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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.


Prepulse inhibition/startle. Auditory startle response was measured using a startle chamber.  Startle amplitude was similar in wild-type and Gclm−/− mice, and a 70 dB prepulse inhibited the subsequent startle response to a similar extent in wild-type and Gclm−/− mice. Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.
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fig2: Prepulse inhibition/startle. Auditory startle response was measured using a startle chamber. Startle amplitude was similar in wild-type and Gclm−/− mice, and a 70 dB prepulse inhibited the subsequent startle response to a similar extent in wild-type and Gclm−/− mice. Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.

Mentions: Auditory startle and prepulse inhibition of startle were tested at 12 weeks of age (Figure 2). There were no differences in auditory startle amplitude (P = .27) between wild-type and Gclm−/− mice. When the 120 dB auditory stimulus was preceded by a 70 dB prepulse, the startle amplitude was significantly reduced (P < .05) in both wild-type and Gclm−/− mice (Figure 2). There were no differences between wild-type and Gclm−/− mice in the magnitude of this prepulse inhibition of startle (P = .28). Latencies to maximum startle were also similar in wild-type and Gclm−/− mice for both auditory startle (22.6 ± 1.8 msec and 20.8 ± 1.5 msec, resp.; P = .46) and prepulse inhibition of startle (31.9 ± 4.2 msec and 25.9 ± 1.8 msec, resp.; P = .18).


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)

Prepulse inhibition/startle. Auditory startle response was measured using a startle chamber.  Startle amplitude was similar in wild-type and Gclm−/− mice, and a 70 dB prepulse inhibited the subsequent startle response to a similar extent in wild-type and Gclm−/− mice. 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

fig2: Prepulse inhibition/startle. Auditory startle response was measured using a startle chamber. Startle amplitude was similar in wild-type and Gclm−/− mice, and a 70 dB prepulse inhibited the subsequent startle response to a similar extent in wild-type and Gclm−/− mice. Results are shown as mean ± SE (n = 12-13). WT: wild-type mice; GCLM-KO: Gclm−/− mice.
Mentions: Auditory startle and prepulse inhibition of startle were tested at 12 weeks of age (Figure 2). There were no differences in auditory startle amplitude (P = .27) between wild-type and Gclm−/− mice. When the 120 dB auditory stimulus was preceded by a 70 dB prepulse, the startle amplitude was significantly reduced (P < .05) in both wild-type and Gclm−/− mice (Figure 2). There were no differences between wild-type and Gclm−/− mice in the magnitude of this prepulse inhibition of startle (P = .28). Latencies to maximum startle were also similar in wild-type and Gclm−/− mice for both auditory startle (22.6 ± 1.8 msec and 20.8 ± 1.5 msec, resp.; P = .46) and prepulse inhibition of startle (31.9 ± 4.2 msec and 25.9 ± 1.8 msec, resp.; P = .18).

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.