in the hippocampus during kainic acid-induced seizure.
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 (N(G)-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.
Cosgrave
Anna S
AS
Department of Veterinary Preclinical Science, Veterinary Faculty, University of Liverpool, Brownlow Hill, Liverpool, L69 7ZJ, UK.
McKay
Jennifer S
JS
AstraZeneca, Department of Pathology Safety Assessment, Alderley Park, Macclesfield, SK10 4TG, UK.
Bubb
Vivien
V
School of Biomedical Sciences, Medical School, University of Liverpool, Liverpool L69 3BX, UK.
Morris
Richard
R
Department of Veterinary Preclinical Science, Veterinary Faculty, University of Liverpool, Brownlow Hill, Liverpool, L69 7ZJ, UK.
Quinn
John P
JP
School of Biomedical Sciences, Medical School, University of Liverpool, Liverpool L69 3BX, UK.
Thippeswamy
Thimmasettappa
T
Department of Veterinary Preclinical Science, Veterinary Faculty, University of Liverpool, Brownlow Hill, Liverpool, L69 7ZJ, UK. Electronic address: tswamy@liv.ac.uk.
D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D006152:Cyclic GMP; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester