title: Lack of sigma-1 receptor exacerbates ALS progression in mice.
abstract: The function of the sigma-1 receptor (S1R) has been implicated in modulating the activity of various ion channels. In the CNS S1R is enriched in cholinergic postsynaptic densities in spinal cord motoneurons (MNs). Mutations in S1R have been found in familial cases of amyotrophic lateral sclerosis (ALS). In this study we show that a knockout of S1R in the SOD1*G93A mouse model of ALS significantly reduces longevity (end stage). Electrophysiological experiments demonstrate that MN of mice lacking S1R exhibit increased excitability. Taken together the data suggest the S1R acts as a brake on excitability, an effect that might enhance longevity in an ALS mouse model.
authors: Department of Neuroscience, University of Wisconsin, School of Medicine and Public Health, 1300 University Avenue, Madison, WI 53706, USA. tamavlyutov@wisc.edu
authors: T A
authors: TA
authors: Mavlyutov
authors: M L
authors: ML
authors: Epstein
authors: Y I
authors: YI
authors: Verbny
authors: M S
authors: MS
authors: Huerta
authors: I
authors: I
authors: Zaitoun
authors: L
authors: L
authors: Ziskind-Conhaim
authors: A E
authors: AE
authors: Ruoho
mesh_terms: D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D004195:Disease Models, Animal; D018450:Disease Progression; D004558:Electric Stimulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D066298:In Vitro Techniques; D008136:Longevity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D017480:Receptors, sigma / Q000172:deficiency* / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D013550:Swimming / Q000523:psychology; D014157:Transcription Factors / Q000235:genetics; D000097605:Sigma-1 Receptor
chemical_list: D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D017480:Receptors, sigma; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000097605:Sigma-1 Receptor; C485184:enhanced green fluorescent protein; C084059:Hb9 protein, mouse; C109415:SOD1 G93A protein