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Amyotrophic lateral sclerosis involves the rapid degeneration of upper and lower motor neurons leading to weakening and paralysis of voluntary movements. Mutations in copper-zinc superoxide dismutase 1 (SOD1) are a known genetic cause of ALS and the SOD1 mouse has been used extensively to investigate molecular mechanisms in ALS. In recent years, evidence suggests that amyotrophic lateral sclerosis and frontotemporal dementia form a spectrum disorder ranging from motor to cognitive dysfunctions. Thus, we tested male and female SOD1 mice for the first time prior to the onset of debilitating motor impairments in behavioural domains relevant to both amyotrophic lateral sclerosis and frontotemporal dementia. SOD1 males displayed reduced locomotion, exploration and increased anxiety-like behaviours compared to control males. Intermediate-term spatial memory was impaired in SOD1 females, while long-term spatial memory deficits as well as lower acoustic startle response and prepulse inhibition were identified in SOD1 mice of both sexes compared to respective controls. Interestingly, SOD1 males exhibited an increased conditioned cue freezing response. Nosing behaviours were also elevated in both male and female SOD1 when assessed in social paradigms. In conclusion, SOD1 mice exhibit a variety of sex-specific behavioural deficits beyond motor impairments supporting the notion of an amyotrophic lateral sclerosis-frontotemporal spectrum disorder. Thus, SOD1 mice may represent a useful model to test the efficacy of therapeutic interventions on clinical symptoms in addition to declining motor abilities. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: Genes, brain, and behavior
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A superoxide dismutase (SOD1) that requires copper and zinc ions for its activity to destroy SUPEROXIDE FREE RADICALS within the CYTOPLASM. Mutations in the SOD1 gene are associated with AMYOTROPHIC LATERAL SCLEROSIS-1.
An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 18.104.22.168.
Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.
An inherited disorder of copper metabolism transmitted as an X-linked trait and characterized by the infantile onset of HYPOTHERMIA, feeding difficulties, hypotonia, SEIZURES, bony deformities, pili torti (twisted hair), and severely impaired intellectual development. Defective copper transport across plasma and endoplasmic reticulum membranes results in copper being unavailable for the synthesis of several copper containing enzymes, including PROTEIN-LYSINE 6-OXIDASE; CERULOPLASMIN; and SUPEROXIDE DISMUTASE. Pathologic changes include defects in arterial elastin, neuronal loss, and gliosis. (From Menkes, Textbook of Child Neurology, 5th ed, p125)
A flavoprotein enzyme that catalyzes the univalent reduction of OXYGEN using NADPH as an electron donor to create SUPEROXIDE ANION. The enzyme is dependent on a variety of CYTOCHROMES. Defects in the production of superoxide ions by enzymes such as NADPH oxidase result in GRANULOMATOUS DISEASE, CHRONIC.
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