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Biology of Sex Differences Dec 2023ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological...
BACKGROUND
ESR2, a nuclear estrogen receptor also known as estrogen receptor β, is expressed in the brain and contributes to the actions of estrogen in various physiological phenomena. However, its expression profiles in the brain have long been debated because of difficulties in detecting ESR2-expressing cells. In the present study, we aimed to determine the distribution of ESR2 in rodent brains, as well as its sex and interspecies differences, using immunohistochemical detection with a well-validated anti-ESR2 antibody (PPZ0506).
METHODS
To determine the expression profiles of ESR2 protein in rodent brains, whole brain sections from mice and rats of both sexes were subjected to immunostaining for ESR2. In addition, to evaluate the effects of circulating estrogen on ESR2 expression profiles, ovariectomized female mice and rats were treated with low or high doses of estrogen, and the resulting numbers of ESR2-immunopositive cells were analyzed. Welch's t-test was used for comparisons between two groups for sex differences, and one-way analysis of variance followed by the Tukey-Kramer test were used for comparisons among multiple groups with different estrogen treatments.
RESULTS
ESR2-immunopositive cells were observed in several subregions of mouse and rat brains, including the preoptic area, extended amygdala, hypothalamus, mesencephalon, and cerebral cortex. Their distribution profiles exhibited sex and interspecies differences. In addition, low-dose estrogen treatment in ovariectomized female mice and rats tended to increase the numbers of ESR2-immunopositive cells, whereas high-dose estrogen treatment tended to decrease these numbers.
CONCLUSIONS
Immunohistochemistry using the well-validated PPZ0506 antibody revealed a more localized expression of ESR2 protein in rodent brains than has previously been reported. Furthermore, there were marked sex and interspecies differences in its distribution. Our histological analyses also revealed estrogen-dependent changes in ESR2 expression levels in female brains. These findings will be helpful for understanding the ESR2-mediated actions of estrogen in the brain.
Topics: Animals; Female; Male; Rats; Brain; Estrogen Receptor beta; Estrogens; Hypothalamus; Receptors, Estrogen
PubMed: 38111056
DOI: 10.1186/s13293-023-00574-z -
The Journal of Comparative Neurology Feb 2024The secondary general visceral sensory nucleus (SVN) receives ascending fibers from the commissural nucleus of Cajal (NCC), or the primary general visceral sensoru in...
The secondary general visceral sensory nucleus (SVN) receives ascending fibers from the commissural nucleus of Cajal (NCC), or the primary general visceral sensoru in the medulla oblongata of teleosts. However, the full set of fiber connections of the SVN have been studied only in the Nile tilapia. We have investigated the connections of the SVN in goldfish by tracer injection experiments to the nucleus. We paid special attention to the possible presence of spinal afferents, since the spinal cord projects to the lateral parabrachial nucleus, or the presumed homologue of SVN, in mammals. We found that the SVN indeed receives spinal projections. Spinal terminals were restricted to a region ventrolaterally adjacent to the terminal zone of NCC fibers, suggesting that the SVN can be subdivided into two subnuclei: the commissural nucleus-recipient (SVNc) and spinal-recipient (SVNsp) subnuclei. Tracer injections to the SVNc and SVNsp as well as reciprocal injections to the diencephalon revealed that both subnuclei project directly to diencephalic structures, such as the posterior thalamic nucleus and nucleus of lateral recess, although diencephalic projections of the SVNsp were rather sparse. The SVNsp appears to send fibers to more wide-spread targets in the preoptic area than the SVNc does. The SVNc projects to the telencephalon, while the SVNsp sends scarce or possibly no fibers to the telencephalon. Another notable difference was that the SVNsp gives rise to massive projections to the dorsal diencephalon (ventromedial thalamic, central posterior thalamic, and periventricular posterior tubercular nuclei). These differential connections of the subnuclei may reflect discrete functional significances of the general visceral sensory information mediated by the medulla oblongata and spinal cord.
Topics: Animals; Goldfish; Diencephalon; Telencephalon; Medulla Oblongata; Preoptic Area; Mammals
PubMed: 38104256
DOI: 10.1002/cne.25566 -
Current Biology : CB Jan 2024Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals,...
Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals, MAs), resulting in sleep fragmentation. The preoptic area of the hypothalamus (POA) is crucial for sleep control. However, how POA neurons contribute to the regulation of MAs and thereby impact sleep quality is unknown. Using fiber photometry in mice, we examine the activity of genetically defined POA subpopulations during sleep. We find that POA glutamatergic neurons are rhythmically activated in synchrony with an infraslow rhythm in the spindle band of the electroencephalogram during non-rapid eye movement sleep (NREMs) and are transiently activated during MAs. Optogenetic stimulation of these neurons promotes MAs and wakefulness. Exposure to acute social defeat stress fragments NREMs and significantly increases the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. By reducing MAs, optogenetic inhibition during spontaneous sleep and after stress consolidates NREMs. Monosynaptically restricted rabies tracing reveals that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. In particular, presynaptic glutamatergic neurons in the lateral hypothalamus become activated after stress, and stimulating their projections to the POA promotes MAs and wakefulness. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.
Topics: Mice; Animals; Sleep Deprivation; Sleep; Hypothalamus; Preoptic Area; Neurons; Wakefulness
PubMed: 38096820
DOI: 10.1016/j.cub.2023.11.035 -
Journal of Experimental Zoology. Part... Apr 2024This review article includes a literature review of synteny analysis of the amphibian gonadotropin-releasing hormone (GnRH) genes, the distribution of GnRH 1 and GnRH2... (Review)
Review
This review article includes a literature review of synteny analysis of the amphibian gonadotropin-releasing hormone (GnRH) genes, the distribution of GnRH 1 and GnRH2 neurons in the central nervous system of amphibians, the function and regulation of hypophysiotropic GnRH1, and the function of GnRH1 in amphibian reproductive behaviors. It is generally accepted that GnRH is the key regulator of the hypothalamic-pituitary-gonadal axis. Three independent GnRH genes, GnRH1, GnRH2, and GnRH3, have been identified in vertebrates. Previous genome synteny analyses suggest that there are likely just two genes, gnrh1 and gnrh2, in amphibians. In three groups of amphibians: Anura, Urodela, and Gymnophiona, the distributions of GnRH1 and GnRH2 neurons in the central nervous system have also been previously reported. Moreover, these neuronal networks were determined to be structurally independent in all species examined. The somata of GnRH1 neurons are located in the terminal nerve, medial septum (MS), and preoptic area (POA), and some GnRH1 neurons in the MS and POA project into the median eminence. In contrast, the somata of GnRH2 neurons are located in the midbrain tegmentum. In amphibians, GnRH1 neurons originate from the embryonic olfactory placode, while GnRH2 neurons originate from the midbrain. The characterization and feedback regulation mechanisms of hypophysiotropic GnRH1 neurons in amphibians, the involvement of GnRH1 in amphibian reproductive behavior, and its possible mechanism of action should be elucidated in future.
Topics: Animals; Gonadotropin-Releasing Hormone; Reproduction; Vertebrates; Amphibians
PubMed: 38084833
DOI: 10.1002/jez.2769 -
Neuroendocrinology 2024In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve...
INTRODUCTION
In nurturing systems, the oxytocin (Oxt)-oxytocin receptor (Oxtr) system is important for parturition, and essential for lactation and parental behavior. Among the nerve nuclei that express Oxtr, the lateral septal nucleus (LS) and medial preoptic area (MPOA) are representative regions that control maternal behavior.
METHODS
We investigated the role of Oxtr- and Oxtr-expressing neurons, located in the LS and MPOA, in regulating maternal behavior by regulating Oxtr expression in a region-specific manner using recombinant mice and adeno-associated viruses. We quantified the prolactin (Prl) concentrations in the pituitary gland and plasma when Oxtr expression in the MPOA was reduced.
RESULTS
The endogenous Oxtr gene in the neurons of the LS did not seem to play an essential role in maternal behavior. Conversely, decreased Oxtr expression in the MPOA increased the frequency of pups being left outside the nest and reduced their survival rate. Deletion of Oxtr in MPOA neurons prevented elevation of Prl levels in plasma and pituitary at postpartum day 2.
DISCUSSION/CONCLUSION
Oxtr-expressing neurons in the MPOA are involved in the postpartum production of Prl. We confirmed the essential functions of Oxtr-expressing neurons and the Oxtr gene itself in the MPOA for the sustainability of maternal behavior, which involved Oxtr-dependent induction of Prl.
Topics: Animals; Receptors, Oxytocin; Maternal Behavior; Lactation; Preoptic Area; Female; Neurons; Prolactin; Mice; Septal Nuclei; Mice, Inbred C57BL; Mice, Transgenic; Oxytocin; Pituitary Gland
PubMed: 38071956
DOI: 10.1159/000535362 -
Neuroscience Jan 2024The paraventricular nucleus of the thalamus (PVT) sends dense projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the...
