Effects of aging and fetal tissue transplantation on the patterns of expression of neuroendocrine and neurochemical outputs of the biological clock

Abstract

Circadian rhythmicity is a common physiological phenomenon. Many rhythms change with age. Since the suprachiasmatic nucleus (SCN) is the major neural circadian pacemaker, we hypothesized that changes in the circadian rhythms maybe due to changes in the SCN itself. In this dissertation, I asked two questions: (1) Does age affect the immediate early gene expression in the SCN? If so, can transplantation of fetal tissue containing the SCN restore normal function? (2) Does age change SCN-driven endocrine outputs, such as the hypothalamic-pituitary-adrenal cortex (HPA) axis; If so, can fetal SCN transplants restore normal function? The expression of immediate early genes (IEG), fos and jun, have been used as markers of neural activity in many studies. We used expression of IEG in the SCN as an index of neural activity of the SCN. Using immunocytochemistry, we detected a significant decrease in light-induced Fos and Jun-B expression in the SCN in middle-aged rats, and transplantation of fetal SCN tissue into middle-aged rats partially restored the IEG expression in hosts to that of young rats. We chose to study corticotropin releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in HPA axis. Using in situ hybridization histochemistry and solution hybridization-RNase protection assays, we detected that both diurnal rhythms of CRH mRNA in the paraventricular nucleus (PVN) and POMC mRNA in the anterior pituitary were abolished by the time animals were middle-aged. Transplantation of fetal SCN tissue into middle-aged rats restored a diurnal rhythm of CRH mRNA in the PVN, but the pattern was slightly altered. SCN transplants can restore a diurnal rhythm of POMC mRNA in the anterior pituitary, but the amplitude of the rhythm remained as low as that of middle-aged rats. In conclusion, aging affects rhythms of the SCN and SCN-driven endocrine outputs. These changes may not be permanent, since fetal SCN transplants can partially correct those changes.