Limits...
Environmental Enrichment Reduces Anxiety by Differentially Activating Serotonergic and Neuropeptide Y (NPY)-Ergic System in Indian Field Mouse (Mus booduga): An Animal Model of Post-Traumatic Stress Disorder.

Ragu Varman D, Rajan KE - PLoS ONE (2015)

Bottom Line: Subsequently, the serotonin transporter (SERT) and 5-HT1A receptor were up-regulated significantly, but the same did not occur in the 5-HT2C receptor, which is associated with the activation of calmodulin-dependent protein kinase-II (CaMKII) and a transcription factor cAMP response element binding protein (CREB).Our results show that predator exposure induced the activation of CaMKII/CREB, which is accompanied with increased levels of histone acetylation (H3, H4) and decreased histone deacetylases (HDAC1, 2).Subsequently, in the amygdala, the transcription of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY) and its Y1 receptor were up-regulated, whereas the Y2 receptor was down-regulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science, School of Life Sciences, Bharathidasan University, Palkalaiperur campus, Tiruchirappalli, India.

ABSTRACT
Exposure to a predator elicits an innate fear response and mimics several behavioral disorders related to post-traumatic stress disorder (PTSD). The protective role of an enriched condition (EC) against psychogenic stressors in various animal models has been well documented. However, this condition has not been tested in field mice in the context of PTSD. In this study, we show that field mice (Mus booduga) housed under EC exhibit predominantly proactive and less reactive behavior compared with mice housed under standard conditions (SC) during exposure to their natural predator (field rat Rattus rattus). Furthermore, we observed that EC mice displayed less anxiety-like behavior in an elevated plus maze (EPM) and light/dark-box after exposure to the predator (7 hrs/7 days). In EC mice, predator exposure elevated the level of serotonin (5-Hydroxytrypamine, [5-HT]) in the amygdala as part of the coping response. Subsequently, the serotonin transporter (SERT) and 5-HT1A receptor were up-regulated significantly, but the same did not occur in the 5-HT2C receptor, which is associated with the activation of calmodulin-dependent protein kinase-II (CaMKII) and a transcription factor cAMP response element binding protein (CREB). Our results show that predator exposure induced the activation of CaMKII/CREB, which is accompanied with increased levels of histone acetylation (H3, H4) and decreased histone deacetylases (HDAC1, 2). Subsequently, in the amygdala, the transcription of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY) and its Y1 receptor were up-regulated, whereas the Y2 receptor was down-regulated. Therefore, EC facilitated a coping response against a fear associated cue in a PTSD animal model and reduced anxiety by differentially activating serotonergic and NPY-ergic systems.

No MeSH data available.


Related in: MedlinePlus

Effect of environmental enrichment on activation of SERT and 5-HT level in mice exposed to predator.(a) Representative western blots shows the level of SERT (70 kDa) and β-actin (43 kDa). (b) There was a significant increase in 5-HT level after exposure to predator in STSC, LTSC and EC mice. (C) SERT protein level was significantly increased in EC following predator exposure than STSC and LTSC mice. Data were shown as mean ± SEM, * indicates significant difference (*P < 0.05; **P < 0.01; ***P < 0.001), respect to comparison between groups (a = STSC verses LTSC; b = LTSC verses EC; c = STSC verses EC). Raw data is provided in S2 Data.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4446351&req=5

pone.0127945.g004: Effect of environmental enrichment on activation of SERT and 5-HT level in mice exposed to predator.(a) Representative western blots shows the level of SERT (70 kDa) and β-actin (43 kDa). (b) There was a significant increase in 5-HT level after exposure to predator in STSC, LTSC and EC mice. (C) SERT protein level was significantly increased in EC following predator exposure than STSC and LTSC mice. Data were shown as mean ± SEM, * indicates significant difference (*P < 0.05; **P < 0.01; ***P < 0.001), respect to comparison between groups (a = STSC verses LTSC; b = LTSC verses EC; c = STSC verses EC). Raw data is provided in S2 Data.

Mentions: We determined the level of 5-HT, expression level of SERT, 5-HT1A and 5-HT2C in the mice housed in various environmental conditions and exposed to a predator. As shown in Fig 4A, basal levels of 5-HT were significantly affected by exposure (F1,35 = 1811.16; P<0.001), housing condition (F2,35 = 431.95; P<0.001) and interaction of exposure × housing condition (F2,35 = 147.85; P<0.001). Further, Bonferroni test revealed that the 5-HT level was significantly higher in EC mice (P<0.001) and STSC mice (P<0.001) than LTSC mice. In comparison, elevated levels of 5-HT were significantly higher in STSC mice than LTSC mice (P<0.001).


