-
Development, Growth & Differentiation Feb 2024Nuclear receptor subfamily 2 group F (Nr2f) proteins are essential for brain development in mice, but little is known about their precise roles and their evolutionary...
Nuclear receptor subfamily 2 group F (Nr2f) proteins are essential for brain development in mice, but little is known about their precise roles and their evolutionary diversification. In the present study, the expression patterns of major nr2f genes (nr2f1a, nr2f1b, and nr2f2) during early brain development were investigated in zebrafish. Comparisons of their expression patterns revealed similar but temporally and spatially distinct patterns after early somite stages in the brain. Frameshift mutations in the three nr2f genes, achieved using the CRISPR/Cas9 method, resulted in a smaller telencephalon and smaller eyes in the nr2f1a mutants; milder forms of those defects were present in the nr2f1b and nr2f2 mutants. Acridine orange staining revealed enhanced cell death in the brain and/or eyes in all nr2f homozygous mutants. The expression of regional markers in the brain did not suggest global defects in brain regionalization; however, shha expression in the preoptic area and hypothalamus, as well as fgf8a expression in the anterior telencephalon, was disturbed in nr2f1a and nr2f1b mutants, potentially leading to a defective telencephalon. Specification of the retina and optic stalk was also significantly affected. The overexpression of nr2f1b by injection of mRNA disrupted the anterior brain at a high dose, and the expression of pax6a in the eyes and fgf8a in the telencephalon at a low dose. The results of these loss- and gain-of-function approaches showed that nr2f genes regulate the development of the telencephalon and eyes in zebrafish embryos.
Topics: Animals; Mice; Brain; Eye; Gene Expression Regulation, Developmental; Telencephalon; Zebrafish; Zebrafish Proteins; Nuclear Receptor Subfamily 1, Group F, Member 2; Orphan Nuclear Receptors
PubMed: 38263801
DOI: 10.1111/dgd.12912 -
Journal of Applied Microbiology Apr 2024To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms...
AIMS
To examine the influence of GED on the gut microbiota and metabolites using a bilateral ovariectomized (OVX) rat model. We tried to elucidate the underlying mechanisms of GED in the treatment of menopausal hot flashes.
METHODS AND RESULTS
16S rRNA sequencing, metabonomics, molecular biological analysis, and fecal microbiota transplantation (FMT) were conducted to elucidate the mechanisms by which GED regulates the gut microbiota. GED significantly reduced OVX-induced hot flashes and improved disturbances in the gut microbiota metabolites. Moreover, FMT validated that the gut microbiota can trigger hot flashes, while GED can alleviate hot flash symptoms by modulating the composition of the gut microbiota. Specifically, GED upregulated the abundance of Blautia, thereby increasing l(+)-ornithine levels for the treatment of menopausal hot flashes. Additionally, GED affected endothelial nitric oxide synthase and heat shock protein 70 (HSP70) levels in the hypothalamic preoptic area by changing the gut microbiota composition.
CONCLUSIONS
Our study illuminated the underlying mechanisms by which GED attenuated the hot flashes through modulation of the gut microbiota and explored the regulatory role of the gut microbiota on HSP70 expression in the preoptic anterior hypothalamus, thereby establishing a foundation for further exploration of the role of the gut-brain axis in hot flashes.
Topics: Animals; Gastrointestinal Microbiome; Hot Flashes; Rats; Female; Drugs, Chinese Herbal; Menopause; Fecal Microbiota Transplantation; Ovariectomy; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Metabolome
PubMed: 38253409
DOI: 10.1093/jambio/lxae016 -
Journal of Experimental Zoology. Part... Apr 2024Reptiles display considerable diversity in reproductive behavior, making them great models to study the neuroendocrine control of reproductive behavior. Many reptile... (Review)
Review
Reptiles display considerable diversity in reproductive behavior, making them great models to study the neuroendocrine control of reproductive behavior. Many reptile species are seasonally breeding, such that they become reproductively active during their breeding season and regress to a nonreproductive state during their nonbreeding season, with this transition often prompted by environmental cues. In this review, we will focus on summarizing the neural and neuroendocrine mechanisms controlling reproductive behavior. Three major areas of the brain are involved in reproductive behavior: the preoptic area (POA), amygdala, and ventromedial hypothalamus (VMH). The POA and VMH are sexually dimorphic areas, regulating behaviors in males and females respectively, and all three areas display seasonal plasticity. Lesions to these areas disrupt the onset and maintenance of reproductive behaviors, but the exact roles of these regions vary between sexes and species. Different hormones influence these regions to elicit seasonal transitions. Circulating testosterone (T) and estradiol (E2) peak during the breeding season and their influence on reproduction is well-documented across vertebrates. The conversion of T into E2 and 5α-dihydrotestosterone can also affect behavior. Melatonin and corticosterone have generally inhibitory effects on reproductive behavior, while serotonin and other neurohormones seem to stimulate it. In general, there is relatively little information on the neuroendocrine control of reproduction in reptiles compared to other vertebrate groups. This review highlights areas that should be considered for future areas of research.
