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Biomedical subjects

S M Reppert

Publications and source records attributed to S M Reppert.

At least 109 records · Page 6Linked to original sources
PubMed1988

Anatomic and functional development of the suprachiasmatic nuclei in the gray short-tailed opossum.

The anatomic and functional development of the suprachiasmatic nuclei (SCN) was studied in the gray short-tailed opossum, Monodelphis domestica. To provide a background for developmental studies, daily patterns of wheel-running behavior and SCN metabolic activity were studied in adult animals. Adult opossums manifested robust circadian rhythms in locomotor activity that were entrained by the daily light-dark cycle. The temporal course of SCN metabolic activity, studied by the 14C-labeled deoxyglucose autoradiographic technique, showed that the adult SCN were metabolically active throughout subjective day and relatively inactive during subjective night. SCN neurogenesis, determined using 3H-thymidine autoradiography, was active at postnatal day 3, the earliest age studied, and continued until postnatal day 7. It was not until postnatal day 16 that the SCN appeared as distinct nuclei by light microscopy. Study of the ontogeny of the daily rhythm in SCN metabolic activity showed that the nuclei were metabolically active during both day and night at postnatal day 16. On day 20, a clear day-night rhythm in SCN metabolic activity was first observed; the rhythm was even more pronounced on day 27. These results indicate that the gray short-tailed opossum has a functioning circadian timing system and that the anatomic and functional development of the SCN in this species occurs during the postnatal period.

Animals↗
PubMed1987

The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain.

The roles of the maternal suprachiasmatic nuclei (SCN) and fetal brain in the circadian-gated timing of birth were studied in rats. The circadian gating of birth was shown by exposing different groups of dams to lighting cycles of opposite phase during pregnancy. Regardless of the phase of the prenatal lighting cycle, the time of birth was gated over a 36-h temporal window so that most births occurred during subjective day. Destruction of the maternal SCN eliminated the circadian gating; births occurred in a single distribution that peaked in the middle of the 36-h window. Removal of the fetal brain also disrupted the circadian gating of birth; dams of brain-aspirated fetuses no longer exhibited a daytime preference for births. These results show that the maternal SCN are necessary for the normal circadian gating of birth and are also consistent with a role for the fetal brain in this process.

Age Factors↗
PubMed1987

The hypothalamic suprachiasmatic nuclei: circadian patterns of vasopressin secretion and neuronal activity in vitro.

The suprachiasmatic nuclei (SCN) are intrinsic pacemakers which organize circadian rhythms in mammals. When the SCN of Long-Evans rats are surgically isolated and perifused in vitro, they retain the ability to express a 24 hr rhythm of neuronal firing rate. We find that the SCN are also capable of secreting the peptide vasopressin (VP) in a circadian pattern. The pattern of VP secretion is similar to that of SCN neuronal electrical activity measured during perfusate collection. The temporal profile of VP levels in SCN perfusate parallels that seen in cerebrospinal fluid, suggesting that the SCN might be both the pacemaker and a secretory contributor to this rhythm.

Action Potentials↗
PubMed1987

Maternal-fetal communication of circadian phase in a precocious rodent, the spiny mouse.

The development of circadian rhythms was examined in a precocious rodent species, the spiny mouse. Spiny mouse pups born and reared in constant darkness expressed robust circadian rhythms in locomotor activity as early as day 5 of life. Free-running activity rhythms of pups born and reared in constant darkness were coordinated with the dam on the day of birth. Postnatal maternal influences on pup rhythmicity are minimal in this species, as pups fostered on the day of birth to dams whose circadian phases were opposite to the pups' original dams were coordinated with their original dams on the day of birth. Studies using 2-deoxy-D-[1-14C]-glucose autoradiography showed that there were synchronous (coordinated) rhythms in metabolic activity in the maternal and fetal suprachiasmatic nuclei, directly demonstrating prenatal coordination of maternal and fetal rhythmicity. Maternal-fetal coordination of circadian phase was not the result of direct entrainment of the fetuses to the environmental light-dark cycle. These results demonstrate that there is prenatal communication of circadian phase in this precocious species, without demonstrable postnatal maternal influences on pup circadian rhythmicity. Spiny mice therefore represent an important animal model in which circadian rhythms in the postnatal period can be used to precisely assess prenatal influences on circadian phase.

