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

eNeuro. 2016 Sep 6;3(4):ENEURO.0088-15.2016. doi: 10.1523/ENEURO.0088-15.2016. eCollection Jul-Aug 2016.


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.

Keywords: PTEN; calpain; hippocampus; interneurons; seizure; spectrin.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Calpain / genetics
  • Calpain / metabolism*
  • Cell Death / physiology
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Kainic Acid
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Neurons / pathology
  • Neuropeptides / metabolism
  • PTEN Phosphohydrolase / metabolism
  • Rats, Sprague-Dawley
  • Seizures / metabolism*
  • Seizures / pathology
  • Species Specificity
  • Spectrin / metabolism


  • Neuropeptides
  • drebrins
  • Spectrin
  • PTEN Phosphohydrolase
  • Pten protein, mouse
  • Pten protein, rat
  • Calpain
  • Capn1 protein, rat
  • Capn1 protein, mouse
  • Capn2 protein, mouse
  • Capn2 protein, rat
  • Kainic Acid