-
Frontiers in Neuroanatomy 2023The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and...
Ontogenetic changes in the tyrosine hydroxylase immunoreactive preoptic area in the small-spotted catshark (L., 1758) females: catecholaminergic involvement in sexual maturation.
INTRODUCTION
The catecholaminergic component of the brain-pituitary-gonadal axis, which mediates the influence of external and internal stimuli on the central nervous system and gonad development in vertebrates, is largely unexplored in Chondrichthyes. We considered (L., 1758) females as a model for this vertebrate's class, to assess the involvement of the catecholaminergic system of the brain in its reproduction. Along the reproductive cycle, we characterized and evaluated differences in somata morphometry and the number of putative catecholaminergic neurons in two brain nuclei: the periventricular preoptic nucleus, hypothesized to be a positive control for ovarian development, and the suprachiasmatic nucleus, examined as a negative control.
MATERIALS AND METHODS
16 wild females were sampled and grouped in maturity stages (immature, maturing, mature, and mature egg-laying). The ovary was histologically processed for the qualitative description of maturity stages. Anti-tyrosine hydroxylase immunofluorescence was performed on the diencephalic brain sections. The immunoreactive somata were investigated for morphometry and counted using the optical fractionator method, throughout the confocal microscopy.
RESULTS AND DISCUSSIONS
Qualitative and quantitative research confirmed two separate populations of immunoreactive neurons. The modifications detected in the preoptic nucleus revealed that somata were more numerous, significantly smaller in size, and more excitable during the maturing phase but decreased, becoming slightly bigger and less excitable in the egg-laying stage. This may indicate that the catecholaminergic preoptic nucleus is involved in the control of reproduction, regulating both the onset of puberty and the imminent spawning. In contrast, somata in the suprachiasmatic nucleus grew in size and underwent turnover in morphometry, increasing the total number from the immature-virgin to maturing stage, with similar values in the more advanced maturity stages. These changes were not linked to a reproductive role. These findings provide new valuable information on Chondrichthyes, suggesting the existence of an additional brain system implicated in the integration of internal and environmental cues for reproduction.
PubMed: 38239387
DOI: 10.3389/fnana.2023.1301651 -
The Journal of Neuroscience : the... Feb 2024The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However,...
The suprachiasmatic nucleus (SCN) is the central clock for circadian rhythms. Animal studies have revealed daily rhythms in the neuronal activity in the SCN. However, the circadian activity of the human SCN has remained elusive. In this study, to reveal the diurnal variation of the SCN activity in humans, we localized the SCN by employing an areal boundary mapping technique to resting-state functional images and investigated the SCN activity using perfusion imaging. In the first experiment ( = 27, including both sexes), we scanned each participant four times a day, every 6 h. Higher activity was observed at noon, while lower activity was recorded in the early morning. In the second experiment ( = 20, including both sexes), the SCN activity was measured every 30 min for 6 h from midnight to dawn. The results showed that the SCN activity gradually decreased and was not associated with the electroencephalography. Furthermore, the SCN activity was compatible with the rodent SCN activity after switching off the lights. These results suggest that the diurnal variation of the human SCN follows the zeitgeber cycles of nocturnal and diurnal mammals and is modulated by physical lights rather than the local time.
Topics: Male; Animals; Female; Humans; Circadian Rhythm; Suprachiasmatic Nucleus; Rodentia; Mammals; Neurons
PubMed: 38238074
DOI: 10.1523/JNEUROSCI.1730-23.2024 -
Neural Regeneration Research Sep 2024Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer's disease. A predominant function of the retina is circadian synchronization, carrying...
Dysfunction in circadian rhythms is a common occurrence in patients with Alzheimer's disease. A predominant function of the retina is circadian synchronization, carrying information to the brain through the retinohypothalamic tract, which projects to the suprachiasmatic nucleus. Notably, Alzheimer's disease hallmarks, including amyloid-β, are present in the retinas of Alzheimer's disease patients, followed/associated by structural and functional disturbances. However, the mechanistic link between circadian dysfunction and the pathological changes affecting the retina in Alzheimer's disease is not fully understood, although some studies point to the possibility that retinal dysfunction could be considered an early pathological process that directly modulates the circadian rhythm.