Animals↗
PubMed1987

Definition of a prenatal sensitive period for maternal-fetal communication of day length.

The duration of the nocturnal elevation of melatonin in the dam is a key feature in providing the Djungarian hamster fetus with a prenatal photoperiodic history. The developing animal compares the prenatal photoperiod with the photoperiod experienced during the postnatal period to properly time puberty. In the present report, we define the period during gestation when melatonin administered to the dam is effective in providing the fetus with a prenatal photoperiodic history. The administration of melatonin (50 ng delivered over 10 h at night) by timed infusions to pregnant, pinealectomized Djungarian hamsters for the last 4-7 days of gestation stimulated testicular weights of male pups reared in 14 h of light/day. Single 10-h melatonin infusions were ineffective in stimulating reproductive development (testes weights on day 34) of the male pups, irrespective of the gestational age of the fetus at the time of treatment. In contrast, two consecutive nightly 10-h infusions during gestation clearly stimulated testicular development. The gestational age of the fetus at the time of infusion strongly influenced the response, however. Treatments beginning between 6 and 3 days before birth were effective in stimulating postnatal reproductive development of the offspring. These results indicate that there is a well-delineated, sensitive period during prenatal development when melatonin can provide the fetus with a prenatal photoperiodic history.

Age Factors↗
PubMed1987

Vasopressin messenger ribonucleic acid in supraoptic and suprachiasmatic nuclei: appearance and circadian regulation during development.

The developmental appearance and regulation of hypothalamic vasopressin (prepropressophysin) mRNA was studied using quantitated in situ hybridization techniques. Vasopressin mRNA levels in the supraoptic nuclei were reliably detected on day 16 of gestation, while mRNA in the suprachiasmatic nuclei (SCN) was detectable on day 21. These developmental patterns correlate well with the immunohistochemical appearance of prepropressophysin translation products previously reported in these nuclei. A prominent day-night rhythm of vasopressin mRNA levels was evident in the SCN on day 21 of gestation; the rhythm was also present on postnatal days 2 and 11. No such rhythm was present in the supraoptic nuclei at any developmental stage examined. These results demonstrate regulated expression of the vasopressin gene during fetal life. Vasopressin mRNA levels in the SCN are already under specific circadian control when the nuclei are morphologically immature and lacking many of the connections found in adult animals.

Animals↗
PubMed1986

Suprachiasmatic nucleus vasopressin messenger RNA: circadian variation in normal and Brattleboro rats.

In situ hybridization of an oligonucleotide probe complementary to vasopressin messenger RNA (mRNA) in sections from normal or Brattleboro rat hypothalami revealed hybridization densities in each of three vasopressin-rich nuclei: the supraoptic, paraventricular, and suprachiasmatic. When entrained to a daily light-dark cycle, each rat strain displayed diurnal variation in hybridizable mRNA in the suprachiasmatic, but not in the supraoptic or paraventricular nuclei. The higher values for suprachiasmatic mRNA in the morning correlate well with previously elucidated morning increases in vasopressin immunoreactivity in the cerebrospinal fluid. These results support the utility of in situ hybridization techniques for elucidating physiological influences on regional peptidergic function, are consistent with a prominent role for vasopressinergic suprachiasmatic neurons in generating the cerebrospinal fluid vasopressin rhythm, and suggest that regulation of this mRNA rhythm is not dependent on release of intact peptide.

Animals↗
PubMed1986

Developmental appearance of light-dark entrainment in the rat.

Previous studies show that the developing circadian system is entrained by a maternal signal during the prenatal and early postnatal period. The present study investigated the developmental onset of retina-mediated, light-dark entrainment. Juvenile rats were exposed to phase-shifts in the light-dark cycle at different ages and the pineal N-acetyltransferase rhythm was monitored on postnatal day 10. The results show that retina-mediated, light-dark entrainment begins by postnatal day 6 and overrides maternal entrainment by postnatal day 8.

Acetyltransferases↗
PubMed1986

Maternal endocrine extirpations do not abolish maternal coordination of the fetal circadian clock.

