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Parvalbumin overexpression alters immune‐mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis
Author(s) -
Beers David R.,
Ho BaoKuang,
Siklós Laszlo,
Alexianu Maria E.,
Mosier Dennis R.,
Mohamed A. Habib,
Otsuka Yasushi,
Kozovska Milena E.,
McAlhany Robert E.,
Smith R. Glenn,
Appel Stanley H.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00582.x
Subject(s) - parvalbumin , amyotrophic lateral sclerosis , genetically modified mouse , transgene , calcium , calcium in biology , biology , calcium binding protein , sod1 , intracellular , neuroscience , endocrinology , microbiology and biotechnology , medicine , biochemistry , disease , gene
Intracellular calcium is increased in vulnerable spinal motoneurons in immune‐mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium‐binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune‐mediated increases in calcium and to a lesser extent compensate for the mSOD1‐mediated ‘toxic‐gain‐of‐function’ in transgenic mice.