PubMed: 38227523
DOI: 10.4103/1673-5374.390962 -
IScience Jan 2024The biological rhythms governed by negative feedback loops have undergone extensive investigation. However, developing reliable and versatile warning signals to predict...
The biological rhythms governed by negative feedback loops have undergone extensive investigation. However, developing reliable and versatile warning signals to predict periodic fluctuations in physiological processes and behaviors associated with these rhythms remains a challenge. Here, we monitored the heart rate and tracked ovulation dates of 91 fertile women. The finding strongly links the velocity (derivative) of heart rate with ovulation in menstrual cycles, providing a predictive warning signal. Similarly, an analysis of calcium signaling in the suprachiasmatic nucleus (SCN) of mice reveals that the maximum velocity of rising calcium signal aligns with locomotor activity offsets. To demonstrate the generality of derivative-transitions link, numerical simulations using a negative feedback loop model were conducted. Statistical analysis indicated that over 90% of the oscillations exhibited a correlation between maximum velocity and transition points. Consequently, the maximum velocity derived from oscillatory curves holds significant potential as an early warning signal for critical transitions.
PubMed: 38226166
DOI: 10.1016/j.isci.2023.108716 -
Biology of Sex Differences Jan 2024Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota-gut-brain axis in the regulation of...
RATIONALE
Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota-gut-brain axis in the regulation of feeding behavior has emerged during the last decades but its relationships with the circadian rhythm remains poorly documented. Thus, we aimed to characterize the circadian clock genes expression in peripheral and central tissues in the activity-based anorexia mouse model (ABA), as well as the dynamics of the gut-microbiota composition.
METHODS
From day 1 to day 17, male and female C57Bl/6 mice were submitted or not to the ABA protocol (ABA and control (CT) groups), which combines a progressive limited access to food and a free access to a running wheel. At day 17, fasted CT and ABA mice were euthanized after either resting (EoR) or activity (EoA) phase (n = 10-12 per group). Circadian clock genes expression was assessed by RT-qPCR on peripheral (liver, colon and ileum) and central (hypothalamic suprachiasmatic nucleus or SCN) tissues. Cecal bacterial taxa abundances were evaluated by qPCR. Data were compared by two-way ANOVA followed by post-tests.
RESULTS
ABA mice exhibited a lower food intake, a body weight loss and an increase of diurnal physical activity that differ according with the sex. Interestingly, in the SCN, only ABA female mice exhibited altered circadian clock genes expression (Bmal1, Per1, Per2, Cry1, Cry2). In the intestinal tract, modification of clock genes expression was also more marked in females compared to males. For instance, in the ileum, female mice showed alteration of Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Rev-erbα mRNA levels, while only Per2 and Cry1 mRNAs were affected by ABA model in males. By contrast, in the liver, clock genes expression was more markedly affected in males compared to females in response to ABA. Finally, circadian variations of gut-bacteria abundances were observed in both male and female mice and sex-dependent alteration were observed in response to the ABA model.
CONCLUSIONS
This study shows that alteration of circadian clock genes expression at both peripheral and central levels occurs in response to the ABA model. In addition, our data underline that circadian variations of the gut-microbiota composition are sex-dependent.
Topics: Animals; Female; Male; Mice; Anorexia; ARNTL Transcription Factors; Circadian Rhythm; Gene Expression; Microbiota; RNA, Messenger; CLOCK Proteins
PubMed: 38217033
DOI: 10.1186/s13293-023-00576-x -
The American Journal of Geriatric... Jun 2024Alterations in the suprachiasmatic nucleus due to underlying pathologies disrupt the circadian rhythms in people living with dementia (PLWD). Circadian rhythms... (Meta-Analysis)
Meta-Analysis
The Effects of Light Therapy on Sleep, Depression, Neuropsychiatric Behaviors, and Cognition Among People Living With Dementia: A Meta-Analysis of Randomized Controlled Trials.
OBJECTIVE
Alterations in the suprachiasmatic nucleus due to underlying pathologies disrupt the circadian rhythms in people living with dementia (PLWD). Circadian rhythms significantly impact sleep, emotional, and cognitive functions, with its synchronization depending on light exposure. We performed a meta-analysis to evaluate the effects of light therapy on sleep, depression, neuropsychiatric behaviors, and cognition among PLWD.
