Expression of the mu-opioid receptor is induced in dentate gyrus granule cells after focal cerebrocortical ischaemia and stimulation of entorhinal afferents.
Focal ischaemia in the cerebral cortex affects the inducibility of long-term potentiation (LTP) in the hippocampus. This impairment of hippocampal function may result from excessive activation of cortico-hippocampal afferents and subsequent perturbation of hippocampal LTP-relevant transmitter systems, which include opioids. Here, we tested if permanent focal ischaemia and electrical afferent stimulation influence the expression of the mu-opioid receptor (MOR) in the rat hippocampus. In the applied ischaemia model, the entire ipsilateral cortical hemisphere and hippocampus experienced sustained excitation as indicated by a long-lasting increase in the expression of arg 3.1/arc (ARG) mRNA, a marker for neuronal activity. Expression of MOR mRNA and protein was strongly increased in granule cells, which contain very low MOR levels under normal conditions, but not in gamma-aminobutyric acid (GABA)ergic neurons, which express the MOR constitutively. In the molecular layer, which contains the dendrites of granule cells, focal ischaemia caused a redistribution of MOR-like immunoreactivity. In contrast to the dentate gyrus, MOR expression was unaltered in the hippocampus proper and in non-infarcted cortical areas. Repetitive high-frequency stimulation of cortico-hippocampal perforant path afferents induced strong MOR mRNA expression throughout the granular layer. However, weak tetanization sufficient to induce LTP and ARG expression did not influence MOR mRNA levels. Taken together, we provide direct evidence for the induction of MOR expression in granule cells experiencing sustained excitation by cortical afferents. In activated, MOR-expressing granule cells, inhibitory opioids may counter-regulate glutamatergic excitation by the perforant path.
Stumm
Ralf
R
Department of Pharmacology and Toxicology, Otto-von-Guericke University, 39120 Magdeburg, Germany. ralf.stumm@medizin.uni-magdeburg
Rüthrich
Heinz
H
Schulz
Stefan
S
Zhou
Chun
C
Hollt
Volker
V
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018728:Entorhinal Cortex / Q000503:physiopathology / Q000528:radiation effects*; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology* / Q000528:radiation effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D017774:Long-Term Potentiation / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000528:radiation effects; D019580:Perforant Pathway / Q000502:physiology* / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; C092069:activity regulated cytoskeletal-associated protein; D005968:Glutamate Decarboxylase