In young animals, the suprachiasmatic nuclei (SCN) of the hypothalamus, which are critical circadian pacemakers, exhibit a light-induced diurnal rhythm in Fos expression. The expression of this immediate-early gene has been used as an index of the activity of the SCN and their ability to respond to external cues that entrain them, such as light. In the present study, we show that by the time rats reach middle age baseline Fos expression increases prematurely during the dark and that light-induced Fos expression is blunted and delayed. We also demonstrate that transplantation of fetal tissue containing the SCN into the third cerebral ventricle of middle-aged rats enables aged hosts to regain the ability to exhibit diurnal patterns of Fos expression that are strikingly similar to those observed in young animals. Our findings lead to the following conclusions: 1) the diurnal pattern of activity of SCN cells is blunted in middle-aged rats, and 2) SCN transplants provide unique signals that enable the cellular systems of the host to regain rhythmic functional capabilities. These results provide new insights into the critical active role that the host plays in restoration of function evoked by the presence of a transplant.

Aging is associated with a loss of cyclic gonadotropin release in female animals. This deficit may reflect dampened circadian rhythmicity of neuroendocrine events and/or altered function in hypothalamic nuclei important to regulation of cyclic female reproduction. The purpose of this study was to determine if diurnal periodicity and glucose metabolism in the hypothalamus are altered with age and whether such changes could help to explain the age-related deficits in gonadotropin release. Young (3-4-month-old) and old (18-21-month-old) rats were ovariectomized and subjected to the 2-deoxy-D-1-14C-glucose technique to measure rates of cerebral glucose utilization (GU), an index of neural function (Sokoloff et al., 1977) in various brain areas and in the pineal gland. We measured GU during the light (1400 hours) and the dark (2200 hours) in 17 anatomical regions including the following hypothalamic areas: medial preoptic nucleus, suprachiasmatic preoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, arcuate nucleus, and median eminence. Serum concentrations of luteinizing hormone (LH) and prolactin were measured in the same rats to determine the effect of age on both of these hormones. Diurnal periodicity of GU was observed in the suprachiasmatic nucleus and the pineal gland in young and old rats. Although there was no age difference in GU of the pineal gland, GU was reduced during the light and dark in the suprachiasmatic nucleus and all other hypothalamic areas examined except the suprachiasmatic preoptic nucleus and the median eminence. Ovariectomy induced an attenuated increase in concentrations of LH in old, compared to young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

During aging in female rats the estrous cycle ceases and the animals develop phases of constant estrous (CE) or constant diestrous (CD) prior to the irreversible transition into anestrous. In young rats, gamma-aminobutyric acid (GABA) is of pivotal importance for the release of GnRH. In the medial-preoptic area (MPO) where the majority of the GnRH perikarya are located in the rat, GABA release decreases at the time of the preovulatory LH surge. The suprachiasmatic nucleus (SCN) contains numerous GABA neurons. Neurochemical signals from this hypothalamic nucleus provide temporal information to GnRH neurons and thereby influence the preovulatory LH surge and the length of estrous cycles. To investigate aging-related changes of the activity of hypothalamic GABAergic neurons, we determined GABA turnover rates in various hypothalamic nuclei of CE and CD rats and compared them to those determined in young estrous (E) or diestrous rats (D1). In old female rats, GABA activity in the MPO was significantly decreased compared to E and D1 rats. A selective increase of GABA turnover rates was observed in the SCN of CE animals. No age-related changes were observed in the other examined brain areas. These data provide the first evidence for alterations in GABAergic activity in specific hypothalamic areas that depend on age and reproductive status. These may cause changes in ability to induce preovulatory LH surges and to maintain regular estrous cyclicity.

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