Environmental Enrichment Reduces Anxiety by Differentially Activating Serotonergic and Neuropeptide Y (NPY)-Ergic System in Indian Field Mouse (Mus booduga): An Animal Model of Post-Traumatic Stress Disorder.

Ragu Varman D, Rajan KE - PLoS ONE (2015)

Effect of environmental enrichment on activation of SERT and 5-HT level in mice exposed to predator.(a) Representative western blots shows the level of SERT (70 kDa) and β-actin (43 kDa). (b) There was a significant increase in 5-HT level after exposure to predator in STSC, LTSC and EC mice. (C) SERT protein level was significantly increased in EC following predator exposure than STSC and LTSC mice. Data were shown as mean ± SEM, * indicates significant difference (*P < 0.05; **P < 0.01; ***P < 0.001), respect to comparison between groups (a = STSC verses LTSC; b = LTSC verses EC; c = STSC verses EC). Raw data is provided in S2 Data.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4446351&req=5

pone.0127945.g004: Effect of environmental enrichment on activation of SERT and 5-HT level in mice exposed to predator.(a) Representative western blots shows the level of SERT (70 kDa) and β-actin (43 kDa). (b) There was a significant increase in 5-HT level after exposure to predator in STSC, LTSC and EC mice. (C) SERT protein level was significantly increased in EC following predator exposure than STSC and LTSC mice. Data were shown as mean ± SEM, * indicates significant difference (*P < 0.05; **P < 0.01; ***P < 0.001), respect to comparison between groups (a = STSC verses LTSC; b = LTSC verses EC; c = STSC verses EC). Raw data is provided in S2 Data.
Mentions: We determined the level of 5-HT, expression level of SERT, 5-HT1A and 5-HT2C in the mice housed in various environmental conditions and exposed to a predator. As shown in Fig 4A, basal levels of 5-HT were significantly affected by exposure (F1,35 = 1811.16; P<0.001), housing condition (F2,35 = 431.95; P<0.001) and interaction of exposure × housing condition (F2,35 = 147.85; P<0.001). Further, Bonferroni test revealed that the 5-HT level was significantly higher in EC mice (P<0.001) and STSC mice (P<0.001) than LTSC mice. In comparison, elevated levels of 5-HT were significantly higher in STSC mice than LTSC mice (P<0.001).

Bottom Line: Subsequently, the serotonin transporter (SERT) and 5-HT1A receptor were up-regulated significantly, but the same did not occur in the 5-HT2C receptor, which is associated with the activation of calmodulin-dependent protein kinase-II (CaMKII) and a transcription factor cAMP response element binding protein (CREB).Our results show that predator exposure induced the activation of CaMKII/CREB, which is accompanied with increased levels of histone acetylation (H3, H4) and decreased histone deacetylases (HDAC1, 2).Subsequently, in the amygdala, the transcription of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY) and its Y1 receptor were up-regulated, whereas the Y2 receptor was down-regulated.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Science, School of Life Sciences, Bharathidasan University, Palkalaiperur campus, Tiruchirappalli, India.

ABSTRACT
Exposure to a predator elicits an innate fear response and mimics several behavioral disorders related to post-traumatic stress disorder (PTSD). The protective role of an enriched condition (EC) against psychogenic stressors in various animal models has been well documented. However, this condition has not been tested in field mice in the context of PTSD. In this study, we show that field mice (Mus booduga) housed under EC exhibit predominantly proactive and less reactive behavior compared with mice housed under standard conditions (SC) during exposure to their natural predator (field rat Rattus rattus). Furthermore, we observed that EC mice displayed less anxiety-like behavior in an elevated plus maze (EPM) and light/dark-box after exposure to the predator (7 hrs/7 days). In EC mice, predator exposure elevated the level of serotonin (5-Hydroxytrypamine, [5-HT]) in the amygdala as part of the coping response. Subsequently, the serotonin transporter (SERT) and 5-HT1A receptor were up-regulated significantly, but the same did not occur in the 5-HT2C receptor, which is associated with the activation of calmodulin-dependent protein kinase-II (CaMKII) and a transcription factor cAMP response element binding protein (CREB). Our results show that predator exposure induced the activation of CaMKII/CREB, which is accompanied with increased levels of histone acetylation (H3, H4) and decreased histone deacetylases (HDAC1, 2). Subsequently, in the amygdala, the transcription of brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY) and its Y1 receptor were up-regulated, whereas the Y2 receptor was down-regulated. Therefore, EC facilitated a coping response against a fear associated cue in a PTSD animal model and reduced anxiety by differentially activating serotonergic and NPY-ergic systems.

No MeSH data available.


Related in: MedlinePlus