In:
Annals of the New York Academy of Sciences, Wiley, Vol. 1053, No. 1 ( 2005-08), p. 269-286
Abstract:
A bstract : To reveal whether increased Ca 2+ permeability of glutamate AMPA channels triggered by the transgene for GluR‐B(N) induces decline in motor functions and neurodegeneration in the spinal cord, we evaluated growth, motor coordination, and spinal reflexes in transgenic GluR‐B(N) and wild‐type (wt) mice. To reveal whether the transgenic GluR‐B(N) expression aggravates the course of motoneuron disease in SOD1 mice, we mated heterozygous GluR‐B(N) and SOD1 [C57BL6Ico‐TgN(hSOD1‐G93A)1Gur] mice to generate double‐transgenic progeny. The phenotypic sequelae in mice carrying mutations were evaluated by monitoring growth, motor coordination, and survival. Neuronal degeneration was assessed by morphological and stereological analysis of spinal cord and brain. We found that transgenic expression in mice of GluR‐B(N)‐containing glutamate AMPA receptors with increased Ca 2+ permeability leads to a late‐onset degeneration of neurons in the spinal cord and decline of motor functions. Neuronal death progressed over the entire life span, but manifested clinically in late adulthood, resembling the course of a slow neurodegenerative disorder. Additional transgenic expression of mutated human SOD1 accelerated disease progression, aggravated severity of motor decline, and decreased survival. These observations reveal that moderate, but persistently elevated Ca 2+ influx via glutamate AMPA channels causes degeneration of spinal motoneurons and motor decline over the span of life. These features resemble the course of sporadic amyotrophic lateral sclerosis (ALS) in humans and suggest that modified function of glutamate AMPA channels may be causally linked to pathogenesis of ALS.
Type of Medium:
Online Resource
ISSN:
0077-8923
,
1749-6632
DOI:
10.1111/nyas.2005.1053.issue-1
DOI:
10.1111/j.1749-6632.2005.tb00034.x
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2834079-6
detail.hit.zdb_id:
211003-9
detail.hit.zdb_id:
2071584-5
SSG:
11
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