Calpain Upregulation in Spinal Cords of Mice with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's Disease

Authors

  • SWAPAN K. RAY,

    1. Department of Neurology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Search for more papers by this author
  • GLORIA G. WILFORD,

    1. Department of Neurology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Search for more papers by this author
  • SYED F. ALI,

    1. Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research-FDA, Jefferson, Arkansas 72079, USA
    Search for more papers by this author
  • NAREN L. BANIK

    Corresponding author
    1. Department of Neurology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    • Address for correspondence: Naren L. Banik, Department of Neurology, Medical University of South Carolina, Charleston, SC 29425. Tel.: (843) 792-3946; fax: (843) 792-8626. e-mail: baniknl@musc.edu

    Search for more papers by this author

Abstract

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a heroin analogue, is a neurotoxin that undergoes in vivo oxidation by monoamine oxidase-B (MAO-B) to 1-methyl-4-phenylpyridinium ion (MPP+) which preferentially exerts its toxic effects on the dopaminergic neurons of the substantia nigra in brain. Spinal interneuronal pathways are also likely to be affected in the course of MPP+ neurotoxicity. The primary effect of MPP+ is mediated by irreversible inhibition of mitochondrial complex I, releasing free radicals. MPP+ may also activate N-methyl-d-aspartate (NMDA) receptors, increasing the cytosolic concentration of free Ca2+. Intracellular free radicals indirectly and free Ca2+ directly can activate Ca2+-dependent proteases such as calpain. We investigated involvement of calpain in spinal cord degeneration due to neurotoxin by subjecting male C57BL/6N mice (17 months old) to MPTP administration (12.5 mg/kg for 0.5 h; 25 mg/kg for 0.25 h; and 50 mg/kg for 0.25, 0.5, 1, 2, and 24 h). RT-PCR and Western blot analysis were performed using the thoracic segment of spinal cords from control and MPTP-administered mice. The administration of MPTP caused calpain upregulation at the mRNA and protein levels to various extents, compared to control mice. Calpain activity was measured by 68 kDa neurofilament protein (NFP) degradation, which was increased in MPTP-induced PD mice. These results suggest that calpain may play a role in spinal cord degeneration in mice with MPTP-induced PD.

Ancillary