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Endogenous opioids inhibit ischemia‐induced generation of immature hippocampal neurons via the µ‐opioid receptor
Author(s) -
Kolodziej Angela,
Stumm Ralf,
Becker Axel,
Höllt Volker
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06111.x
Subject(s) - neurogenesis , neun , knockout mouse , hippocampal formation , neuroscience , endogenous opioid , ischemia , doublecortin , gene knockout , endogeny , granule cell , endocrinology , medicine , biology , receptor , microbiology and biotechnology , dentate gyrus , opioid , biochemistry , immunohistochemistry , gene
It is established that hippocampal neurogenesis is dynamically regulated by physiological and pathological stimuli including learning, environmental complexity, mental disorders and brain lesion. Little is known about factors regulating adaptive changes in neurogenesis. Using µ‐opioid receptor (MOP)‐knockout mice we addressed whether endogenous opioids influence ischemia‐induced enhancement of hippocampal neurogenesis. Permanent middle cerebral artery occlusion (MCAO) produced similar corticostriatal infarcts in MOP‐knockout and wildtype mice. Analyses of BrdU/doublecortin‐colabelled cells in the granule cell layer 14 days after MCAO showed that ischemic knockouts contained more immature neurons generated during days 9–11 than wildtypes. After 29 days, similar quantities of BrdU/NeuN‐labelled cells were found in ischemic knockout and wildtype mice, suggesting that granule cells that were formed in excess during days 9–11 in the knockouts were eliminated by day 29. Neurogenesis was similar in knockout and wildtype mice subjected to sham operation. In addition to a transient increase in neurogenesis, MCAO caused a transient up‐regulation of preprodynorphin and preproenkephalin mRNA expression in the granule cell layer. Our findings suggest that activated signalling via endogenous opioids and the MOP limits the enhanced generation of neuronal cells after ischemic corticostriatal lesions.