Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

David R. Beers, Bao Kuang Ho, L. Siklós, Maria E. Alexianu, Dennis R. Mosier, A. Habib Mohamed, Yasushi Otsuka, Milena E. Kozovska, Robert E. McAlhany, R. Glenn Smith, Stanley H. Appel

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)499-509
Number of pages11
JournalJournal of Neurochemistry
Volume79
Issue number3
DOIs
Publication statusPublished - 2001

Fingerprint

Parvalbumins
Motor Neurons
Transgenic Mice
Calcium
Calcium-Binding Proteins
Amyotrophic Lateral Sclerosis
Animals
Genetically Modified Animals
Poisons
Transgenes
Amyotrophic lateral sclerosis 1
Immunoglobulins
Transmitters
Homeostasis
Animal Models

Keywords

  • Calcium-binding proteins
  • Motoneurons
  • Super-oxide dismutase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis. / Beers, David R.; Ho, Bao Kuang; Siklós, L.; Alexianu, Maria E.; Mosier, Dennis R.; Habib Mohamed, A.; Otsuka, Yasushi; Kozovska, Milena E.; McAlhany, Robert E.; Glenn Smith, R.; Appel, Stanley H.

In: Journal of Neurochemistry, Vol. 79, No. 3, 2001, p. 499-509.

Research output: Contribution to journalArticle

Beers, David R. ; Ho, Bao Kuang ; Siklós, L. ; Alexianu, Maria E. ; Mosier, Dennis R. ; Habib Mohamed, A. ; Otsuka, Yasushi ; Kozovska, Milena E. ; McAlhany, Robert E. ; Glenn Smith, R. ; Appel, Stanley H. / Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis. In: Journal of Neurochemistry. 2001 ; Vol. 79, No. 3. pp. 499-509.
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