Endogenous opioids inhibit ischemia-induced generation of immature hippocampal neurons via the mu-opioid receptor.
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 mu-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.
Kolodziej
Angela
A
Institute of Pharmacology and Toxicology, Otto-von-Guericke-University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Stumm
Ralf
R
Becker
Axel
A
Höllt
Volker
V
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D018847:Opioid Peptides / Q000235:genetics / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D018847:Opioid Peptides; D017450:Receptors, Opioid, mu