Differential Activation of Calpain-1 and Calpain-2 following Kainate-Induced Seizure Activity in Rats and Mice.

Autor: Seinfeld J; Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California 91766., Baudry N; Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California 91766., Xu X; Department of Basic Medicine, Western University of Health Sciences , Pomona, California 91766., Bi X; Department of Basic Medicine, Western University of Health Sciences , Pomona, California 91766., Baudry M; Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, California 91766.
Jazyk: angličtina
Zdroj: ENeuro [eNeuro] 2016 Sep 06; Vol. 3 (4). Date of Electronic Publication: 2016 Sep 06 (Print Publication: 2016).
DOI: 10.1523/ENEURO.0088-15.2016
Abstrakt: 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.
Databáze: MEDLINE