Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats

2007 ◽  
Vol 293 (5) ◽  
pp. E1325-E1334 ◽  
Author(s):  
Maristela O. Poletini ◽  
De'Nise T. McKee ◽  
Jessica E. Kennett ◽  
Jamie Doster ◽  
Marc E. Freeman
Keyword(s):  
Circadian Rhythm ◽  
Locus Coeruleus ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Random Sequence ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Gene Expressions ◽  
Circadian Time

The nature of the circadian signal from the suprachiasmatic nucleus (SCN) required for prolactin (PRL) surges is unknown. Because the SCN neuronal circadian rhythm is determined by a feedback loop of Period (Per) 1, Per2, and circadian locomotor output cycles kaput ( Clock) gene expressions, we investigated the effect of SCN rhythmicity on PRL surges by disrupting this loop. Because lesion of the locus coeruleus (LC) abolishes PRL surges and these neurons receive SCN projections, we investigated the role of SCN rhythmicity in the LC neuronal circadian rhythm as a possible component of the circadian mechanism regulating PRL surges. Cycling rats on proestrous day and estradiol-treated ovariectomized rats received injections of antisense or random-sequence deoxyoligonucleotide cocktails for clock genes ( Per1, Per2, and Clock) in the SCN, and blood samples were taken for PRL measurements. The percentage of tyrosine hydroxylase-positive neurons immunoreactive to Fos-related antigen (FRA) was determined in ovariectomized rats submitted to the cocktail injections and in a 12:12-h light:dark (LD) or constant dark (DD) environment. The antisense cocktail abolished both the proestrous and the estradiol-induced PRL surges observed in the afternoon and the increase of FRA expression in the LC neurons at Zeitgeber time 14 in LD and at circadian time 14 in DD. Because SCN afferents and efferents were probably preserved, the SCN rhythmicity is essential for the magnitude of daily PRL surges in female rats as well as for LC neuronal circadian rhythm. SCN neurons therefore determine PRL secretory surges, possibly by modulating LC circadian neuronal activity.

scholarly journals The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 323-335 ◽  
Author(s):  
Bruna Kalil ◽  
Aline B. Ribeiro ◽  
Cristiane M. Leite ◽  
Ernane T. Uchôa ◽  
Ruither O. Carolino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Median Eminence ◽  
Preoptic Area ◽  
Clock Genes ◽  
Third Ventricle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lh Surge ◽  
Clock Gene Expression

Abstract In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) of the preoptic area are considered to provide a major stimulatory input to the GnRH neuronal network that is responsible for triggering the preovulatory LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release, and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an α1-adrenergic receptor antagonist. In control rats, the estradiol-induced LH surge at 17 hours was associated with a significant increase in GnRH and kisspeptin content in the median eminence with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3 hours prior to the predicted time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the median eminence. In the preoptic area, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in the expression of the clock genes, Per1 and Bmal1. Together these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of α1-adrenergic receptors prior to the initiation of the LH surge and indicate a potential role of α1-adrenergic signaling in the circadian-controlled pathway timing of the preovulatory LH surge.

Effect of somatostatin on circadian rhythms of firing and 2-deoxyglucose uptake in rat suprachiasmatic slices

1993 ◽  
Vol 265 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
T. Hamada ◽  
S. Shibata ◽  
A. Tsuneyoshi ◽  
K. Tominaga ◽  
S. Watanabe
Keyword(s):  
Circadian Rhythm ◽  
Vasoactive Intestinal Polypeptide ◽  
Phase Changes ◽  
Circadian Clocks ◽  
Constant Darkness ◽  
Phase Resetting ◽  
Firing Activity ◽  
Light Pulses ◽  
Circadian Time

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus appears to act as a circadian clock. The SCN vasoactive intestinal polypeptide-like immunoreactive neurons, which may act to mediate photic information in the SCN, receive input from neurons immunoreactive for somatostatin (SST). Therefore we investigated the role of SST as a transmitter for entrainment by analyzing the phase-resetting effect of SST on the circadian rhythm of SCN firing activity. Perfusion of SST increased 2-deoxyglucose uptake at circadian time (CT) 18, but not at CT6. A 1-h or 15-min treatment with SST produced phase delays when it was administered at CT13-14 and phase advances at CT22-23. Thus SST-induced phase changes are similar to those for light pulses to animals under constant darkness. The present findings suggest that SST is a transmitter for mediating information of entrainment to circadian clocks within the SCN.

