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Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress.

Cole TB, Giordano G, Co AL, Mohar I, Kavanagh TJ, Costa LG - J Toxicol (2011)

Bottom Line: Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain.Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze.However, more subtle alterations, or changes which may appear as animals age, cannot be excluded.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.

ABSTRACT
Glutathione (GSH) is a major player in cellular defense against oxidative stress. Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain. GCLM-knockout (Gclm(-/-)) mice may thus represent a model for compromised response to oxidative stress amenable to in vitro and in vivo investigations. In order to determine whether the diminished GSH content would by itself cause behavioral alterations, a series of behavioral tests were carried out comparing young adult Gclm(-/-) with wild-type mice. Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze. Results showed no differences between Gclm(-/-) and wild-type mice in any of the neurobehavioral tests. However, more subtle alterations, or changes which may appear as animals age, cannot be excluded.

No MeSH data available.


Rotarod. Mice were placed on a rotarod, and latency to fall from the rotarod was recorded for each of 4 successive trials. Trials were separated by a 1 min interval.  Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.
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fig1: Rotarod. Mice were placed on a rotarod, and latency to fall from the rotarod was recorded for each of 4 successive trials. Trials were separated by a 1 min interval. Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.

Mentions: At 13 weeks of age, motor coordination and cerebellar learning were tested using a rotarod (Figure 1). Wild-type and Gclm−/− mice both learned the task, and latency to fall off the rotarod increased with each successive trial (trial 1 versus trials 2, 3, and 4: wild-type, P < .05; Gclm−/−, P < .01). There were no significant differences in latency between Gclm−/− and wild-type mice on trials one (P = .27), two (P = .24), three (P = .13), or four (P = .60), nor when averaging latencies across all four trials (P = .42).


Behavioral Characterization of GCLM-Knockout Mice, a Model for Enhanced Susceptibility to Oxidative Stress.

Cole TB, Giordano G, Co AL, Mohar I, Kavanagh TJ, Costa LG - J Toxicol (2011)

Rotarod. Mice were placed on a rotarod, and latency to fall from the rotarod was recorded for each of 4 successive trials. Trials were separated by a 1 min interval.  Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3090610&req=5

fig1: Rotarod. Mice were placed on a rotarod, and latency to fall from the rotarod was recorded for each of 4 successive trials. Trials were separated by a 1 min interval. Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.
Mentions: At 13 weeks of age, motor coordination and cerebellar learning were tested using a rotarod (Figure 1). Wild-type and Gclm−/− mice both learned the task, and latency to fall off the rotarod increased with each successive trial (trial 1 versus trials 2, 3, and 4: wild-type, P < .05; Gclm−/−, P < .01). There were no significant differences in latency between Gclm−/− and wild-type mice on trials one (P = .27), two (P = .24), three (P = .13), or four (P = .60), nor when averaging latencies across all four trials (P = .42).

Bottom Line: Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain.Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze.However, more subtle alterations, or changes which may appear as animals age, cannot be excluded.

View Article: PubMed Central - PubMed

Affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195, USA.

ABSTRACT
Glutathione (GSH) is a major player in cellular defense against oxidative stress. Deletion of the modifier subunit of glutamate cysteine ligase (GCLM), the first and the rate-limiting enzyme in the synthesis of GSH, leads to significantly lower GSH levels in all tissues including the brain. GCLM-knockout (Gclm(-/-)) mice may thus represent a model for compromised response to oxidative stress amenable to in vitro and in vivo investigations. In order to determine whether the diminished GSH content would by itself cause behavioral alterations, a series of behavioral tests were carried out comparing young adult Gclm(-/-) with wild-type mice. Tests included the rotarod, acoustic startle reflex and prepulse inhibition of the startle reflex, open field behavior, and the platform reversal variant of the Morris Water Maze. Results showed no differences between Gclm(-/-) and wild-type mice in any of the neurobehavioral tests. However, more subtle alterations, or changes which may appear as animals age, cannot be excluded.

No MeSH data available.