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Nitric Oxide Regulates Activity-Dependent Neuroprotective Protein (ADNP) in the Dentate Gyrus of the Rodent Model of Kainic Acid-Induced Seizure

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Abstract

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 NG-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.

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Abbreviations

ADNP:

activity-dependent neuroprotective protein

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

CA:

Cornu Ammonis

cGMP:

cyclic guanosine monophosphate

KA:

kainic acid

l-NAME:

NG-nitro-l-arginine methyl ester

MAPK:

mitogen-activated protein kinase

7-NI:

7-nitroindazole

NMDA:

N-methyl-d-aspartate

ODQ:

1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one

NO:

nitric oxide

nNOS:

neuronal NO synthase

qPCR:

quantitative polymerase chain reaction

sGC:

soluble guanylyl cyclase

SLM:

stratum lacunosum moleculare

SP:

stratum pyramidale

VIP:

vasoactive intestinal peptide

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Acknowledgements

We would like to thank the Faculty of Veterinary Science, University of Liverpool and the Department of Pathology, Safety Assessment, AstraZeneca, Macclesfield, UK for their studentship funding.

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Authors and Affiliations

  1. Department of Veterinary Preclinical Sciences, Veterinary Faculty, University of Liverpool, Brownlow Hill, Liverpool, L69 7ZJ, UK

    Anna S. Cosgrave, Richard Morris & Thimmasettappa Thippeswamy

  2. School of Biomedical Sciences, Medical School, University of Liverpool, Liverpool, L69 3BX, UK

    John P. Quinn

  3. AstraZeneca, Department of Pathology Safety Assessment, Alderley Park, Macclesfield, SK10 4TG, UK

    Jennifer S. McKay

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  1. Anna S. Cosgrave
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Correspondence to Thimmasettappa Thippeswamy.

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Cosgrave, A.S., McKay, J.S., Morris, R. et al. Nitric Oxide Regulates Activity-Dependent Neuroprotective Protein (ADNP) in the Dentate Gyrus of the Rodent Model of Kainic Acid-Induced Seizure. J Mol Neurosci 39, 9–21 (2009). https://doi.org/10.1007/s12031-008-9169-0

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