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Frontiers in Physiology 2024Molecular and physiological determinants of the timing of reproductive events, including the pre-ovulatory LH surge and seasonal fluctuations in fertility, are...
Molecular and physiological determinants of the timing of reproductive events, including the pre-ovulatory LH surge and seasonal fluctuations in fertility, are incompletely understood. We used the -deficient duper mutant to examine the role of this core circadian clock gene in Syrian hamsters. We find that the phase of the LH surge and its stability upon shifts of the light: dark cycle are altered in duper mutants. The intensity of immunoreactive PER1 in GnRH cells of the preoptic area peaks earlier in the day in duper than wild type hamsters. We note that GnRH fibers coursing through the suprachiasmatic nucleus (SCN) contact vasopressin- and VIP-immunoreactive cells, suggesting a possible locus of circadian control of the LH surge. Unlike wild types, duper hamsters do not regress their gonads within 8 weeks of constant darkness, despite evidence of melatonin secretion during the subjective night. In light of the finding that the duper allele is a stop codon in , our results suggest important neuroendocrine functions of this core circadian clock gene.
PubMed: 38444761
DOI: 10.3389/fphys.2024.1351682 -
The Journal of Physiological Sciences :... Mar 2024Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits... (Review)
Review
Intraocular pressure (IOP) plays a crucial role in glaucoma development, involving the dynamics of aqueous humor (AH). AH flows in from the ciliary body and exits through the trabecular meshwork (TM). IOP follows a circadian rhythm synchronized with the suprachiasmatic nucleus (SCN), the circadian pacemaker. The SCN resets peripheral clocks through sympathetic nerves or adrenal glucocorticoids (GCs). IOP's circadian rhythm is governed by circadian time signals, sympathetic noradrenaline (NE), and GCs, rather than the local clock. The activity of Na/K-ATPase in non-pigmented epithelial cells in the ciliary body can influence the nocturnal increase in IOP by enhancing AH inflow. Conversely, NE, not GCs, can regulate the IOP rhythm by suppressing TM macrophage phagocytosis and AH outflow. The activation of the β1-adrenergic receptor (AR)-mediated EPAC-SHIP1 signal through the ablation of phosphatidylinositol triphosphate may govern phagocytic cup formation. These findings could offer insights for better glaucoma management, such as chronotherapy.
Topics: Humans; Intraocular Pressure; Glaucoma; Trabecular Meshwork; Aqueous Humor; Circadian Rhythm; Glucocorticoids
PubMed: 38431563
DOI: 10.1186/s12576-024-00905-8 -
Drug Delivery and Translational Research Jul 2024Circadian rhythms influence a range of biological processes within the body, with the central clock or suprachiasmatic nucleus (SCN) in the brain synchronising... (Review)
Review
Circadian rhythms influence a range of biological processes within the body, with the central clock or suprachiasmatic nucleus (SCN) in the brain synchronising peripheral clocks around the body. These clocks are regulated by external cues, the most influential being the light/dark cycle, in order to synchronise with the external day. Chrono-tailored or circadian drug delivery systems (DDS) aim to optimise drug delivery by releasing drugs at specific times of day to align with circadian rhythms within the body. Although this approach is still relatively new, it has the potential to enhance drug efficacy, minimise side effects, and improve patient compliance. Chrono-tailored DDS have been explored and implemented in various conditions, including asthma, hypertension, and cancer. This review aims to introduce the biology of circadian rhythms and provide an overview of the current research on chrono-tailored DDS, with a particular focus on immunological applications and vaccination. Finally, we draw on some of the key challenges which need to be overcome for chrono-tailored DDS before they can be translated to more widespread use in clinical practice.
