1. Calpastatin Overexpression Protects against Excitotoxic Hippocampal Injury and Traumatic Spinal Cord Injury
- Author
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Kathryn E. Saatman, Dexter V. Reneer, Glenn C. Telling, James W. Geddes, Chen Guang Yu, Aashish Joshi, and Vimala Bondada
- Subjects
030506 rehabilitation ,Proteases ,Traumatic spinal cord injury ,Excitotoxicity ,Mice, Transgenic ,Hippocampal formation ,medicine.disease_cause ,Hippocampus ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Humans ,Medicine ,Spinal cord injury ,Spinal Cord Injuries ,Calpastatin ,biology ,business.industry ,Calcium-Binding Proteins ,Neurodegeneration ,Calpain ,Original Articles ,medicine.disease ,biology.protein ,Neurology (clinical) ,0305 other medical science ,business ,Neuroscience ,Locomotion ,030217 neurology & neurosurgery - Abstract
Small molecule inhibitors of calcium-dependent proteases, calpains (CAPNs), protect against neurodegeneration induced by a variety of insults including excitotoxicity and spinal cord injury (SCI). Many of these compounds, however, also inhibit other proteases, which has made it difficult to evaluate the contribution of calpains to neurodegeneration. Calpastatin is a highly specific endogenous inhibitor of classical calpains, including CAPN1 and CAPN2. In the present study, we utilized transgenic mice that overexpress human calpastatin under the prion promoter (PrP-hCAST) to evaluate the hypothesis that calpastatin overexpression protects against excitotoxic hippocampal injury and contusive SCI. The PrP-hCAST organotypic hippocampal slice cultures showed reduced neuronal death and reduced calpain-dependent proteolysis (α-spectrin breakdown production, 145 kDa) at 24 h after N-methyl-D-aspartate (NMDA) injury compared with the wild-type (WT) cultures (n = 5, p
- Published
- 2020