Topics: Female; Male; Animals; Reptiles; Brain; Reproduction; Testosterone; Sexual Behavior, Animal
PubMed: 38247297
DOI: 10.1002/jez.2783 -
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 -
Diabetes, Obesity & Metabolism Apr 2024Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the...
Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, β3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.
Topics: Mice; Animals; Electroacupuncture; Sympathetic Nervous System; Obesity; Adipose Tissue, White; Adipose Tissue, Brown; Thermogenesis; Sense Organs
PubMed: 38229447
DOI: 10.1111/dom.15444 -
The Journal of Headache and Pain Jan 2024Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a...
BACKGROUND
Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition.
METHODS
We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients.
RESULTS
Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found.
CONCLUSIONS
We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.
Topics: Humans; Cluster Headache; Pain; Headache; Hypothalamus; Lithium Compounds
PubMed: 38212704
DOI: 10.1186/s10194-023-01711-0 -
Current Biology : CB Feb 2024Animals must maintain physiological processes within an optimal temperature range despite changes in their environment. Through behavioral assays, whole-brain functional...
Animals must maintain physiological processes within an optimal temperature range despite changes in their environment. Through behavioral assays, whole-brain functional imaging, and neural ablations, we show that larval zebrafish, an ectothermic vertebrate, achieves thermoregulation through homeostatic navigation-non-directional and directional movements toward the temperature closest to its physiological setpoint. A brain-wide circuit encompassing several brain regions enables this behavior. We identified the preoptic area of the hypothalamus (PoA) as a key brain structure in triggering non-directional reorientation when thermal conditions are worsening. This result shows an evolutionary conserved role of the PoA as principal thermoregulator of the brain also in ectotherms. We further show that the habenula (Hb)-interpeduncular nucleus (IPN) circuit retains a short-term memory of the sensory history to support the generation of coherent directed movements even in the absence of continuous sensory cues. We finally provide evidence that this circuit may not be exclusive for temperature but may convey a more abstract representation of relative valence of physiologically meaningful stimuli regardless of their specific identity to enable homeostatic navigation.
Topics: Animals; Zebrafish; Preoptic Area; Habenula; Larva; Body Temperature Regulation
PubMed: 38211586
DOI: 10.1016/j.cub.2023.12.030 -
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 -
ELife Dec 2023Evidence suggests that estradiol-sensing preoptic area GABA neurons are involved in the preovulatory surge mechanism necessary for ovulation. In vivo CRISPR-Cas9 editing...
Evidence suggests that estradiol-sensing preoptic area GABA neurons are involved in the preovulatory surge mechanism necessary for ovulation. In vivo CRISPR-Cas9 editing was used to achieve a 60-70% knockdown in estrogen receptor alpha (ESR1) expression by GABA neurons located within the regions of the rostral periventricular area of the third ventricle (RP3V) and medial preoptic nuclei (MPN) in adult female mice. Mice exhibited variable reproductive phenotypes with the only significant finding being mice with bilateral ESR1 deletion in RP3V GABA neurons having reduced cFos expression in gonadotropin-releasing hormone (GnRH) neurons at the time of the surge. One sub-population of RP3V GABA neurons expresses kisspeptin. Re-grouping ESR1-edited mice on the basis of their RP3V kisspeptin expression revealed a highly consistent phenotype; mice with a near-complete loss of kisspeptin immunoreactivity displayed constant estrus and failed to exhibit surge activation but retained pulsatile luteinizing hormone (LH) secretion. These observations demonstrate that ESR1-expressing GABA-kisspeptin neurons in the RP3V are essential for the murine preovulatory LH surge mechanism.
Topics: Mice; Female; Animals; Kisspeptins; CRISPR-Cas Systems; Gonadotropin-Releasing Hormone; GABAergic Neurons; Estrous Cycle; gamma-Aminobutyric Acid
PubMed: 38126277
DOI: 10.7554/eLife.90959