Topics: Humans; Drug Delivery Systems; Circadian Rhythm; Animals; Drug Chronotherapy
PubMed: 38416386
DOI: 10.1007/s13346-024-01539-4 -
Cephalalgia : An International Journal... Feb 2024Despite advances in neuroimaging and electrophysiology, cluster headache's pathogenesis remains unclear. This review will examine clinical neurophysiology studies,... (Review)
Review
BACKGROUND
Despite advances in neuroimaging and electrophysiology, cluster headache's pathogenesis remains unclear. This review will examine clinical neurophysiology studies, including electrophysiological and functional neuroimaging, to determine if they might help us construct a neurophysiological model of cluster headache.
RESULTS
Clinical, biochemical, and electrophysiological research have implicated the trigeminal-parasympathetic system in cluster headache pain generation, although the order in which these two systems are activated, which may be somewhat independent, is unknown. Electrophysiology and neuroimaging have found one or more central factors that may cause seasonal and circadian attacks. The well-known posterior hypothalamus, with its primary circadian pacemaker suprachiasmatic nucleus, the brainstem monoaminergic systems, the midbrain, with an emphasis on the dopaminergic system, especially when cluster headache is chronic, and the descending pain control systems appear to be involved. Functional connection investigations have verified electrophysiological evidence of functional changes in distant brain regions connecting to wide cerebral networks other than pain.
CONCLUSION
We propose that under the impact of external time, an inherited misalignment between the primary circadian pacemaker suprachiasmatic nucleus and other secondary extra- suprachiasmatic nucleus clocks may promote disturbance of the body's internal physiological clock, lowering the threshold for bout recurrence.
Topics: Humans; Cluster Headache; Suprachiasmatic Nucleus; Pain; Brain; Brain Stem
PubMed: 38415635
DOI: 10.1177/03331024231209317 -
Animals : An Open Access Journal From... Feb 2024Melatonin is a hormone mainly produced by the pineal gland in the absence of light stimuli. The light, in fact, hits the retina, which sends a signal to the... (Review)
Review
Melatonin is a hormone mainly produced by the pineal gland in the absence of light stimuli. The light, in fact, hits the retina, which sends a signal to the suprachiasmatic nucleus, which inhibits the synthesis of the hormone by the epiphysis. Mostly by interacting with MT1/MT2 membrane receptors, melatonin performs various physiological actions, among which are its regulation of the sleep-wake cycle and its control of the immune system. One of its best known functions is its non-enzymatic antioxidant action, which is independent from binding with receptors and occurs by electron donation. The hormone is also an indicator of the photoperiod in seasonally reproducing mammals, which are divided into long-day and short-day breeders according to the time of year in which they are sexually active and fertile. It is known that melatonin acts at the hypothalamic-pituitary-gonadal axis level in many species. In particular, it inhibits the hypothalamic release of GnRH, with a consequent alteration of FSH and LH levels. The present paper mainly aims to review the ovarian effect of melatonin.
PubMed: 38396612
DOI: 10.3390/ani14040644 -
IScience Mar 2024The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal...
The hypothalamic suprachiasmatic nucleus (SCN) is composed of heterogenous populations of neurons that express signaling peptides such as vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP) and regulate circadian rhythms in behavior and physiology. SCN neurons acquire functional and morphological specializations from waves of transcription factors (TFs) that are expressed during neurogenesis. However, the generation of SCN neurons has never been achieved. Here we supplemented a highly efficient neuronal conversion protocol with TFs that are expressed during SCN neurogenesis, namely , , , and . Neurons induced from mouse and human fibroblasts predominantly exhibited neuronal properties such as bipolar or multipolar morphologies, GABAergic neurons with expression of VIP. Our study reveals a critical contribution of these TFs to the development of vasoactive intestinal peptide (Vip) expressing neurons in the SCN, suggesting the regenerative potential of neuronal subtypes contained in the SCN for future SCN regeneration and disease remodeling.
PubMed: 38384840
DOI: 10.1016/j.isci.2024.109051 -
CNS Neuroscience & Therapeutics Feb 2024Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and...
AIMS
Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear.
METHOD
Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity.