The maternal circadian system coordinates the timing of the fetal circadian clock to the prevailing light-dark cycle. The role of various maternal endocrine organs as the source of a coordinating signal was investigated in rats. Either metabolic activity of the fetal suprachiasmatic nuclei or pineal N-acetyltransferase activity in 10-day-old pups was used to monitor the fetal circadian clock. Extirpations of the maternal pituitary, adrenals, thyroid-parathyroids, ovaries, or pineal (each performed in separate experiments) did not abolish maternal coordination.

Acetyltransferases↗
PubMed1986

Maternal melatonin communicates daylength to the fetus in Djungarian hamsters.

Daylength (photoperiod) influences the rate of reproductive development in the juveniles of some photoperiodic species. Recent studies show that daylength during the prenatal period is perceived by the fetus and that this perception can profoundly influence postnatal reproductive and somatic development. Using the photoperiodic Djungarian hamster, we assessed the role of the maternal pineal gland and its hormone, melatonin, in this prenatal perception of daylength. Maternal pinealectomy eliminated the influence of prenatal photoperiod on testicular and body weights of male pups, suggesting that a product from the maternal pineal gland communicates daylength to the fetus. Infusion of the pineal hormone melatonin into pinealectomized dams for various durations during gestation mimicked the effect of varying the prenatal photoperiod on both testicular and body weights. These results indicate that pineal melatonin is involved in this novel form of communication from mother to fetus.

Animals↗
PubMed1986

Maternal suprachiasmatic nuclei are necessary for maternal coordination of the developing circadian system.

During late fetal and early neonatal life, the maternal circadian system coordinates the timing of a circadian clock in the hypothalamic suprachiasmatic nuclei (SCN) to the prevailing light-dark cycle. The role of the maternal SCN in the process of maternal coordination was investigated in rats. Complete lesions of the maternal SCN on day 7 of gestation disrupted rhythms of SCN glucose utilization in fetuses and pineal N-acetyltransferase activity in 10-d-old pups. This disruption was probably due to the desynchronization of individually oscillating fetal SCN, because individual pups born to and reared by SCN-lesioned dams under constant conditions exhibited normal circadian rhythms in drinking behavior. Cross-foster studies showed that the maternal circadian system can coordinate developing circadian rhythmicity during either the pre- or postnatal period. The results indicate that the maternal SCN are a necessary component of the mechanism of maternal coordination during both the pre- and postnatal periods.

Acetyltransferases↗
PubMed1985

Photic influences on the developing mammal.

In adult mammals, the daily light-dark cycle acts via the retinohypothalamic pathway to entrain the circadian clock in the suprachiasmatic nuclei (SCN) and to communicate information about daylength to photoperiodic species. Studies in rats show that during late fetal and early neonatal life, before the retinohypothalamic pathway has innervated the SCN, the maternal circadian system entrains the timing of the developing clock to prevailing lighting conditions. Although the nature of the maternal output signal(s) used to entrain the developing clock has not been elucidated, the maternal SCN are a necessary component of maternal entrainment during both prenatal and postnatal life. Maternal entrainment of the fetal and neonatal clock thus ensures that the developing circadian system is synchronized to the outside world until maturation of the retinohypothalamic pathway permits direct photic entrainment. The maternal circadian system is not only necessary for entrainment of the developing circadian system, but recent studies suggest it may also provide the immature mammal with important photoperiodic information. In the montane vole (Microtus montanus) and the Djungarian hamster (Phodopus sungorus), the prenatal photoperiod affects postnatal photoperiodic responses, and cross-fostering experiments show that this information about daylength is perceived by the fetus. This prenatal information, in conjunction with postnatal perception of photoperiod, allows the developing animal to determine which way the season is changing and to modify the rate of reproductive maturation accordingly.

Aging↗
PubMed1985

CSF vasopressin rhythm is effectively insulated from osmotic regulation of plasma vasopressin.

