Limits...
Deficiency of antinociception and excessive grooming induced by acute immobilization stress in Per1 mutant mice.

Zhang J, Wu Z, Zhou L, Li H, Teng H, Dai W, Wang Y, Sun ZS - PLoS ONE (2011)

Bottom Line: Another hormonal gene, Oxt, was up-regulated induced by stress in wild-type and Per2 mutant but not in Per1 mutant.In addition, the stress significantly elevated the serum corticosterone levels without genotype-dependent differences, and accordingly the glucocorticoid receptor gene, Nr3c1, expressed with a similar pattern in PVN of all strains.Therefore, our findings suggest a novel functional role of Per1 in neuroendocrine stress system, which further participates in analgesic regulation.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Genetics Centre, Institute of Psychology, Chinese Academy of Sciences, Beijing, People's Republic of China.

ABSTRACT
Acute stressors induce changes in numerous behavioral parameters through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Several important hormones in paraventricular nucleus of the hypothalamus (PVN) play the roles in these stress-induced reactions. Corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) and corticosterone are considered as molecular markers for stress-induced grooming behavior. Oxytocin in PVN is an essential modulator for stress-induced antinociception. The clock gene, Per1, has been identified as an effecter response to the acute stresses, but its function in neuroendocrine stress systems remains unclear. In the present study we observed the alterations in grooming and nociceptive behaviors induced by acute immobilization stress in Per1 mutant mice and other genotypes (wild types and Per2 mutant). The results displayed that stress elicited a more robust effect on grooming behavior in Per1 mutant mice than in other genotypes. Subsequently, the obvious stress-induced antinociception was observed in the wild-type and Per2 mutant mice, however, in Per1 mutant, this antinociceptive effects were partially-reversed (mechanical sensitivity), or over-reversed to hyperalgesia (thermal sensitivity). The real-time qPCR results showed that in PVN, there were stress-induced up-regulations of Crh, Avp and c-fos in all of genotypes; moreover, the expression change of Crh in Per1 mutant mice was much larger than in others. Another hormonal gene, Oxt, was up-regulated induced by stress in wild-type and Per2 mutant but not in Per1 mutant. In addition, the stress significantly elevated the serum corticosterone levels without genotype-dependent differences, and accordingly the glucocorticoid receptor gene, Nr3c1, expressed with a similar pattern in PVN of all strains. Taken together, the present study indicated that in acute stress treated Per1 mutant mice, there are abnormal hormonal responses in PVN, correlating with the aberrant performance of stress-induced behaviors. Therefore, our findings suggest a novel functional role of Per1 in neuroendocrine stress system, which further participates in analgesic regulation.

Show MeSH

Related in: MedlinePlus

Increased serum corticosterone response to immobilization stress in different genotypes.Serum samples were collected from stressed and non-stressed control of wild type, Per1 mutant and Per2 mutant mice, and assayed with the corticosterone ELISA kit. Data shown represent the mean ± SEM of 4 animals from several independent experiments for each data point. The asterisks (*, p<0.05; **, p<0.01, one way ANOVA) indicate in each genotype, the significant differences of corticosterone level between the stressed mice and the non-stressed mice.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3021546&req=5

pone-0016212-g005: Increased serum corticosterone response to immobilization stress in different genotypes.Serum samples were collected from stressed and non-stressed control of wild type, Per1 mutant and Per2 mutant mice, and assayed with the corticosterone ELISA kit. Data shown represent the mean ± SEM of 4 animals from several independent experiments for each data point. The asterisks (*, p<0.05; **, p<0.01, one way ANOVA) indicate in each genotype, the significant differences of corticosterone level between the stressed mice and the non-stressed mice.

Mentions: Since corticosterone, as a major stress hormone in rodents, is quickly up-regulated in response to stress in normal wild type mice [1], we then monitored the serum corticosterone levels in our M-WT mice and Per genes mutant mice under both non-stressed and stressed statuses. As our results shown (Figure 5), in all non-stressed animals serum corticosterone basal levels had no significant differences between M-WT (62.02±8.2 ng/ml), Per1 mutant (52.92±4.8 ng/ml) and Per2 mutant mice (88.34±17.31 ng/ml). Furthermore, after immobilization stress, serum corticosterone levels showed the robust increase in M-WT (186.3±15.5 ng/ml; F = 50.29, p<0.01), Per1 mutant (133.25±13.5 ng/ml; F = 31.5, p<0.01) and Per2 mutant mice (180.9±14.27 ng/ml; F = 17.02, p<0.05). Importantly, there were no significant differences in stress-induced increase fold of serum corticosterone levels between these three genotypes (F = 2.68, p = 0.15).


Deficiency of antinociception and excessive grooming induced by acute immobilization stress in Per1 mutant mice.

Zhang J, Wu Z, Zhou L, Li H, Teng H, Dai W, Wang Y, Sun ZS - PLoS ONE (2011)

Increased serum corticosterone response to immobilization stress in different genotypes.Serum samples were collected from stressed and non-stressed control of wild type, Per1 mutant and Per2 mutant mice, and assayed with the corticosterone ELISA kit. Data shown represent the mean ± SEM of 4 animals from several independent experiments for each data point. The asterisks (*, p<0.05; **, p<0.01, one way ANOVA) indicate in each genotype, the significant differences of corticosterone level between the stressed mice and the non-stressed mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3021546&req=5

pone-0016212-g005: Increased serum corticosterone response to immobilization stress in different genotypes.Serum samples were collected from stressed and non-stressed control of wild type, Per1 mutant and Per2 mutant mice, and assayed with the corticosterone ELISA kit. Data shown represent the mean ± SEM of 4 animals from several independent experiments for each data point. The asterisks (*, p<0.05; **, p<0.01, one way ANOVA) indicate in each genotype, the significant differences of corticosterone level between the stressed mice and the non-stressed mice.
Mentions: Since corticosterone, as a major stress hormone in rodents, is quickly up-regulated in response to stress in normal wild type mice [1], we then monitored the serum corticosterone levels in our M-WT mice and Per genes mutant mice under both non-stressed and stressed statuses. As our results shown (Figure 5), in all non-stressed animals serum corticosterone basal levels had no significant differences between M-WT (62.02±8.2 ng/ml), Per1 mutant (52.92±4.8 ng/ml) and Per2 mutant mice (88.34±17.31 ng/ml). Furthermore, after immobilization stress, serum corticosterone levels showed the robust increase in M-WT (186.3±15.5 ng/ml; F = 50.29, p<0.01), Per1 mutant (133.25±13.5 ng/ml; F = 31.5, p<0.01) and Per2 mutant mice (180.9±14.27 ng/ml; F = 17.02, p<0.05). Importantly, there were no significant differences in stress-induced increase fold of serum corticosterone levels between these three genotypes (F = 2.68, p = 0.15).

Bottom Line: Another hormonal gene, Oxt, was up-regulated induced by stress in wild-type and Per2 mutant but not in Per1 mutant.In addition, the stress significantly elevated the serum corticosterone levels without genotype-dependent differences, and accordingly the glucocorticoid receptor gene, Nr3c1, expressed with a similar pattern in PVN of all strains.Therefore, our findings suggest a novel functional role of Per1 in neuroendocrine stress system, which further participates in analgesic regulation.

View Article: PubMed Central - PubMed

Affiliation: Behavioral Genetics Centre, Institute of Psychology, Chinese Academy of Sciences, Beijing, People's Republic of China.

ABSTRACT
Acute stressors induce changes in numerous behavioral parameters through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Several important hormones in paraventricular nucleus of the hypothalamus (PVN) play the roles in these stress-induced reactions. Corticotropin-releasing hormone (CRH), arginine-vasopressin (AVP) and corticosterone are considered as molecular markers for stress-induced grooming behavior. Oxytocin in PVN is an essential modulator for stress-induced antinociception. The clock gene, Per1, has been identified as an effecter response to the acute stresses, but its function in neuroendocrine stress systems remains unclear. In the present study we observed the alterations in grooming and nociceptive behaviors induced by acute immobilization stress in Per1 mutant mice and other genotypes (wild types and Per2 mutant). The results displayed that stress elicited a more robust effect on grooming behavior in Per1 mutant mice than in other genotypes. Subsequently, the obvious stress-induced antinociception was observed in the wild-type and Per2 mutant mice, however, in Per1 mutant, this antinociceptive effects were partially-reversed (mechanical sensitivity), or over-reversed to hyperalgesia (thermal sensitivity). The real-time qPCR results showed that in PVN, there were stress-induced up-regulations of Crh, Avp and c-fos in all of genotypes; moreover, the expression change of Crh in Per1 mutant mice was much larger than in others. Another hormonal gene, Oxt, was up-regulated induced by stress in wild-type and Per2 mutant but not in Per1 mutant. In addition, the stress significantly elevated the serum corticosterone levels without genotype-dependent differences, and accordingly the glucocorticoid receptor gene, Nr3c1, expressed with a similar pattern in PVN of all strains. Taken together, the present study indicated that in acute stress treated Per1 mutant mice, there are abnormal hormonal responses in PVN, correlating with the aberrant performance of stress-induced behaviors. Therefore, our findings suggest a novel functional role of Per1 in neuroendocrine stress system, which further participates in analgesic regulation.

Show MeSH
Related in: MedlinePlus