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Plasma membrane calcium ATPase deficiency causes neuronal pathology in the spinal cord: a potential mechanism for neurodegeneration in multiple sclerosis and spinal cord injury.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2005 Feb; Vol. 19 (2), pp. 298-300. Date of Electronic Publication: 2004 Dec 02. - Publication Year :
- 2005
-
Abstract
- Dysfunction and death of spinal cord neurons are critical determinants of neurological deficits in various pathological conditions, including multiple sclerosis (MS) and spinal cord injury. Yet, the molecular mechanisms underlying neuronal/axonal damage remain undefined. Our previous studies raised the possibility that a decrease in the levels of plasma membrane calcium ATPase isoform 2 (PMCA2), a major pump extruding calcium from neurons, promotes neuronal pathology in the spinal cord during experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and after spinal cord trauma. However, the causal relationship between alterations in PMCA2 levels and neuronal injury was not well established. We now report that inhibition of PMCA activity in purified spinal cord neuronal cultures delays calcium clearance, increases the number of nonphosphorylated neurofilament H (SMI-32) immunoreactive cells, and induces swelling and beading of SMI-32-positive neurites. These changes are followed by activation of caspase-3 and neuronal loss. Importantly, the number of spinal cord motor neurons is significantly decreased in PMCA2-deficient mice and the deafwaddler(2J), a mouse with a functionally null mutation in the PMCA2 gene. Our findings suggest that a reduction in PMCA2 level or activity leading to delays in calcium clearance may cause neuronal damage and loss in the spinal cord.
- Subjects :
- Animals
Calcium metabolism
Calcium-Transporting ATPases antagonists & inhibitors
Cation Transport Proteins antagonists & inhibitors
Cells, Cultured
Embryo, Mammalian cytology
Mice
Mice, Congenic
Mice, Inbred BALB C
Mice, Inbred Strains
Mice, Mutant Strains
Motor Neurons metabolism
Nerve Degeneration
Neurites enzymology
Neurites metabolism
Neurites pathology
Plasma Membrane Calcium-Transporting ATPases
Rats
Synaptic Transmission physiology
Calcium-Transporting ATPases deficiency
Cation Transport Proteins deficiency
Cell Membrane enzymology
Multiple Sclerosis pathology
Neurons enzymology
Neurons pathology
Spinal Cord pathology
Spinal Cord Injuries pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 19
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 15576480
- Full Text :
- https://doi.org/10.1096/fj.04-2549fje