title: Astrocytes show reduced support of motor neurons with aging that is accelerated in a rodent model of ALS.
abstract: Astrocytes play a crucial role in supporting motor neurons in health and disease. However, there have been few attempts to understand how aging may influence this effect. Here, we report that rat astrocytes show an age-dependent senescence phenotype and a significant reduction in their ability to support motor neurons. In a rodent model of familial amyotrophic lateral sclerosis (ALS) overexpressing mutant superoxide dismutase 1 (SOD1), the rate of astrocytes acquiring a senescent phenotype is accelerated and they subsequently provide less support to motor neurons. This can be partially reversed by glial cell line-derived neurotrophic factor (GDNF). Replacing aging astrocytes with young ones producing GDNF may therefore have a significant survival promoting affect on aging motor neurons and those lost through diseases such as ALS.
authors.affiliation: Cedars-Sinai Medical Center, The Regenerative Medicine Institute, Los Angeles, CA, USA.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: Das
authors.affiliation: Cedars-Sinai Medical Center, The Regenerative Medicine Institute, Los Angeles, CA, USA. Electronic address: clive.svendsen@cshs.org.
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
mesh_terms: D000375:Aging / Q000473:pathology*; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D001253:Astrocytes / Q000473:pathology* / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D009046:Motor Neurons / Q000473:pathology*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D015850:Interleukin-6; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Aging; Amyotrophic lateral sclerosis; Astrocytes; Cellular senescence; Glial cell line-derived neurotrophic factor; Interleukin-6; Superoxide dismutase 1