Up-regulation of the peripheral-type benzodiazepine receptor expression and [(3)H]PK11195 binding in gerbil hippocampus after transient forebrain ischemia.
In mammalian CNS, the peripheral-type benzodiazepine receptor (PTBR) is localized on the outer mitochondrial membrane within the astrocytes and microglia. The main function of PTBR is to transport cholesterol across the mitochondrial membrane to the site of neurosteroid biosynthesis. The present study evaluated the changes in the PTBR density, gene expression and immunoreactivity in gerbil hippocampus as a function of reperfusion time after transient forebrain ischemia. Between 3 to 7 days of reperfusion, there was a significant increase in the maximal binding site density (B(max)) of the PTBR antagonist [(3)H]PK11195 (by 94-156%; P < 0.01) and PTBR mRNA levels (by 1.8- to 2.9-fold; P < 0.01). At 7 days of reperfusion, in the hippocampal CA1 (the brain region manifesting selective neuronal death), PTBR immunoreactivity increased significantly. Increased PTBR expression after transient forebrain ischemia may lead to increased neurosteroid biosynthesis, and thus may play a role in the ischemic pathophysiology.
Rao
V L
VL
Department of Neurological Surgery, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI 53792, USA. Vemugant@neurosurg.wisc.edu
Bowen
K K
KK
Rao
A M
AM
Dempsey
R J
RJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000493:pharmacokinetics*; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013256:Steroids / Q000096:biosynthesis; D014316:Tritium / Q000493:pharmacokinetics; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D000970:Antineoplastic Agents; D007546:Isoquinolines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011993:Recombinant Fusion Proteins; D013256:Steroids; D014316:Tritium; C037850:PK 11195