By using our method for continuous removal of cisternal cerebrospinal fluid (CSF) and intermittent sampling of blood from unanesthetized freely moving cats, we investigated the effect of osmotic-induced changes in plasma vasopressin on the daily rhythm of CSF vasopressin. Examination of the daily profiles of vasopressin and osmolality in the CSF and plasma of six euhydrated animals showed that CSF vasopressin concentrations exhibit a clear daily rhythm, whereas CSF osmolality and plasma vasopressin and osmolality do not exhibit such daily variation. A 48-h period of water deprivation caused marked sustained elevations in plasma vasopressin concentrations, which returned to basal levels on rehydration. In contrast, water deprivation had only a small effect on the CSF vasopressin rhythm. Although there was a significant elevation of the normally low nighttime CSF vasopressin levels during water deprivation in three of the four animals studied, high daytime vasopressin levels were unaltered and the daily rhythm was clearly evident before, during, and after the period of water removal in all animals. Changes between plasma vasopressin and osmolality were significantly correlated in all animals. Changes between plasma and CSF osmolality were significantly correlated in three of the four animals. The data indicate that the circadian regulation of the CSF vasopressin rhythm is effectively insulated from the osmotic regulation of plasma vasopressin.

Animals↗
PubMed1985

Hormonal responses to short term fasting in postmenopausal women.

Urinary excretion of gonadotropins increases during fasting. We investigated whether this increase results from increased pituitary secretion of LH and FSH or from altered renal excretion of protein molecules. To this end, we studied urinary gonadotropin excretion, serum gonadotropin levels, and pituitary responsiveness of LHRH during control, 10-day fasting, and refeeding periods in 10 mildly obese postmenopausal women. Additionally, we measured urinary cortisol and estriol excretion and circulating levels of dehydroepiandrosterone sulfate, estradiol, estrone, melatonin, norepinephrine, epinephrine, and dopamine during the control, fasting, and refeeding periods. While urinary excretion of gonadotropins increased markedly during fasting, there were no significant changes in serum gonadotropin levels or in the pituitary sensitivity to LHRH. Plasma norepinephrine and serum melatonin increased significantly during fasting, but serum and urinary estrogens, indices of adrenal activity, and plasma levels of epinephrine and dopamine did not change. These results show that the stress of short term fasting selectively activates only certain components of the neuroendocrine system without any appreciable changes in the function of the gonadotropin-secreting system. Fasting-induced gonadotropinuria is probably explained by altered renal handling of gonadotropin molecules.

Adult↗
PubMed1985

Neural regulation of the circadian vasopressin rhythm in cerebrospinal fluid: a pre-eminent role for the suprachiasmatic nuclei.

The neuroanatomical system responsible for the generation and expression of the circadian vasopressin rhythm in cerebrospinal fluid (CSF) is investigated. CSF was serially withdrawn in individual, unanesthetized, unrestrained rats after neuroendocrine extirpations or stereotaxic brain lesions were made; the peptide was assayed using a sensitive and specific radioimmunoassay. Hypophysectomy or pinealectomy did not eliminate vasopressin from CSF; both day and night-time peptide levels in hypophysectomized rats were elevated above control levels. Complete lesions of the suprachiasmatic nuclei (SCN) abolished both the rhythm and in most cases the measurable level of peptide in CSF. Neither lesions of the paraventricular nuclei nor hypothalamic knife cuts interrupting most neural efferents from the SCN had this effect; in these cases, vasopressin rhythms persisted with diminished amplitude. Our results suggest that the circadian CSF vasopressin rhythm is produced by a neural system topographically separate from the classical magnocellular hypothalamo-neurohypophyseal system for the secretion of peptide into blood. The SCN are an important component of this new system and are necessary for the generation of the CSF rhythm.

Animals↗
PubMed1984

The circadian rhythm of oxytocin in primate cerebrospinal fluid: effects of destruction of the suprachiasmatic nuclei.

The effects of lesions of the suprachiasmatic nuclei (SCN) on the circadian rhythm of oxytocin concentrations in cerebrospinal fluid (CSF) were examined in the rhesus monkey. In the two sham-operated animals, the rhythm was normally entrained to the daily light-dark cycle and persisted in constant lighting conditions at both 4 and 8 months after surgery. Similarly, the oxytocin rhythm was clearly manifested in the two animals with complete SCN ablation 4 months after surgery. At 8 months after surgery, however, the daily CSF rhythm was disrupted in one of the lesioned animals, while it persisted in the other animal. The data show that the SCN are not required for the expression of the daily rhythm of CSF oxytocin, suggesting that a circadian system outside the SCN normally generates the oxytocin rhythm.

Animals↗