scholarly journals Vasopressinergic Activity of the Suprachiasmatic Nucleus and mRNA Expression of Clock Genes in the Hypothalamus-Pituitary-Gonadal Axis in Female Aging

2021 ◽  
Vol 12 ◽  
Author(s):  
Angela Cristina Nicola ◽  
Larissa Brazoloto Ferreira ◽  
Milene Mantovani Mata ◽  
Tatiane Vilhena-Franco ◽  
Cristiane Mota Leite ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Feedback Loops ◽  
Female Rats ◽  
Hpg Axis ◽  
Physiological Processes ◽  
Reproductive Axis ◽  
Reproductive Events ◽  
Vasopressinergic Neurons

The important involvement of the suprachiasmatic nucleus (SCN) and the activity of vasopressinergic neurons in maintaining the rhythmicity of the female reproductive system depends on the mRNA transcription-translation feedback loops. Therefore, circadian clock function, like most physiological processes, is involved in the events that determine reproductive aging. This study describes the change of mRNA expression of clock genes, Per2, Bmal1, and Rev-erbα, in the hypothalamus-pituitary-gonadal axis (HPG) of female rats with regular cycle (RC) and irregular cycle (IC), and the vasopressinergic neurons activity in the SCN and kisspeptin neurons in the arcuate nucleus (ARC) of these animals. Results for gonadotropins and the cFos/AVP-ir neurons in the SCN of IC were higher, but kisspeptin-ir was minor. Change in the temporal synchrony of the clock system in the HPG axis, during the period prior to the cessation of ovulatory cycles, was identified. The analysis of mRNA for Per2, Bmal1, and Rev-erbα in the reproductive axis of adult female rodents shows that the regularity of the estrous cycle is guaranteed by alternation in the amount of expression of Bmal1 and Per2, and Rev-erbα and Bmal1 between light and dark phases, which ceases to occur and contributes to determining reproductive senescence. These results showed that the desynchronization between the central and peripheral circadian clocks contributes to the irregularity of reproductive events. We suggest that the feedback loops of clock genes on the HPG axis modulate the spontaneous transition from regular to irregular cycle and to acyclicity in female rodents.

scholarly journals Astrocytic Modulation of Neuronal Activity in the Suprachiasmatic Nucleus: Insights from Mathematical Modeling

2020 ◽  
Vol 35 (3) ◽  
pp. 287-301
Author(s):  
Natthapong Sueviriyapan ◽  
Chak Foon Tso ◽  
Erik D. Herzog ◽  
Michael A. Henson
Keyword(s):  
Circadian Rhythm ◽  
Suprachiasmatic Nucleus ◽  
Neuronal Activity ◽  
Clock Genes ◽  
Rhythmic Activity ◽  
Neuronal Population ◽  
Circadian Period ◽  
Circadian Oscillators ◽  
Bidirectional Interactions ◽  
The Impact

The suprachiasmatic nucleus (SCN) of the hypothalamus consists of a highly heterogeneous neuronal population networked together to allow precise and robust circadian timekeeping in mammals. While the critical importance of SCN neurons in regulating circadian rhythms has been extensively studied, the roles of SCN astrocytes in circadian system function are not well understood. Recent experiments have demonstrated that SCN astrocytes are circadian oscillators with the same functional clock genes as SCN neurons. Astrocytes generate rhythmic outputs that are thought to modulate neuronal activity through pre- and postsynaptic interactions. In this study, we developed an in silico multicellular model of the SCN clock to investigate the impact of astrocytes in modulating neuronal activity and affecting key clock properties such as circadian rhythmicity, period, and synchronization. The model predicted that astrocytes could alter the rhythmic activity of neurons via bidirectional interactions at tripartite synapses. Specifically, astrocyte-regulated extracellular glutamate was predicted to increase neuropeptide signaling from neurons. Consistent with experimental results, we found that astrocytes could increase the circadian period and enhance neural synchronization according to their endogenous circadian period. The impact of astrocytic modulation of circadian rhythm amplitude, period, and synchronization was predicted to be strongest when astrocytes had periods between 0 and 2 h longer than neurons. Increasing the number of neurons coupled to the astrocyte also increased its impact on period modulation and synchrony. These computational results suggest that signals that modulate astrocytic rhythms or signaling (e.g., as a function of season, age, or treatment) could cause disruptions in circadian rhythm or serve as putative therapeutic targets.

