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Expression of mutant SOD1 G93A in astrocytes induces functional deficits in motoneuron mitochondria
Author(s) -
Bilsland Lynsey G.,
Nirmalananthan Niranjanan,
Yip Jing,
Greensmith Linda,
Duchen Michael R.
Publication year - 2008
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 - 10.1111/j.1471-4159.2008.05699.x
Subject(s) - sod1 , mitochondrion , biology , astrocyte , amyotrophic lateral sclerosis , motor neuron , microbiology and biotechnology , neuroglia , neuroscience , superoxide dismutase , oxidative stress , central nervous system , pathology , medicine , endocrinology , spinal cord , disease
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneuron degeneration resulting in paralysis and eventual death. ALS is regarded as a motoneuron‐specific disorder but increasing evidence indicates non‐neuronal cells play a significant role in disease pathogenesis. Although the precise aetiology of ALS remains unclear, mutations in the superoxide dismutase (SOD1) gene are known to account for approximately 20% of familial ALS. We examined the influence of SOD1 G93A expression in astrocytes on mitochondrial homeostasis in motoneurons in a primary astrocyte : motoneuron co‐culture model. SOD1 G93A expression in astrocytes induced changes in mitochondrial function of both SOD1 G93A and wild‐type motoneurons. In the presence of SOD1 G93A astrocytes, mitochondrial redox state of both wild‐type and SOD1 G93A motoneurons was more reduced and mitochondrial membrane potential decreased. While intra‐mitochondrial calcium levels [Ca 2+ ] m were elevated in SOD1 G93A motoneurons, changes in mitochondrial function did not correlate with [Ca 2+ ] m . Thus, expression of SOD1 G93A in astrocytes directly alters mitochondrial function even in embryonic motoneurons, irrespective of genotype. These early deficits in mitochondrial function induced by surrounding astrocytes may increase the vulnerability of motoneurons to other neurotoxic mechanisms involved in ALS pathogenesis.