Altered gene expression for calpain/calpastatin system in motor neuron degeneration ( Mnd) mutant mouse brain and spinal cord

• Published in: Brain research. Molecular brain research. 1998, Vol.53 (1), p.174-186
• Main Authors: Li, Jinhe, Nixon, Ralph, Messer, Anne, Berman, Stephen, Bursztajn, Sherry
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - metabolism; Calcium-Binding Proteins - biosynthesis; Calpain; Calpain - biosynthesis; Calpastatin; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Primers; Female; Gene Expression Regulation; Hippocampus; In Situ Hybridization; Male; Medical sciences; Mice; Mice, Mutant Strains; Mnd mice; Motor Neurons - metabolism; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; Neuroglia - metabolism; Neurology; Neurons - metabolism; Organ Specificity; Polymerase Chain Reaction; Purkinje Cells - metabolism; Spinal cord; Spinal Cord - metabolism
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(97)00295-7

The calcium-activated neutral proteases (CANP, calpains) have been implicated in both acute and chronic neurodegenerative processes. In the present study, we analyzed the in situ mRNA expression of calpain I and II and their endogenous inhibitor, calpastatin, in the motor neuron degeneration ( mnd) mutant mouse, which exhibits progressive dysfunction of the spinal cord and brain. As the disease progresses, the mutants show increasingly pronounced motor abnormalities which coincide with swelling of the spinal motor neurons, neocortex, hippocampal CA regions and cerebellar Purkinje cells. In situ hybridization studies show that the mnd/mnd mice have a significantly higher level of calpain I, calpain II and calpastatin than the congenic controls in the following brain regions and cell types: hippocampal CA3 region, pyramidal cells, cerebellar Purkinje cells and spinal cord motor neurons. However, no differences in calpain or calpastatin mRNA levels are observed in glial and cerebellar granule cells of mnd/mnd (m/m) and control mice. Western blots and competitive RT-PCR analyses of brain and spinal cord homogenates are confirmative. Such altered gene expression in specific cell types of brain and spinal cord suggests the involvement of the calpain/calpastatin system.