Change in neurotrophins and their receptor mRNAs in the rat forebrain after status epilepticus induced by pilocarpine.
We studied the effects of status epilepticus (SE) induced by lithium chloride/pilocarpine treatment on gene expression of neurotrophins of the nerve growth factor (NGF) family and of their high-affinity receptors of the tyrosine protein kinase (trk) family in the forebrain. Using in situ hybridization (ISH), we demonstrated an early (3 h after treatment) increase in brain-derived neurotrophic factor (BDNF) and trkB mRNA expression in the dentate gyrus, amygdala, and piriform cortex, as well as widespread increases in the cerebral cortex. NGF mRNA, but not the mRNA of its receptor trkA, was increased in the dentate gyrus. In contrast, 12 h after treatment, neurotrophin-3 (NT-3) decreased, and its receptor trkC mRNA increased. There was no change in NT-4 mRNA levels. All changes were blocked by pretreatment with scopolamine, a muscarinic antagonist. The noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine blocked NGF, BDNF, and trkB mRNA increases in the hippocampus and cerebral cortex, but not in the amygdala and piriform cortex. In contrast, ketamine did not affect NT-3 and trkC changes. These results provide a complete description of changes in mRNA levels of neurotrophins and their receptors in the forebrain after SE and supply additional data supporting the view that neurotrophin gene expression is related to abnormal neuronal activity.
Mudò
G
G
Institute of Human Physiology, University of Catania, Italy.
Jiang
X H
XH
Timmusk
T
T
Bindoni
M
M
Belluardo
N
N
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects; D015870:Gene Expression; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects; D017403:In Situ Hybridization; D007649:Ketamine / Q000494:pharmacology; D018021:Lithium Chloride; D008297:Male; D009414:Nerve Growth Factors / Q000032:analysis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000235:genetics; D020933:Neurotrophin 3; D010862:Pilocarpine; D016548:Prosencephalon / Q000737:chemistry* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology; D013226:Status Epilepticus / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D012333:RNA, Messenger; D010862:Pilocarpine; D007649:Ketamine; D012601:Scopolamine; D011505:Protein-Tyrosine Kinases; D018021:Lithium Chloride