Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice.
Systemic injection of kainate produces repetitive seizure activity in both rats and mice. It also results in short-term synaptic modifications as well as delayed neurodegeneration. The signaling cascades involved in both short-term and delayed responses are not clearly defined. The calcium-dependent protease calpain is activated in various brain structures following systemic kainate injection, although the precise involvement of the two major brain calpain isoforms, calpain-1 and calpain-2, remains to be defined. It has recently been reported that calpain-1 and calpain-2 play opposite roles in NMDA receptor-mediated neuroprotection or neurodegeneration, with calpain-1 being neuroprotective and calpain-2 being neurodegenerative. In the present study, we determined the activation pattern of calpain-1 and calpain-2 by analyzing changes in levels of different calpain substrates, including spectrin, drebrin, and PTEN (phosphatase and tensin homolog; a specific calpain-2 substrate) in both rats, and wild-type and calpain-1 knock-out mice. The results indicate that, while calpain-2 is rapidly activated in pyramidal cells throughout CA1 and CA3, rapid calpain-1 activation is restricted to parvalbumin-positive and to a lesser extent CCK-positive, but not somatostatin-positive, interneurons. In addition, calpain-1 knock-out mice exhibit increased long-term neurodegeneration in CA1, reinforcing the notion that calpain-1 activation is neuroprotective.
Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California 91766.
Jeff
J
Seinfeld
Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California 91766.
Neema
0000-0002-5142-241X
N
Baudry
Department of Basic Medicine, Western University of Health Sciences , Pomona, California 91766.
Xiaobo
X
Xu
Department of Basic Medicine, Western University of Health Sciences , Pomona, California 91766.
Xiaoning
X
Bi
Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California 91766.
Michel
0000-0002-5142-241X
M
Baudry
D000818:Animals; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism* / Q000473:pathology; D013045:Species Specificity; D013049:Spectrin / Q000378:metabolism
D009479:Neuropeptides; C053386:drebrins; D013049:Spectrin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; C487216:Pten protein, rat; D002154:Calpain; C000606071:Capn1 protein, rat; C112682:Capn1 protein, mouse; C570925:Capn2 protein, mouse; C000594975:Capn2 protein, rat; D007608:Kainic Acid
PTEN; calpain; hippocampus; interneurons; seizure; spectrin