Involvement of the calcium-independent receptor for alpha-latrotoxin in brain ischemia.
Cerebral ischemia is caused by a reduced blood supply to neurons, and vulnerability to neurodegeneration varies considerably among neuronal types. In hippocampus, neurons in the CA1 region are more susceptible to ischemia-induced neuronal death than neurons in the CA3 region, and in response to transient forebrain ischemia a family of calcium-dependent receptors for alpha-latrotoxin is differentially expressed in the two regions. Here, we report that an ischemic insult up-regulated a family of calcium-independent receptors for alpha-latrotoxin (CIRL) mRNAs in CA1 neurons and down-regulated their mRNAs in CA3 neurons. Furthermore, antisense oligonucleotides complementary to CIRL-1 mRNA or CIRL-3 mRNA suppressed neuronal death associated with hypoxia in hippocampal and cortical cell cultures. The observed region-specific CIRL mRNA expression in hippocampus and an in vitro rescue experiment by antisense oligonucleotides against CIRL mRNAs suggest a functional importance of CIRL in neurodegeneration.
Bin Sun
Hui
H
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA.
Ruan
Yiwen
Y
Xu
Zao C
ZC
Yokota
Hiroki
H
D000818:Animals; D016923:Cell Death / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
C467733:ADGRL1 protein, human; C513284:ADGRL3 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide