Limits...
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.

Show MeSH

Related in: MedlinePlus

Effects of cysteamine in chronic corticosterone-treated mice on anxiety-like behaviors as measured in the (A-B) Light/Dark test, (C) Elevated Plus Maze Maze test and (D) Tail Suspension Test.CD-1 male mice were treated for 7 weeks with vehicle (0.45% hydroxypropyl-β-cyclodextrin) or corticosterone (CORT; 35 ug/ml) in the presence or absence of cysteamine (CYS; 150 mg/kg/day) during the last three weeks of the corticosterone treatment. (A) % of the time spent in the dark area, (B) % of the time spent in the lit area; (B) % of the number of entries in the open arms, and (D) the immobility score (in seconds). Values are mean ± SE (n = 8–9 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle and #p<0.05 versus CORT.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198436&req=5

pone-0026153-g008: Effects of cysteamine in chronic corticosterone-treated mice on anxiety-like behaviors as measured in the (A-B) Light/Dark test, (C) Elevated Plus Maze Maze test and (D) Tail Suspension Test.CD-1 male mice were treated for 7 weeks with vehicle (0.45% hydroxypropyl-β-cyclodextrin) or corticosterone (CORT; 35 ug/ml) in the presence or absence of cysteamine (CYS; 150 mg/kg/day) during the last three weeks of the corticosterone treatment. (A) % of the time spent in the dark area, (B) % of the time spent in the lit area; (B) % of the number of entries in the open arms, and (D) the immobility score (in seconds). Values are mean ± SE (n = 8–9 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle and #p<0.05 versus CORT.

Mentions: In Light/Dark Box Assessment, statistical analysis by two-way ANOVA provided the following results in the time spent in the brightly lit area, main effect of pretreatment, [F(1,30) = 20.97; p<0.0001]; treatment[F(1,30) = 19.25; p<0.0001], and pretreatment x treatment interaction, [F(1,30) = 0.0359; p = 0.851]]. Data on the time spent in the dark area showed a significant main effect of pretreatment [F(1,30) = 34.53; p<0.0001] and treatment [F(1,30) = 21.32; p<0.0001], but no significant effect of pretreatment x treatment interaction [F(1,30) = 1.143; p = 0.2943]. Post hoc analyses indicated that corticosterone treated mice spent significantly more time in the dark (Fig 8A; p<0.05) and less time in the brightly lit zone (Fig 8B; p<0.05) when compared to vehicle controls. Further, this increased preference for the dark zone was reversed by cysteamine treatment (p<0.05), again indicating that cysteamine attenuated the pro-anxiety effects of corticosterone.


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 chronic corticosterone-treated mice on anxiety-like behaviors as measured in the (A-B) Light/Dark test, (C) Elevated Plus Maze Maze test and (D) Tail Suspension Test.CD-1 male mice were treated for 7 weeks with vehicle (0.45% hydroxypropyl-β-cyclodextrin) or corticosterone (CORT; 35 ug/ml) in the presence or absence of cysteamine (CYS; 150 mg/kg/day) during the last three weeks of the corticosterone treatment. (A) % of the time spent in the dark area, (B) % of the time spent in the lit area; (B) % of the number of entries in the open arms, and (D) the immobility score (in seconds). Values are mean ± SE (n = 8–9 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle and #p<0.05 versus CORT.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198436&req=5

pone-0026153-g008: Effects of cysteamine in chronic corticosterone-treated mice on anxiety-like behaviors as measured in the (A-B) Light/Dark test, (C) Elevated Plus Maze Maze test and (D) Tail Suspension Test.CD-1 male mice were treated for 7 weeks with vehicle (0.45% hydroxypropyl-β-cyclodextrin) or corticosterone (CORT; 35 ug/ml) in the presence or absence of cysteamine (CYS; 150 mg/kg/day) during the last three weeks of the corticosterone treatment. (A) % of the time spent in the dark area, (B) % of the time spent in the lit area; (B) % of the number of entries in the open arms, and (D) the immobility score (in seconds). Values are mean ± SE (n = 8–9 mice per group). Bonferroni's post hoc test. *p<0.05 versus vehicle and #p<0.05 versus CORT.
Mentions: In Light/Dark Box Assessment, statistical analysis by two-way ANOVA provided the following results in the time spent in the brightly lit area, main effect of pretreatment, [F(1,30) = 20.97; p<0.0001]; treatment[F(1,30) = 19.25; p<0.0001], and pretreatment x treatment interaction, [F(1,30) = 0.0359; p = 0.851]]. Data on the time spent in the dark area showed a significant main effect of pretreatment [F(1,30) = 34.53; p<0.0001] and treatment [F(1,30) = 21.32; p<0.0001], but no significant effect of pretreatment x treatment interaction [F(1,30) = 1.143; p = 0.2943]. Post hoc analyses indicated that corticosterone treated mice spent significantly more time in the dark (Fig 8A; p<0.05) and less time in the brightly lit zone (Fig 8B; p<0.05) when compared to vehicle controls. Further, this increased preference for the dark zone was reversed by cysteamine treatment (p<0.05), again indicating that cysteamine attenuated the pro-anxiety effects of corticosterone.

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