Modulatory role of locus coeruleus and estradiol on the stress response of female rats

Endocrine ◽  
2009 ◽  
Vol 35 (2) ◽  
pp. 166-176 ◽  
Author(s):  
Isac Alexandre Ferreira-Silva ◽  
Cleyde Vanessa Vega Helena ◽  
Celso Rodrigues Franci ◽  
Aldo Bolten Lucion ◽  
Janete Aparecida Anselmo-Franci
Keyword(s):  
Stress Response ◽  
Locus Coeruleus ◽  
Female Rats

scholarly journals Influence of sex, estrous cycle, and estrogen on intracranial dural mast cells

Cephalalgia ◽  
2012 ◽  
Vol 32 (12) ◽  
pp. 924-931 ◽  
Author(s):  
Tanner Boes ◽  
Dan Levy
Keyword(s):  
Mast Cells ◽  
Estrous Cycle ◽  
Potential Role ◽  
Ovarian Hormones ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Migraine Headaches ◽  
Male And Female Rats ◽  
Quantitative Analyses

Background: The frequency of migraine headaches is higher in women than in men and in susceptible women attacks are related to changes in ovarian hormone levels. Intracranial mast cells (MCs) are likely to have a role in migraine headache genesis, and changes in the dural MC population might influence headache susceptibility. The present study thus tested the hypothesis that sex and ovarian hormones influence the density and phenotypic makeup of dural MCs. Methods: Histochemistry combined with quantitative analyses was used to investigate sex differences, estrous cycle and ovarian hormones on dural MC density, phenotype and degranulation level in male and female rats. Results: Our data show that in female rats, dural MC density fluctuates during the estrous cycle and is overall higher than in males. In ovariectomized rats, estradiol, but not progesterone, promoted an increase in dural MC density. This effect was abolished by a splenectomy, suggesting estrogen-related recruitment of MCs from the spleen. Finally, our data suggest that the phenotypic make up of dural MCs, which represents the level of cellular maturity, is also governed by changes in estrogen levels. Conclusions: Given the potential role of dural MCs in triggering headache, our data suggest that estrogen-related modulation of dural MC density and phenotypic makeup could have a role in mediating the higher frequency and severity of headaches such as migraine, in women.

scholarly journals Minireview: Timely Ovulation: Circadian Regulation of the Female Hypothalamo-Pituitary-Gonadal Axis

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1148-1153 ◽  
Author(s):  
Horacio O. de la Iglesia ◽  
William J. Schwartz
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Clock Genes ◽  
Female Rats ◽  
Circadian Regulation ◽  
Pituitary Cells ◽  
Neural Oscillators ◽  
Lh Surge ◽  
Pharmacological Data ◽  
Circadian Clock Genes ◽  
Estradiol Levels

The preovulatory surge in the secretion of LH is timed by a neuroendocrine integrative mechanism that involves ovarian estradiol levels and the endogenous circadian system. Studies in female rats and hamsters have established that the clock in the hypothalamic suprachiasmatic nucleus has a preeminent role in setting the LH surge, and anatomical, physiological, and pharmacological data are revealing the responsible connections between suprachiasmatic nucleus neurons and GnRH and estradiol-receptive areas. Recent investigations show that GnRH and pituitary cells express circadian clock genes that might play a role in the release and reception of the GnRH signal. Analysis of the circadian regulation of the LH surge may provide a model for understanding how multiple neural oscillators function within other neuroendocrine axes.