The paraventricular nucleus of the thalamus (PVT) sends dense projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and the lateral region of central nucleus of the amygdala (CeL). Projection specific modulation of these pathways has been shown to regulate appetitive and aversive behavioral responses. The present investigation applied an intersectional monosynaptic rabies tracing approach to quantify the brain-wide sources of afferent input to PVT neurons that primarily project to the NAcSh, BSTDL and CeL. The results demonstrate that these projection neurons receive monosynaptic input from similar brain regions. The prefrontal cortex and the ventral subiculum of the hippocampus were major sources of input to the PVT projection neurons. In addition, the lateral septal nucleus, thalamic reticular nucleus and the hypothalamic medial preoptic area, dorsomedial, ventromedial, and arcuate nuclei were sources of input. The subfornical organ, parasubthalamic nucleus, periaqueductal gray matter, lateral parabrachial nucleus, and nucleus of the solitary tract were consistent but lesser sources of input. This input-output relationship is consistent with recent observations that PVT neurons have axons that bifurcate extensively to divergently innervate the NAcSh, BSTDL and CeL.
Topics: Nucleus Accumbens; Central Amygdaloid Nucleus; Paraventricular Hypothalamic Nucleus; Hypothalamus; Neurons; Neural Pathways
PubMed: 38056620
DOI: 10.1016/j.neuroscience.2023.11.033 -
Communications Biology Dec 2023Calcitonin receptor (Calcr) and its brain ligand amylin in the medial preoptic area (MPOA) are found to be critically involved in infant care and social contact...
Calcitonin receptor (Calcr) and its brain ligand amylin in the medial preoptic area (MPOA) are found to be critically involved in infant care and social contact behaviors in mice. In primates, however, the evidence is limited to an excitotoxic lesion study of the Calcr-expressing MPOA subregion (cMPOA) in a family-living primate species, the common marmoset. The present study utilized pharmacological manipulations of the cMPOA and shows that reversible inactivation of the cMPOA abolishes infant-care behaviors in sibling marmosets without affecting other social or non-social behaviors. Amylin-expressing neurons in the marmoset MPOA are distributed in the vicinity of oxytocin neurons in the anterior paraventricular nucleus of the hypothalamus. While amylin infusion facilitates infant carrying selectively, an oxytocin's inverse agonist, atosiban, reduces physical contact with non-infant family members without grossly affecting infant care. These data suggest that the amylin and oxytocin signaling mediate intrafamilial social interactions in a complementary manner in marmosets.
Topics: Humans; Mice; Animals; Preoptic Area; Oxytocin; Callithrix; Islet Amyloid Polypeptide; Drug Inverse Agonism; Social Behavior
PubMed: 38052969
DOI: 10.1038/s42003-023-05593-5 -
Neuroscience Letters Jan 2024Persistent post-ischemic alterations to the hypothalamic-pituitary-adrenal (HPA) axis occur following global cerebral ischemia (GCI) in rodents. However, similar effects...
Persistent post-ischemic alterations to the hypothalamic-pituitary-adrenal (HPA) axis occur following global cerebral ischemia (GCI) in rodents. However, similar effects on hypothalamic-pituitary-gonadal (HPG) axis activation remain to be determined. Therefore, this study evaluated the effects of GCI in adult female rats (via four-vessel occlusion) on the regularity of the estrous cycle for 24-days post ischemia. A second objective aimed to assess persistent alterations of HPG axis activation through determination of the expression of estrogen receptor alpha (ERα), kisspeptin (Kiss1), and gonadotropin-inhibitory hormone (GnIH/RFamide-related peptide; RFRP3) in the medial preoptic area (POA), arcuate nucleus (ARC), dorsomedial nucleus (DMH) of the hypothalamus, and CA1 of the hippocampus 25 days post ischemia. Expression of glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN) and CA1 served as a proxy of altered HPA axis activation. Our findings demonstrated interruption of the estrous cycle in 87.5 % of ischemic rats, marked by persistent diestrus, lasting on average 11.86 days. Moreover, compared to sham-operated controls, ischemic female rats showed reduced Kiss1 expression in the hypothalamic ARC and POA, concomitant with elevated ERα in the ARC and increased GnIH in the DMH and CA1. Reduced GR expression in the CA1 was associated with increased GR-immunoreactivity in the PVN, indicative of lasting dysregulation of HPA axis activation. Together, these findings demonstrate GCI disruption of female rats' estrous cycle over multiple days, with a lasting impact on HPG axis regulators within the reproductive axis.
