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Valproate Enhances Neuropeptide Y Expression: Modulating the Modulators
Author(s) -
Lagrange Andre H.
Publication year - 2007
Publication title -
epilepsy currents
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.415
H-Index - 22
eISSN - 1535-7511
pISSN - 1535-7597
DOI - 10.1111/j.1535-7511.2007.00167.x
Subject(s) - neuropeptide y receptor , endocrinology , medicine , somatostatin , neuropeptide , receptor , anticonvulsant , antagonist , epilepsy , psychiatry
Brill J, Lee M, Zhao S, Fernald RD, Huguenard JR. J Neurosci 2006;26:6813–6822. Valproate (VPA) can suppress absence and other seizures, but its precise mechanisms of action are not completely understood. We investigated whether VPA influences the expression of neuropeptide Y (NPY), an endogenous anticonvulsant. Chronic VPA administration to young rats (300–600 mg · kg −1 · d −1 in divided doses over 4 d) resulted in a 30–50% increase in NPY mRNA and protein expression in the nucleus reticularis thalami (nRt) and hippocampus, but not in the neocortex, as shown by real‐time PCR, radioimmunoassay, and immunohistochemistry. No increased expression was observed after a single acute dose of VPA. Chronic treatment with the pharmacologically inactive VPA analog octanoic acid did not elicit changes in NPY expression. No significant expression changes could be shown for the mRNAs of the Y 1 receptor or of the neuropeptides somatostatin, vasoactive intestinal polypeptide, and choleocystokinin. Fewer synchronous spontaneous epileptiform oscillations were recorded in thalamic slices from VPA‐treated animals, and oscillation duration as well as the period of spontaneous and evoked oscillations were decreased. Application of the Y 1 receptor inhibitor N 2‐(diphenylacetyl) ‐N‐ [(4‐hydroxyphenyl)methyl]‐ d ‐arginine‐amide (BIBP3226) enhanced thalamic oscillations, indicating that NPY is released during those oscillations and acts to downregulate oscillatory strength. Chronic VPA treatment significantly potentiated the effect of BIBP3226 on oscillation duration but not on oscillation period. These results demonstrate a novel mechanism for the antiepileptic actions of chronic VPA therapy.

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