Increased heat loss in ovariectomized hypothyroid rats treated with estradiol

1982 ◽  
Vol 243 (1) ◽  
pp. R70-R76
Author(s):  
M. L. Laudenslager ◽  
H. J. Carlisle ◽  
S. E. Calvano
Keyword(s):  
Heat Loss ◽  
Heat Production ◽  
Cold Exposure ◽  
Thermal Balance ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Absolute Rate ◽  
Intact Female ◽  
Dry Heat

The role of the thyroid in the mediation of an estrogen-associated change in thermal balance was studied in thyroidectomized and in propylthiouracil-treated ovariectomized rats. Prior to propylthiouracil treatment, estrogen-treated ovariectomized rats and intact female rats had higher rates of heat production and dry heat loss at -5 degrees C than ovariectomized rats. Heat production of estrogen-treated and intact female rats was well below their rates of dry heat loss without an alteration in the absolute rate of heat loss in the hypothyroid condition. Heat production exceeded heat loss only in the hypothyroid ovariectomized group not receiving estrogen. Ovariectomized rats without estrogen maintained thermal balance, whereas rectal temperatures fell in both intact and estrogen-treated ovariectomized rats during cold exposure. Increased heat loss unbalanced by heat production was also observed in surgically thyroidectomized estrogen-treated ovariectomized rats tested at -5 degrees C. These results suggest that an estrogen-induced increase in heat loss, which is compensated by an increase in heat production in the euthyroid but not the hypothyroid condition, is one mechanism responsible for estrogen-associated changes in thermal balance during cold exposure.

Role of the subcommissural organ in the control of gonadotrophin secretion in the female rat

1982 ◽  
Vol 95 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Patrizia Limonta ◽  
Roberto Maggi ◽  
Luciano Martini ◽  
Flavio Piva
Keyword(s):  
Subcommissural Organ ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Normal Female ◽  
Female Rat ◽  
Thermal Lesions ◽  
Gonadotrophin Secretion

Thermal lesions were placed in the subcommissural organ (SCO) of female rats with normal cycles and long-term ovariectomized rats. In normal female rats SCO lesions disrupted the oestrous cycle in more than half of the animals, the majority of which entered a state of prolonged dioestrus. In these animals, serum gonadotrophin levels were similar to those of rats with regular cycles on day 2 of dioestrus. In animals in which the oestrous cycle was maintained, a delayed LH surge occurred on the day of pro-oestrus and the pro-oestrous FSH surge was absent. The usual increase in FSH on the day of oestrus was present. Lesions in the SCO did not change the high gonadotrophin levels typical of ovariectomized animals. These results suggested that the SCO may play a role in the control of the cyclic but not the tonic release of the gonadotrophins. In particular, it appears that the SCO might be involved in the regulation of the hypersecretion of FSH during the day of pro-oestrus.

scholarly journals Temporal expression of estrogen receptor α in the hypothalamus and medulla oblongata during fasting: a role of noradrenergic neurons

2006 ◽  
Vol 190 (3) ◽  
pp. 593-600 ◽  
Author(s):  
Beverly A S Reyes ◽  
Hiroko Tsukamura ◽  
Helen I’Anson ◽  
Maria Amelita C Estacio ◽  
Kanjun Hirunagi ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Brain Regions ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Noradrenergic Neurons ◽  
Anatomical Relationship ◽  
Relationship Of ◽  
Lh Secretion

Fasting-induced LH suppression is augmented by estrogen in female rats. We investigated the temporal changes in the number of estrogen receptor α (ERα)-immunoreactive (ir) cells in various brain regions in ovariectomized rats fasted for 6, 24, 30, and 48 h, commencing at 1300 h. We also determined the anatomical relationship of ERα immunoreactivity and dopamine-β-hydroxylase (DBH) neurons in the A2 region of the nucleus of the solitary tract (NTS) and the paraventricular nucleus (PVN). The number of ERα-ir cells significantly increased after 30 h from the onset of fasting in the PVN and NTS compared with the unfasted controls and was sustained until 48 h. In the A2 region of 48-h fasted rats, 46.75% DBH-ir cells expressed ERα, and this was significantly higher than in unfasted controls (8.16% DBH-ir cells expressed ERα). In the PVN, most ERα-ir neurons were juxtaposed with DBH-ir varicosities. These results suggest that ERα is expressed in specific brain regions at a defined time from the onset of fasting. In addition, the anatomical relationship of noradrenergic and ERα-ir neurons in the A2 region and PVN may suggest a role for estrogen in increasing the activity of noradrenergic neurons in the A2 region and enhancing sensitivity of the PVN to noradrenergic input arising from the lower brainstem and thereby augmenting the suppression of LH secretion during fasting.

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