title: Upregulation of calpain correlates with increased neurodegeneration in acute experimental auto-immune encephalomyelitis.
abstract: Although calpain up-regulation is well established in experimental auto-immune encephalomyelitis (EAE), a link between increased calpain expression and activity and neurodegeneration has not been examined. Therefore, spinal cord tissue from Lewis rats with EAE was examined to test the hypothesis that increased calpain expression in neurons would correlate with increased cell death and axonal damage in a time-dependent manner following EAE induction. We found that increased calpain expression in EAE corresponded to increased TUNEL-positive neurons and to increased expression of dephosphorylated neurofilament protein, markers of cell death and axonal degeneration, respectively. An increase in internucleosomal DNA fragmentation in EAE spinal cord suggested that cell death was, at least partially, due to apoptosis. Axonal damage was further demonstrated in EAE spinal cord compared with control via morphological analysis, revealing granular degeneration of filament and microtubule integrity, loss of myelin, and mitochondrial damage. Calcium (Ca2+) influx, which is required for calpain activation, was also increased in EAE spinal cord. From these findings, we conclude that increases in Ca2+-induced calpain activity may play a crucial role in neurodegeneration in acute EAE.
authors.affiliation: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: M Kelly
authors.initials: MK
authors.lastname: Guyton
authors.forename: J Michael
authors.initials: JM
authors.lastname: Wingrave
authors.forename: Anil V
authors.initials: AV
authors.lastname: Yallapragada
authors.forename: Gloria G
authors.initials: GG
authors.lastname: Wilford
authors.forename: Eric A
authors.initials: EA
authors.lastname: Sribnick
authors.forename: Denise D
authors.initials: DD
authors.lastname: Matzelle
authors.forename: William R
authors.initials: WR
authors.lastname: Tyor
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D053938:DNA Fragmentation / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D018709:Statistics, Nonparametric; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D002154:Calpain; D002118:Calcium