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 proBDNF and mature BDNF (mBDNF) protein levels in the frontal cortex and hippocampus.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 corticosterone treatment. proBDNF and mBDNF protein levels were determined in the (A) frontal cortex and (B) hippocampus by Western blot analysis. The upper panels shows a representative autoradiogram of proBDNF and mBDNF and the lower panel represents the fold change in optical density values normalized to vehicle-treated controls. β-actin was used as a protein loading control. Values are mean ± SE (n = 6 mice per group). (C) BDNF protein levels as measured by ELISA in frontal cortex samples from mice treated with vehicle or cysteamine for 3 weeks as above. Data represent the fold change in BDNF protein levels (pg/mg protein) normalized to vehicle-treated controls. Values are mean ± SE (n = 5 mice per group).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3198436&req=5

pone-0026153-g006: Effects of cysteamine in chronic corticosterone-treated mice on proBDNF and mature BDNF (mBDNF) protein levels in the frontal cortex and hippocampus.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 corticosterone treatment. proBDNF and mBDNF protein levels were determined in the (A) frontal cortex and (B) hippocampus by Western blot analysis. The upper panels shows a representative autoradiogram of proBDNF and mBDNF and the lower panel represents the fold change in optical density values normalized to vehicle-treated controls. β-actin was used as a protein loading control. Values are mean ± SE (n = 6 mice per group). (C) BDNF protein levels as measured by ELISA in frontal cortex samples from mice treated with vehicle or cysteamine for 3 weeks as above. Data represent the fold change in BDNF protein levels (pg/mg protein) normalized to vehicle-treated controls. Values are mean ± SE (n = 5 mice per group).

Mentions: We also determined whether treatment with corticosterone and/or cysteamine in mice alters BDNF levels in frontal cortex and hippocampus. We measured BDNF protein levels using western blots instead of routine ELISA methods to determine the difference in proBDNF and mature BDNF protein levels. Two-way ANOVA on proBDNF levels in the frontal cortex did not find any significant main effect of pretreatment [F(1,18) = 0.0604; p = 0.808], treatment [F(1,18) = 1.4; p = 0.253] and pretreatment x treatment interaction [F(1,18) = 0.219; p = 0.645]. Similarly, the data on mature BDNF levels in frontal cortex did not yield significant main effect of pretreatment [F(1,18) = 0.0062; p = 0.938], treatment [F(1,18) = 1.05; p = 0.318] and pretreatment x treatment interaction [F(1,18) = 0.0165; p = 0.899]. Two-way ANOVA revealed a significant main effect of treatment [F(1,18) = 5.77; p<0.01] on proBDNF levels in hippocampus, but no effect of pretreatment [F(1,18) = 1.709; p = 0.208] and pretreatment x treatment interaction [F(1,18) = 0.348; p = 0.562]. We did not find any significant main effect of pretreatment [F(1,18) = 0.513; p = 0.483], treatment [F(1,18) = 0.0645; p = 0.802] and pretreatment x treatment interaction [F(1,18) = 0.696; p = 0.415] on BDNF levels in hippocampus. Post-hoc analysis did not show any significant change in proBDNF and mature BDNF protein levels in corticosterone or corticosterone plus cysteamine treated mice as compared to vehicle-treated mice in frontal cortex and hippocampus (Fig 6). Since we did not find any change in BDNF protein levels in western blot analysis, we further examined the BDNF levels by ELISA using frontal cortex tissue samples from mice treated with vehicle or cysteamine for 3 weeks. We did not find any significant change in BDNF levels between vehicle and cysteamine treated groups (Fig 6C). We also examined the effects of cysteamine on plasma corticosterone levels. As we reported earlier [16], we found a significant decrease in plasma corticosterone levels following corticosterone treatment. However, cysteamine had no effect on plasma corticosterone levels in vehicle-treated and corticosterone-treated mice (data not shown).


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 proBDNF and mature BDNF (mBDNF) protein levels in the frontal cortex and hippocampus.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 corticosterone treatment. proBDNF and mBDNF protein levels were determined in the (A) frontal cortex and (B) hippocampus by Western blot analysis. The upper panels shows a representative autoradiogram of proBDNF and mBDNF and the lower panel represents the fold change in optical density values normalized to vehicle-treated controls. β-actin was used as a protein loading control. Values are mean ± SE (n = 6 mice per group). (C) BDNF protein levels as measured by ELISA in frontal cortex samples from mice treated with vehicle or cysteamine for 3 weeks as above. Data represent the fold change in BDNF protein levels (pg/mg protein) normalized to vehicle-treated controls. Values are mean ± SE (n = 5 mice per group).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0026153-g006: Effects of cysteamine in chronic corticosterone-treated mice on proBDNF and mature BDNF (mBDNF) protein levels in the frontal cortex and hippocampus.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 corticosterone treatment. proBDNF and mBDNF protein levels were determined in the (A) frontal cortex and (B) hippocampus by Western blot analysis. The upper panels shows a representative autoradiogram of proBDNF and mBDNF and the lower panel represents the fold change in optical density values normalized to vehicle-treated controls. β-actin was used as a protein loading control. Values are mean ± SE (n = 6 mice per group). (C) BDNF protein levels as measured by ELISA in frontal cortex samples from mice treated with vehicle or cysteamine for 3 weeks as above. Data represent the fold change in BDNF protein levels (pg/mg protein) normalized to vehicle-treated controls. Values are mean ± SE (n = 5 mice per group).
Mentions: We also determined whether treatment with corticosterone and/or cysteamine in mice alters BDNF levels in frontal cortex and hippocampus. We measured BDNF protein levels using western blots instead of routine ELISA methods to determine the difference in proBDNF and mature BDNF protein levels. Two-way ANOVA on proBDNF levels in the frontal cortex did not find any significant main effect of pretreatment [F(1,18) = 0.0604; p = 0.808], treatment [F(1,18) = 1.4; p = 0.253] and pretreatment x treatment interaction [F(1,18) = 0.219; p = 0.645]. Similarly, the data on mature BDNF levels in frontal cortex did not yield significant main effect of pretreatment [F(1,18) = 0.0062; p = 0.938], treatment [F(1,18) = 1.05; p = 0.318] and pretreatment x treatment interaction [F(1,18) = 0.0165; p = 0.899]. Two-way ANOVA revealed a significant main effect of treatment [F(1,18) = 5.77; p<0.01] on proBDNF levels in hippocampus, but no effect of pretreatment [F(1,18) = 1.709; p = 0.208] and pretreatment x treatment interaction [F(1,18) = 0.348; p = 0.562]. We did not find any significant main effect of pretreatment [F(1,18) = 0.513; p = 0.483], treatment [F(1,18) = 0.0645; p = 0.802] and pretreatment x treatment interaction [F(1,18) = 0.696; p = 0.415] on BDNF levels in hippocampus. Post-hoc analysis did not show any significant change in proBDNF and mature BDNF protein levels in corticosterone or corticosterone plus cysteamine treated mice as compared to vehicle-treated mice in frontal cortex and hippocampus (Fig 6). Since we did not find any change in BDNF protein levels in western blot analysis, we further examined the BDNF levels by ELISA using frontal cortex tissue samples from mice treated with vehicle or cysteamine for 3 weeks. We did not find any significant change in BDNF levels between vehicle and cysteamine treated groups (Fig 6C). We also examined the effects of cysteamine on plasma corticosterone levels. As we reported earlier [16], we found a significant decrease in plasma corticosterone levels following corticosterone treatment. However, cysteamine had no effect on plasma corticosterone levels in vehicle-treated and corticosterone-treated mice (data not shown).

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