Expression of Ret receptor tyrosine kinase after transient forebrain ischemia is modulated by glial cell line-derived neurotrophic factor in rat hippocampus.
The Ret receptor tyrosine kinase is part of a functional receptor complex for the glial cell line-derived neurotrophic factor (GDNF) family. We examined the expression of Ret mRNA after transient forebrain ischemia, and explored the effect of local GDNF-pretreatment in rat hippocampus on Ret mRNA expression. Transient forebrain ischemia induced Ret mRNA expression in the hippocampus, with a peak effect at 12 h. Whereas intrahippocampal microinjection of GDNF (1.0 microg) in sham-operated rats induced the expression of Ret mRNA (peak at 6 to 12 h), the expected increase of Ret mRNA induced by ischemia was blunted by local GDNF-pretreatment. Immunohistochemical investigation revealed that ischemia-induced Ret receptor expression in the hippocampal CA1 region was also reduced by local GDNF-pretreatment. These findings suggest that GDNF modulates the expression of Ret, and that GDNF signaling pathways that involve the Ret receptor tyrosine kinase might play an important role in brain injury induced by ischemia.
Miyazaki
Hiroyuki
H
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, 060-0812, Sapporo, Japan.
Nagashima
Kazuo
K
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D029721:Drosophila Proteins; D015870:Gene Expression / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006624:Hippocampus / Q000201:enzymology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D029721:Drosophila Proteins; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C495001:Ret protein, rat