Nitric oxide regulates activity-dependent neuroprotective protein (ADNP) in the dentate gyrus of the rodent model of kainic acid-induced seizure.
The dentate gyrus (DG) of the normal rat brain contains activity-dependent neuroprotective protein (ADNP) which is widely distributed in the cytoplasm of neurons and astrocytes. Treatment with nitric oxide (NO) synthase (NOS) inhibitor N(G)-nitro-L: -arginine methyl ester (L: -NAME) caused a decrease in ADNP expression in granule cells which persisted 3 days post-treatment. However, treatment with neuronal-specific NOS inhibitor, 7-nitroindazole (7-NI), or soluble guanylyl cyclase inhibitor, ODQ, did not change ADNP expression in the DG. We have previously shown that kainic acid (KA)-induced seizure increases neuronal NOS in neurons and inducible NOS in glia cells and suppresses ADNP in the hippocampus (Cosgrave et al., Neurobiol Dis 30(3):281-292, 2008). In the DG, L: -NAME treatment prior to KA causes ADNP synthesis in granule cells by 3 h which was later restricted to the subgranular zone by 3 days. 7-NI and ODQ had no effect. Double immunostaining for neuronal marker NeuN and ADNP revealed a significant decrease of both ADNP(+) neurons and of total neuron numbers (NeuN(+)) in the hilus of animals having KA-induced seizure that had been pretreated with L: -NAME implying that NO and ADNP may act together to protect hilar neurons. Overall, these observations suggest that NO regulates ADNP in the DG under both basal and pathophysiological conditions.
Cosgrave
Anna S
AS
Department of Veterinary Preclinical Sciences, Veterinary Faculty, University of Liverpool, Brownlow Hill, Liverpool, L69 7ZJ, UK.
McKay
Jennifer S
JS
Morris
Richard
R
Quinn
John P
JP
Thippeswamy
Thimmasettappa
T
D000818:Animals; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced*; D000071756:Soluble Guanylyl Cyclase
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester