TY - JOUR
T1 - The effect of short-term stress on serotonin gene expression in high and low resilient macaques
AU - Bethea, Cynthia L.
AU - Phu, Kenny
AU - Reddy, Arubala P.
AU - Cameron, Judy L.
N1 - Funding Information:
This study was supported by NIH grants HD62618 to JLC and CLB, P30-NS06180 to Dr. Sue Aicher, and RR000163 for the operation of ONPRC. The authors would like to thank Skyla Herod, PhD, Department of Biology and Chemistry, Azusa Pacific University, Los Angeles, CA for the characterization of the monkeys and for performing the termination protocol and brain perfusion. In addition, we thank Aaron Kim for his careful sectioning of the dorsal raphe. We also thank Yibing Ja, M.S ONPRC Cell and Molecular Biology Core, for cloning and sequencing of the new SERT and 5HT1A cDNAs. The authors are indebted to the Division of Animal Resources at ONPRC for the excellent animal husbandry provided for the monkeys in this study. The assistance of the ONPRC Surgical Staff and Pathology Staff and the Endocrine Services Laboratory at ONPRC were also invaluable.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. When stressed with a paradigm of relocation and diet for 60. days, or 2 menstrual cycles, highly stress resilient monkeys continue to ovulate during both stress cycles (HSR); medium stress resilient monkeys ovulate once (MSR) and stress sensitive monkeys do not ovulate for the entire 60. days (SS). This study examines serotonin-related gene expression in monkeys with different sensitivity to stress and exposed to 5. days of moderate stress. Monkeys were first characterized as HSR, MSR or SS. After resumption of menstrual cycles, each monkey was re-stressed for 5. days in the early follicular phase. The expression of 3 genes pivotal to serotonin neural function was assessed in the 3 groups of monkeys (n. =4-5/group). Tryptophan hydroxylase 2 (TPH2), the serotonin reuptake transporter (SERT), and the 5HT1A autoreceptor mRNAs expression were determined at 4 morphological levels of the dorsal raphe nucleus with in situ hybridization (ISH) using digoxigenin-incorporated riboprobes. In addition, cFos was examined with immunohistochemistry. Positive pixel area and/or cell number were measured. All data were analyzed with ANOVA (3 groups) and with a t-test (2 groups). After 5. days of stress, TPH2, SERT, 5HT1A and cFos were significantly lower in the SS group than the HSR group (p. <. 0.05, all). This pattern of expression was the same as the pattern observed in the absence of stress in previous studies. Therefore, the ratio of the HSR/SS expression of each serotonergic gene was calculated in the presence and absence of stress. There was little or no difference in the ratio of HSR/SS gene expression in the presence or absence of stress. Moreover, cFos expression indicates that overall, cell activation in the dorsal raphe nucleus and periaquaductal gray is lower in SS than HSR animals. These data suggest that the serotonin system may set the sensitivity or resilience of the individual, but serotonin-related gene expression may not rapidly respond to moderate stress in nonhuman primates.
AB - Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. When stressed with a paradigm of relocation and diet for 60. days, or 2 menstrual cycles, highly stress resilient monkeys continue to ovulate during both stress cycles (HSR); medium stress resilient monkeys ovulate once (MSR) and stress sensitive monkeys do not ovulate for the entire 60. days (SS). This study examines serotonin-related gene expression in monkeys with different sensitivity to stress and exposed to 5. days of moderate stress. Monkeys were first characterized as HSR, MSR or SS. After resumption of menstrual cycles, each monkey was re-stressed for 5. days in the early follicular phase. The expression of 3 genes pivotal to serotonin neural function was assessed in the 3 groups of monkeys (n. =4-5/group). Tryptophan hydroxylase 2 (TPH2), the serotonin reuptake transporter (SERT), and the 5HT1A autoreceptor mRNAs expression were determined at 4 morphological levels of the dorsal raphe nucleus with in situ hybridization (ISH) using digoxigenin-incorporated riboprobes. In addition, cFos was examined with immunohistochemistry. Positive pixel area and/or cell number were measured. All data were analyzed with ANOVA (3 groups) and with a t-test (2 groups). After 5. days of stress, TPH2, SERT, 5HT1A and cFos were significantly lower in the SS group than the HSR group (p. <. 0.05, all). This pattern of expression was the same as the pattern observed in the absence of stress in previous studies. Therefore, the ratio of the HSR/SS expression of each serotonergic gene was calculated in the presence and absence of stress. There was little or no difference in the ratio of HSR/SS gene expression in the presence or absence of stress. Moreover, cFos expression indicates that overall, cell activation in the dorsal raphe nucleus and periaquaductal gray is lower in SS than HSR animals. These data suggest that the serotonin system may set the sensitivity or resilience of the individual, but serotonin-related gene expression may not rapidly respond to moderate stress in nonhuman primates.
KW - Amenorrhea
KW - Macaques
KW - Ovulation
KW - Serotonin
KW - Stress
KW - Stress resilient
UR - http://www.scopus.com/inward/record.url?scp=84875273820&partnerID=8YFLogxK
U2 - 10.1016/j.pnpbp.2013.01.013
DO - 10.1016/j.pnpbp.2013.01.013
M3 - Article
C2 - 23357537
AN - SCOPUS:84875273820
SN - 0278-5846
VL - 44
SP - 143
EP - 153
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
ER -