Topics: Rats; Female; Animals; Hypothalamo-Hypophyseal System; Kisspeptins; Hypothalamic-Pituitary-Gonadal Axis; Estrogen Receptor alpha; Pituitary-Adrenal System; Hypothalamus; Estrous Cycle; Brain Ischemia; Cerebral Infarction; Periodicity
PubMed: 38048875
DOI: 10.1016/j.neulet.2023.137578 -
Frontiers in Neuroscience 2023Sexual motivation is an abstract concept referring to the mechanisms determining the responsivity to sexually relevant stimuli. This responsivity determines the... (Review)
Review
Sexual motivation is an abstract concept referring to the mechanisms determining the responsivity to sexually relevant stimuli. This responsivity determines the likelihood of producing a sexual response and the intensity of that response. Both responsivity to stimuli and the likelihood of making a response as well as the intensity of response are characteristics of an individual. Therefore, we need to assume that the concept of sexual motivation materializes in physiological mechanisms within the individual. The aim of the present communication is to analyze the requisites for the endeavor to materialize sexual motivation. The first requisite is to provide an operational definition, making the concept quantifiable. We show that parameters of copulatory behavior are inappropriate. We argue that the intensity of sexual approach behaviors provides the best estimate of sexual motivation in non-human animals, whereas the magnitude of genital responses is an exquisite indicator of human sexual motivation. Having assured how to quantify sexual motivation, we can then proceed to the search for physiological or neurobiological underpinnings. In fact, sexual motivation only manifests itself in animals exposed to appropriate amounts of gonadal hormones. In female rats, the estrogen receptor α in the ventrolateral part of the ventromedial nucleus of the hypothalamus is necessary for the expression of sexual approach behaviors. In male rats, androgen receptors within the medial preoptic area are crucial. Thus, in rats sexual motivation can be localized to specific brain structures, and even to specific cells within these structures. In humans, it is not even known if sexual motivation is materialized in the brain or in peripheral structures. Substantial efforts have been made to determine the relationship between the activity of neurotransmitters and the intensity of sexual motivation, particularly in rodents. The results of this effort have been meager. Likewise, efforts of finding drugs to stimulate sexual motivation, particularly in women complaining of low sexual desire, have produced dismal results. In sum, it appears that the abstract concept of sexual motivation can be reliably quantified, and the neurobiological bases can be described in non-human animals. In humans, objective quantification is feasible, but the neurobiological substrate remains enigmatic.
PubMed: 38046659
DOI: 10.3389/fnins.2023.1285810 -
Comparative Biochemistry and... Feb 2024Using dominance hierarchies in juvenile rainbow trout (Oncorhynchus mykiss) as a model of chronic social stress in fish, we explored whether epigenetic transcriptional...
Using dominance hierarchies in juvenile rainbow trout (Oncorhynchus mykiss) as a model of chronic social stress in fish, we explored whether epigenetic transcriptional and post-transcriptional mechanisms are involved in the gene expression of corticotropin-releasing factor (crf) and 11β-hydroxysteroid dehydrogenase (11βhsd2), key factors involved in the regulation of the endocrine stress axis response. In juvenile rainbow trout pairs, subordinate individuals display sustained elevation of circulating cortisol concentrations. Cortisol production is controlled by the hypothalamic-pituitary-interrenal (HPI) axis in fish and initiated by CRF release from the preoptic area (POA). Given that crf is modulated during chronic social stress, and that such stress has been implicated in the epigenetic regulation of crf in other taxa, we probed a role for epigenetic regulation of crf transcript abundance in chronically stressed rainbow trout. We also investigated the regulation of the cortisol-metabolising enzyme 11βhsd2 in the POA, which is upregulated in subordinates. The potential involvement of DNA methylation and microRNAs (miRNAs) in the regulation of crf transcript abundance was investigated during social stress in the POA of fish, as was the potential involvement of miRNAs in 11βhsd2 regulation. Although transcript abundances of crf were elevated in subordinate fish after 4 days, DNA methylation profiles within putative promoter sequences upstream of the crf gene were not significantly affected by chronic stress. An inverse relationship between crf and its predicted posttranscriptional regulator miR-103a-3p in the POA suggests that miRNAs may be involved in mediating the effects of chronic social stress on key components of the endocrine stress axis.
Topics: Animals; Corticotropin-Releasing Hormone; Oncorhynchus mykiss; Hydrocortisone; Epigenesis, Genetic; Brain; MicroRNAs
PubMed: 38043640
DOI: 10.1016/j.cbpa.2023.111557