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Kreilaus, Fabian; Guerra, Stefan; Masanetz, Rebecca; Menne, Victoria; Yerbury, Justin; Karl, Tim

Novel behavioural characteristics of the superoxide dismutase 1 G93A (SOD1G93A) mouse model of amyotrophic lateral sclerosis include sex‐dependent phenotypes

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  • Medientyp: E-Artikel
  • Titel: Novel behavioural characteristics of the superoxide dismutase 1 G93A (SOD1G93A) mouse model of amyotrophic lateral sclerosis include sex‐dependent phenotypes
  • Beteiligte: Kreilaus, Fabian; Guerra, Stefan; Masanetz, Rebecca; Menne, Victoria; Yerbury, Justin; Karl, Tim
  • Erschienen: Wiley, 2020
  • Erschienen in: Genes, Brain and Behavior
  • Sprache: Englisch
  • DOI: 10.1111/gbb.12604
  • ISSN: 1601-1848; 1601-183X
  • Schlagwörter: Behavioral Neuroscience ; Neurology ; Genetics
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) involves the rapid degeneration of upper and lower motor neurons leading to weakening and paralysis of voluntary movements. Mutations in <jats:italic>copper‐zinc superoxide dismutase 1</jats:italic> (<jats:italic>SOD1</jats:italic>) are a known genetic cause of ALS, and the <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> mouse has been used extensively to investigate molecular mechanisms in ALS. In recent years, evidence suggests that ALS and frontotemporal dementia form a spectrum disorder ranging from motor to cognitive dysfunctions. Thus, we tested male and female <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> mice for the first time before the onset of debilitating motor impairments in behavioural domains relevant to both ALS and frontotemporal dementia. <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> males displayed reduced locomotion, exploration and increased anxiety‐like behaviours compared with control males. Intermediate‐term spatial memory was impaired in <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> females, whereas long‐term spatial memory deficits as well as lower acoustic startle response, and prepulse inhibition were identified in <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> mice of both sexes compared with respective controls. Interestingly, <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> males exhibited an increased conditioned cue <jats:italic>freezing</jats:italic> response. <jats:italic>Nosing</jats:italic> behaviours were also elevated in both male and female <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> when assessed in social paradigms. In conclusion, <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> mice exhibit a variety of sex‐specific behavioural deficits beyond motor impairments supporting the notion of an ALS‐frontotemporal spectrum disorder. Thus, <jats:italic>SOD1</jats:italic><jats:sup> <jats:italic>G93A</jats:italic></jats:sup> mice may represent a useful model to test the efficacy of therapeutic interventions on clinical symptoms in addition to declining motor abilities.</jats:p>
  • Zugangsstatus: Freier Zugang