Generalization of rapidly recurring seizures is suppressed in mice lacking glial cell line-derived neurotrophic factor family receptor alpha2.
Recent experimental evidence indicates that neurotrophic factors play a role in the pathophysiology of epilepsy. The objective of this study was to explore whether signaling through one of the glial cell line-derived neurotrophic factor family receptors, GFRalpha2, influences the severity of kindling-evoked, rapidly recurring seizures and the subsequent development of permanent hyperexcitability. We applied the rapid kindling model to adult mice, using 40 threshold stimulations delivered with 5-min interval in the ventral hippocampus. Generalized seizures were fewer and developed later in response to kindling stimulations in mice lacking GFRalpha2. However, GFRalpha2 gene deletion did not influence the acquisition of the permanent abnormal excitability as assessed 4 weeks later. In situ hybridization revealed marked and dynamic changes of GFRalpha2 mRNA levels in several forebrain areas following the stimulus-evoked seizures. Our findings provide evidence that signaling through the GFRalpha2 receptor contributes to seizure generalization in rapid kindling.
Nanobashvili
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A
Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A-11, University Hospital, SE-221 84 Lund, Sweden. avto.nanobashvili@neurol.lu.se
Kokaia
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Z
Lindvall
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O
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D007696:Kindling, Neurologic / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics
C495040:Gdnf protein, mouse; C494991:Gfra2 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases