Immunofluorescent labeling of increased calpain expression and neuronal death in the spinal cord of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.
Parkinson's disease (PD) is a movement disorder characterized by rigidity, tremor, and bradykinesia, originating from degeneration of dopaminergic neurons in the substantia nigra (SN), retrorubral area, and locus ceoruleus (LC). Calpain has been implicated in the pathophysiology of neurodegenerative diseases. Since the spinal cord (SC) and brain are integrally connected and calpain is involved in cell death and mitochondrial dysfunction, we hypothesized that SC neurons are also affected in PD. In order to examine this hypothesis, we examined both brain and SC from mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To identify cells expressing calpain, double immunofluorescent labeling was performed with antibodies specific for calpain and a cell type (OX-42, GFAP, or NeuN). Combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labeling were used to identify death of specific cells in the central nervous system (CNS). There was an increase in calpain expression in microglia, astrocytes, and neurons in the SC of MPTP-treated mice at 1 and 7 days, as compared to controls. TUNEL-positive neurons in the SC and SN showed apoptotic characteristics. These results demonstrated that neuronal death occurred not only in SN but also in the SC of MPTP-treated mice and has provided evidence for a possible calpain-mediated SC neuronal death in MPTP-induced parkinsonism in mice.
Chera
Bhisham
B
Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street, PO Box 250606, Charleston, SC 29425, USA.
Schaecher
Kurt E
KE
Rocchini
Anne
A
Imam
Syed Z
SZ
Sribnick
Eric A
EA
Ray
Swapan K
SK
Ali
Syed F
SF
Banik
Naren L
NL
D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D002154:Calpain / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C497887:Bsg protein, mouse; C079432:Bsg protein, rat; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D051926:Basigin; D002154:Calpain