Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm-/- knockout mice.

Neurotoxicology and Teratology
Ying ChenCharles V Vorhees

Abstract

Enhanced oxidative stress or deficient oxidative stress response in the brain is associated with neurodegenerative disorders and behavioral abnormalities. Previously we generated a knockout mouse line lacking the gene encoding glutamate-cysteine ligase modifier subunit (GCLM). Gclm(-/-) knockout (KO) mice are viable and fertile, yet exhibit only 9-35% of wild-type levels of reduced glutathione (GSH) in tissues, making them a useful model for chronic GSH depletion. Having the global absence of this gene, KO mice--from the time of conception and throughout postnatal life--experience chronic oxidative stress in all tissues, including brain. Between postnatal day (P) 60 and P100, we carried out behavioral phenotyping tests in adults, comparing male and female Gclm(-/-) with Gclm(-/-) wild-type (WT) littermates. Compared with WT, KO mice exhibited: subnormal anxiety in the elevated zero maze; normal overall exploratory open-field activity, but slightly more activity in the peripheral zones; normal acoustic startle and prepulse inhibition reactions; normal novel object recognition with increased time attending to the stimulus objects; slightly reduced latencies to reach a random marked platform in the Morris water maze; normal spatia...Continue Reading

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Citations

Mar 13, 2014·Current Opinion in Psychiatry·Francesco E EmilianiAkira Sawa
Feb 2, 2013·Trends in Pharmacological Sciences·Michael BerkOlivia M Dean
Sep 24, 2015·Molecular Psychiatry·M A Landek-SalgadoA Sawa
Aug 10, 2018·Aging and Disease·J Thomas MockNathalie Sumien

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