METHODS
A systematic search was conducted in Cochrane, ClinicalTrials.gov, Embase, EBSCOhost, Ovid-MEDLINE, PubMed, Scopus, Web of Science, and CINAHL databases. The pooled effect size was calculated using the Hedges' g with random-effects model adopted in comprehensive meta-analysis software. The Cochrane risk of bias (RoB 2.0) tool evaluated the quality of studies, while Cochrane's Q and I² tests assessed heterogeneity.
RESULTS
A total of 24 studies with 1,074 participants were included. Light therapy demonstrated small-to-medium effects on improving sleep parameters: total sleep time (Hedges' g = 0.19), wake after sleep onset (Hedges' g = 0.24), sleep efficiency (Hedges' g = 0.31), sleep latency (Hedges' g = 0.35), circadian rhythm (acrophase: Hedges' g = 0.36; amplitude: Hedges' g = 0.43), number of night awakenings (Hedges' g = 0.37), sleep disturbance (Hedges'g = 0.45), and sleep quality (Hedges' g = 0.60). Light therapy showed small-to-medium effect on reducing depression (Hedges' g = -0.46) with medium-to-large effect on cyclical function (Hedges' g = -0.68) and mood-related signs and symptoms (Hedges' g = -0.84) subscales. Light therapy also demonstrated small effect on reducing neuropsychiatric behaviors (Hedges' g = -0.34) with medium-to-large effect on agitation (Hedges' g = -0.65), affective symptom (Hedges' g = -0.70), psychosis (Hedges' g = -0.72), and melancholic behavior (Hedges' g = -0.91) subscales. Additionally, light therapy also improved cognition (Hedges' g = 0.39).
CONCLUSION
Light therapy could be used as a supportive therapy to improve sleep, depression, cognition, and neuropsychiatric behaviors among PLWD.
Topics: Humans; Circadian Rhythm; Cognition; Dementia; Depression; Phototherapy; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders
PubMed: 38216355
DOI: 10.1016/j.jagp.2023.12.010 -
Frontiers in Endocrinology 2023The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level...
The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.
BACKGROUND
The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN. SCN VIP neurons are known to regulate circadian rhythms and reproductive function.
METHODS
To specifically study SCN VIP neurons, we generated a novel knock out mouse line by conditionally deleting the SCN enriched transcription factor, Ventral Anterior Homeobox 1 (Vax1), in VIP neurons (Vax1; Vax1:Vip).
RESULTS
We found that Vax1 females presented with lengthened estrous cycles, reduced circulating estrogen, and increased depressive-like behavior. Further, Vax1 males and females presented with a shortened circadian period in locomotor activity and SCN circadian period. On a molecular level, the shortening of the SCN period was driven, at least partially, by a direct regulatory role of VAX1 on the circadian clock genes and . Interestingly, Vax1 females presented with increased expression of arginine vasopressin () in the paraventricular nucleus, which resulted in increased circulating corticosterone. SCN VIP and AVP neurons regulate the reproductive gonadotropin-releasing hormone (GnRH) and kisspeptin neurons. To determine how the reproductive neuroendocrine network was impacted in Vax1 mice, we assessed GnRH sensitivity to a kisspeptin challenge . We found that GnRH neurons in Vax1 females, but not males, had an increased sensitivity to kisspeptin, leading to increased luteinizing hormone release. Interestingly, Vax1 males showed a small, but significant increase in total sperm and a modest delay in pubertal onset. Both male and female Vax1 mice were fertile and generated litters comparable in size and frequency to controls.
CONCLUSION
Together, these data identify VAX1 in SCN VIP neurons as a neurological overlap between circadian timekeeping, female reproduction, and depressive-like symptoms in mice, and provide novel insight into the role of SCN VIP neurons.
