Reduced corticotropin-releasing factor and enhanced vasopressin gene expression in brains of mice with autoimmunity-induced behavioral dysfunction

The spontaneous development of autoimmune disease in MRL-1pr mice induces b ehavioral and endocrine changes that resemble effects of chronic stressors. To further examine the correspondence between autoimmune disease and chron ic stress, we asked whether the brains of autoimmune mice show a shift in t he corticotropin-releasing factor (CRF) to vasopressin (AVP) ratio. Using i n situ hybridization histochemistry with S-35-labelled mouse riboprobes, th e levels of mRNA transcripts encoding CRF and AVP were compared between aut oimmune MRL-1pr and control MRL +/+ brains. CRF transcript levels were lowe r in the hypothalamic paraventricular nucleus and in the central nucleus of the amygdala in MRL-1pr mice. AVP transcript levels were higher in the par aventricular and the supraoptic nuclei in MRL-1pr mice compared to controls . CRF mRNA levels were inversely related to performance in stress-sensitive tasks and to measures of autoimmunity. As found previously for behavioral performance, immunosuppressive treatment with cyclophosphamide abolished th e group difference in neuropeptide gene expression. These results indicate that an autoimmune disease process is necessary for the shift in the brain CRF:AVP ratio. Furthermore, they support the parallel between chronic stres s and chronic autoimmunity/inflammation, and suggest common central mechani sms relevant to endocrine function and behavior. (C) 1999 Elsevier Science B.V. All rights reserved.