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Cysteamine attenuates the decreases in TrkB protein levels and the anxiety/depression-like behaviors in mice induced by corticosterone treatment.

Kutiyanawalla A, Terry AV, Pillai A - PLoS ONE (2011)

Bottom Line: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus.Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Health Behavior, Georgia Health Sciences University, Augusta, Georgia, United States of America.

ABSTRACT

Objective: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders.

Materials and methods: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure.

Results: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.

Conclusions: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.

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Related in: MedlinePlus

Effects of cysteamine in TrkB knockout mice on anxiety-like behaviors as measured in the (A) Open Field test, (B-C) Light/Dark test, (D) Elevated Plus Maze Maze test and (E) Tail Suspension Test.TrkB knock out (KO) and wild type (WT) male mice were treated for 3 weeks with vehicle (water) or cysteamine (CYS; 150 mg/kg/day). (A) Mean total of the time spent in the center for the entire session, (B) % of the time-spent in the lit area, (C) % of the time-spent in the dark area, (D) % of the time in open arms, and (E) the immobility score (in seconds). Values are mean ± SE (n = 6 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle.
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pone-0026153-g009: Effects of cysteamine in TrkB knockout mice on anxiety-like behaviors as measured in the (A) Open Field test, (B-C) Light/Dark test, (D) Elevated Plus Maze Maze test and (E) Tail Suspension Test.TrkB knock out (KO) and wild type (WT) male mice were treated for 3 weeks with vehicle (water) or cysteamine (CYS; 150 mg/kg/day). (A) Mean total of the time spent in the center for the entire session, (B) % of the time-spent in the lit area, (C) % of the time-spent in the dark area, (D) % of the time in open arms, and (E) the immobility score (in seconds). Values are mean ± SE (n = 6 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle.

Mentions: We next examined the role of TrkB in mediating the behavioral effects of cysteamine treatment in mice. In OF, two-way ANOVA with genotype and treatment as the main effects showed no significant main effect of genotype [F(1,18) = 1.329; p = 0.264], treatment [F(1,18) = 0.464; p = 0.504] and genotype x interaction [F(1,18) = 0.0312; p = 0.861]. Post-hoc analysis did not find any significant difference in the time spent in the center between vehicle-treated WT and TrkB KO mice (Fig 9A). The lack of change in open field activity was further tested by examining the ratio of ambulatory distance in center to total distance. TrkB knockout mice did not exhibit any significant change in the above phenotype (data not shown). In addition, we did not find any significant change in the above measures following cysteamine treatment indicating that TrkB knockout mice are not responsive to cysteamine in open field activity.


Cysteamine attenuates the decreases in TrkB protein levels and the anxiety/depression-like behaviors in mice induced by corticosterone treatment.

Kutiyanawalla A, Terry AV, Pillai A - PLoS ONE (2011)

Effects of cysteamine in TrkB knockout mice on anxiety-like behaviors as measured in the (A) Open Field test, (B-C) Light/Dark test, (D) Elevated Plus Maze Maze test and (E) Tail Suspension Test.TrkB knock out (KO) and wild type (WT) male mice were treated for 3 weeks with vehicle (water) or cysteamine (CYS; 150 mg/kg/day). (A) Mean total of the time spent in the center for the entire session, (B) % of the time-spent in the lit area, (C) % of the time-spent in the dark area, (D) % of the time in open arms, and (E) the immobility score (in seconds). Values are mean ± SE (n = 6 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3198436&req=5

pone-0026153-g009: Effects of cysteamine in TrkB knockout mice on anxiety-like behaviors as measured in the (A) Open Field test, (B-C) Light/Dark test, (D) Elevated Plus Maze Maze test and (E) Tail Suspension Test.TrkB knock out (KO) and wild type (WT) male mice were treated for 3 weeks with vehicle (water) or cysteamine (CYS; 150 mg/kg/day). (A) Mean total of the time spent in the center for the entire session, (B) % of the time-spent in the lit area, (C) % of the time-spent in the dark area, (D) % of the time in open arms, and (E) the immobility score (in seconds). Values are mean ± SE (n = 6 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle.
Mentions: We next examined the role of TrkB in mediating the behavioral effects of cysteamine treatment in mice. In OF, two-way ANOVA with genotype and treatment as the main effects showed no significant main effect of genotype [F(1,18) = 1.329; p = 0.264], treatment [F(1,18) = 0.464; p = 0.504] and genotype x interaction [F(1,18) = 0.0312; p = 0.861]. Post-hoc analysis did not find any significant difference in the time spent in the center between vehicle-treated WT and TrkB KO mice (Fig 9A). The lack of change in open field activity was further tested by examining the ratio of ambulatory distance in center to total distance. TrkB knockout mice did not exhibit any significant change in the above phenotype (data not shown). In addition, we did not find any significant change in the above measures following cysteamine treatment indicating that TrkB knockout mice are not responsive to cysteamine in open field activity.

Bottom Line: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus.Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry and Health Behavior, Georgia Health Sciences University, Augusta, Georgia, United States of America.

ABSTRACT

Objective: Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences, have been shown to contribute significantly to the manifestation of anxiety-like behaviors observed in many neuropsychiatric disorders. Brain-derived neurotrophic factor (BDNF) signaling through its receptor TrkB plays an important role in stress-mediated changes in structural as well as functional neuroplasticity. Studies designed to elucidate the mechanisms whereby TrkB signaling is regulated in chronic stress might provide valuable information for the development of new therapeutic strategies for several stress-related psychiatric disorders.

Materials and methods: We examined the potential of cysteamine, a neuroprotective compound to attenuate anxiety and depression like behaviors in a mouse model of anxiety/depression induced by chronic corticosterone exposure.

Results: Cysteamine administration (150 mg/kg/day, through drinking water) for 21 days significantly ameliorated chronic corticosterone-induced decreases in TrkB protein levels in frontal cortex and hippocampus. Furthermore, cysteamine treatment reversed the anxiety and depression like behavioral abnormalities induced by chronic corticosterone treatment. Finally, mice deficient in TrkB, showed a reduced response to cysteamine in behavioral tests, suggesting that TrkB signaling plays an important role in the antidepressant effects of cysteamine.

Conclusions: The animal studies described here highlight the potential use of cysteamine as a novel therapeutic strategy for glucocorticoid-related symptoms of psychiatric disorders.

Show MeSH
Related in: MedlinePlus