TY - JOUR
T1 - Genetic factors mediate the impact of chronic stress and subsequent response to novel acute stress
AU - Terenina, Elena E.
AU - Cavigelli, Sonia
AU - Mormede, Pierre
AU - Zhao, Wenyuan
AU - Parks, Cory
AU - Lu, Lu
AU - Jones, Byron C.
AU - Mulligan, Megan K.
N1 - Funding Information:
This work was supported by funding from National Institutes of Health grant R01AA021951, National Institute on Alcohol Abuse and Alcoholism grant U01AA13499, Internal New Grant Support Funding (E073239005) from the University of Tennessee Health Science Center, and funding from AgreenSkills and the Animal Genetics Division of INRA (France).
Publisher Copyright:
© 2019 Terenina, Cavigelli, Mormede, Zhao, Parks, Lu, Jones and Mulligan.
PY - 2019
Y1 - 2019
N2 - Individual differences in physiological and biobehavioral adaptation to chronic stress are important predictors of health and fitness; genetic differences play an important role in this adaptation. To identify these differences we measured the biometric, neuroendocrine, and transcriptional response to stress among inbred mouse strains with varying degrees of genetic similarity, C57BL/6J (B), C57BL/6NJ (N), and DBA/2J (D). The B and D strains are highly genetically diverse whereas the B and N substrains are highly similar. Strain differences in hypothalamic-pituitary-adrenal (HPA) axis cross-sensitization were determined by plasma corticosterone (CORT) levels and hippocampal gene expression following 7-weeks of chronic mild stress (CMS) or normal housing (NH) and subsequent exposure to novel acute restraint. Fecal CORT metabolites and body and organ weights were also measured. All strains exposed to CMS had reduced heart weights, whereas body weight gain was attenuated only in B and N strains. Acute stress alone produced larger plasma CORT responses in the D and N strains compared to the B strain. CMS paired with acute stress produced cross-sensitization of the CORT response in the N strain. The N strain also had the largest number of hippocampal transcripts with up-regulated expression in response to stress. In contrast, the D strain had the largest number of transcripts with down-regulated expression following CMS and acute stress. In summary, we observed differential responses to CMS at both the physiological and molecular level among genetically diverse strains, indicating that genetic factors drive individual differences in experience-dependent regulation of the stress response.
AB - Individual differences in physiological and biobehavioral adaptation to chronic stress are important predictors of health and fitness; genetic differences play an important role in this adaptation. To identify these differences we measured the biometric, neuroendocrine, and transcriptional response to stress among inbred mouse strains with varying degrees of genetic similarity, C57BL/6J (B), C57BL/6NJ (N), and DBA/2J (D). The B and D strains are highly genetically diverse whereas the B and N substrains are highly similar. Strain differences in hypothalamic-pituitary-adrenal (HPA) axis cross-sensitization were determined by plasma corticosterone (CORT) levels and hippocampal gene expression following 7-weeks of chronic mild stress (CMS) or normal housing (NH) and subsequent exposure to novel acute restraint. Fecal CORT metabolites and body and organ weights were also measured. All strains exposed to CMS had reduced heart weights, whereas body weight gain was attenuated only in B and N strains. Acute stress alone produced larger plasma CORT responses in the D and N strains compared to the B strain. CMS paired with acute stress produced cross-sensitization of the CORT response in the N strain. The N strain also had the largest number of hippocampal transcripts with up-regulated expression in response to stress. In contrast, the D strain had the largest number of transcripts with down-regulated expression following CMS and acute stress. In summary, we observed differential responses to CMS at both the physiological and molecular level among genetically diverse strains, indicating that genetic factors drive individual differences in experience-dependent regulation of the stress response.
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U2 - 10.3389/fnins.2019.00438
DO - 10.3389/fnins.2019.00438
M3 - Article
C2 - 31164799
AN - SCOPUS:85068584739
SN - 1662-4548
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - MAY
M1 - 438
ER -