Topics: Male; Female; Animals; Mice; Transcription Factors; Vasoactive Intestinal Peptide; Kisspeptins; Semen; Suprachiasmatic Nucleus; Reproduction; Neurons; Circadian Rhythm; Gonadotropin-Releasing Hormone; Neuropeptides; Homeodomain Proteins
PubMed: 38205198
DOI: 10.3389/fendo.2023.1269672 -
Journal of Sleep Research Jan 2024The circuitry underlying the initiation, maintenance, and coordination of wakefulness, rapid eye movement sleep, and non-rapid eye movement sleep is not thoroughly... (Review)
Review
The circuitry underlying the initiation, maintenance, and coordination of wakefulness, rapid eye movement sleep, and non-rapid eye movement sleep is not thoroughly understood. Sleep is thought to arise due to decreased activity in the ascending reticular arousal system, which originates in the brainstem and awakens the thalamus and cortex during wakefulness. Despite the conventional association of sleep-wake states with hippocampal rhythms, the mutual influence of the hippocampal formation in regulating vigilance states has been largely neglected. Here, we focus on the subiculum, the main output region of the hippocampal formation. The subiculum, particulary the ventral part, sends extensive monosynaptic projections to crucial regions implicated in sleep-wake regulation, including the thalamus, lateral hypothalamus, tuberomammillary nucleus, basal forebrain, ventrolateral preoptic nucleus, ventrolateral tegmental area, and suprachiasmatic nucleus. Additionally, second-order projections from the subiculum are received by the laterodorsal tegmental nucleus, locus coeruleus, and median raphe nucleus, suggesting the potential involvement of the subiculum in the regulation of the sleep-wake cycle. We also discuss alterations in the subiculum observed in individuals with sleep disorders and in sleep-deprived mice, underscoring the significance of investigating neuronal communication between the subiculum and pathways promoting both sleep and wakefulness.
PubMed: 38196146
DOI: 10.1111/jsr.14134 -
Molecular Neurodegeneration Jan 2024Tauopathies, a group of neurodegenerative diseases that includes Alzheimer's disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm... (Review)
Review
Tauopathies, a group of neurodegenerative diseases that includes Alzheimer's disease, commonly lead to disturbances in sleep-wake patterns and circadian rhythm disorders. The circadian rhythm, a recurring 24-hour cycle governing human biological activity, is regulated by the hypothalamic suprachiasmatic nucleus (SCN) and endogenous transcriptional-translational feedback loops. Surprisingly, little attention has been given to investigating tauopathy-driven neuropathology in the SCN and the repercussions of SCN and circadian gene dysfunction in the human brain affected by tauopathies. This review aims to provide an overview of the current literature on the vulnerability of the SCN in tauopathies in humans. Emphasis is placed on elucidating the neuronal and glial changes contributing to the widespread disruption of the molecular circadian clock. Furthermore, this review identifies areas of knowledge requiring further investigation.
Topics: Animals; Humans; Neuroglia; Tauopathies; Suprachiasmatic Nucleus; Alzheimer Disease; Models, Animal
PubMed: 38195580
DOI: 10.1186/s13024-023-00695-4 -
Frontiers in Neuroscience 2023The suprachiasmatic nucleus (SCN) of the hypothalamus is the master circadian clock in mammals. SCN neurons exhibit circadian Ca rhythms in the cytosol, which is thought...
The suprachiasmatic nucleus (SCN) of the hypothalamus is the master circadian clock in mammals. SCN neurons exhibit circadian Ca rhythms in the cytosol, which is thought to act as a messenger linking the transcriptional/translational feedback loop (TTFL) and physiological activities. Transcriptional regulation occurs in the nucleus in the TTFL model, and Ca-dependent kinase regulates the clock gene transcription. However, the Ca regulatory mechanisms between cytosol and nucleus as well as the ionic origin of Ca rhythms remain unclear. In the present study, we monitored circadian-timescale Ca dynamics in the nucleus and cytosol of SCN neurons at the single-cell and network levels. We observed robust nuclear Ca rhythm in the same phase as the cytosolic rhythm in single SCN neurons and entire regions. Neuronal firing inhibition reduced the amplitude of both nuclear and cytosolic Ca rhythms, whereas blocking of Ca release from the endoplasmic reticulum (ER) via ryanodine and inositol 1,4,5-trisphosphate (IP) receptors had a minor effect on either Ca rhythms. We conclude that the in-phasic circadian Ca rhythms in the cytosol and nucleus are mainly driven by Ca influx from the extracellular space, likely through the nuclear pore. It also raises the possibility that nuclear Ca rhythms directly regulate transcription
PubMed: 38178840
DOI: 10.3389/fnins.2023.1323565