RESULTS
In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side.
CONCLUSION
Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery.
Topics: Humans; Male; Rats; Animals; Zolpidem; Pyridines; Stroke; Sleep Wake Disorders; Infarction, Middle Cerebral Artery; Sleep; Ischemic Stroke
PubMed: 38380702
DOI: 10.1111/cns.14637 -
Journal of Biological Rhythms Apr 2024It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments... (Review)
Review
It has been 50 years since the suprachiasmatic nucleus (SCN) was first identified as the central circadian clock and 25 years since the last overview of developments in the field was published in the . Here, we explore new mechanisms and concepts that have emerged in the subsequent 25 years. Since 1997, methodological developments, such as luminescent and fluorescent reporter techniques, have revealed intricate relationships between cellular and network-level mechanisms. In particular, specific neuropeptides such as arginine vasopressin, vasoactive intestinal peptide, and gastrin-releasing peptide have been identified as key players in the synchronization of cellular circadian rhythms within the SCN. The discovery of multiple oscillators governing behavioral and physiological rhythms has significantly advanced our understanding of the circadian clock. The interaction between neurons and glial cells has been found to play a crucial role in regulating these circadian rhythms within the SCN. Furthermore, the properties of the SCN network vary across ontogenetic stages. The application of cell type-specific genetic manipulations has revealed components of the functional input-output system of the SCN and their correlation with physiological functions. This review concludes with the high-risk effort of identifying open questions and challenges that lie ahead.
Topics: Circadian Rhythm; Neuropeptides; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Gastrin-Releasing Peptide
PubMed: 38366616
DOI: 10.1177/07487304231225706 -
Naunyn-Schmiedeberg's Archives of... Feb 2024Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now... (Review)
Review
Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time.
PubMed: 38358468
DOI: 10.1007/s00210-024-02972-5 -
Psychoneuroendocrinology May 2024Perinatal testosterone, or its metabolite estradiol, organize the brain toward a male phenotype. Male rodents with insufficient testosterone during this period fail to...
Cohabitation with receptive females under D2-type agonism in adulthood restores partner preference and brain dimorphism in the SDN-POA following neonatal gonadectomy in male rats.
Perinatal testosterone, or its metabolite estradiol, organize the brain toward a male phenotype. Male rodents with insufficient testosterone during this period fail to display sexual behavior and partner preference for receptive females in adulthood. However, cohabitation with non-reproductive conspecifics under the influence of a D2 agonist facilitates the expression of conditioned partner preference via Pavlovian learning in gonadally intact male rats. In the present experiment, three groups of neonatal PD1 males (N = 12/group) were either gonadectomized (GDX), sham-GDX, or left intact and evaluated for social preferences and sexual behaviors as adults. We then examined whether the effects of GDX could be reversed by conditioning the males via cohabitation with receptive females under the effects of the D2 agonist quinpirole (QNP) or saline, along with the size of some brain regions, such as the sexually dimorphic nucleus of the preoptic area (SDN-POA), suprachiasmatic nucleus (SCN), posterior dorsal medial amygdala (MeApd) and ventromedial hypothalamus (VMH). Results indicated that neonatal GDX resulted in the elimination of male-typical sexual behavior, an increase in same-sex social preference, and a reduction of the area of the SDN-POA. However, GDX-QNP males that underwent exposure to receptive females in adulthood increased their social preference for females and recovered the size in the SDN-POA. Although neonatal GDX impairs sexual behavior and disrupts partner preference and brain dimorphism in adult male rats, Pavlovian conditioning under enhanced D2 agonism ameliorates the effects on social preference and restores brain dimorphism in the SDN-POA without testosterone.
Topics: Pregnancy; Rats; Animals; Male; Female; Preoptic Area; Sex Characteristics; Brain; Quinpirole; Castration; Testosterone
PubMed: 38342055
DOI: 10.1016/j.psyneuen.2024.106988