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Animals : An Open Access Journal From... Jun 2024Hyperthermia elicits several physiological and behavioral responses in livestock to restore thermal neutrality. Among these responses, vasodilation and sweating help to... (Review)
Review
Hyperthermia elicits several physiological and behavioral responses in livestock to restore thermal neutrality. Among these responses, vasodilation and sweating help to reduce core body temperature by increasing heat dissipation by radiation and evaporation. Thermoregulatory behaviors such as increasing standing time, reducing feed intake, shade-seeking, and limiting locomotor activity also increase heat loss. These mechanisms are elicited by the connection between peripheral thermoreceptors and cerebral centers, such as the preoptic area of the hypothalamus. Considering the importance of this thermoregulatory pathway, this review aims to discuss the hypothalamic control of hyperthermia in livestock, including the main physiological and behavioral changes that animals adopt to maintain their thermal stability.
PubMed: 38929364
DOI: 10.3390/ani14121745 -
Cells May 2024Sleep disruption is a frequent problem of advancing age, often accompanied by low-grade chronic central and peripheral inflammation. We examined whether chronic...
Sleep disruption is a frequent problem of advancing age, often accompanied by low-grade chronic central and peripheral inflammation. We examined whether chronic neuroinflammation in the preoptic and basal forebrain area (POA-BF), a critical sleep-wake regulatory structure, contributes to this disruption. We developed a targeted viral vector designed to overexpress tumor necrosis factor-alpha (TNFα), specifically in astrocytes (AAV5-GFAP-TNFα-mCherry), and injected it into the POA of young mice to induce heightened neuroinflammation within the POA-BF. Compared to the control (treated with AAV5-GFAP-mCherry), mice with astrocytic TNFα overproduction within the POA-BF exhibited signs of increased microglia activation, indicating a heightened local inflammatory milieu. These mice also exhibited aging-like changes in sleep-wake organization and physical performance, including (a) impaired sleep-wake functions characterized by disruptions in sleep and waking during light and dark phases, respectively, and a reduced ability to compensate for sleep loss; (b) dysfunctional VLPO sleep-active neurons, indicated by fewer neurons expressing c-fos after suvorexant-induced sleep; and (c) compromised physical performance as demonstrated by a decline in grip strength. These findings suggest that inflammation-induced dysfunction of sleep- and wake-regulatory mechanisms within the POA-BF may be a critical component of sleep-wake disturbances in aging.
Topics: Animals; Astrocytes; Aging; Preoptic Area; Mice; Tumor Necrosis Factor-alpha; Sleep; Basal Forebrain; Wakefulness; Male; Mice, Inbred C57BL; Neurons; Sleep Wake Disorders
PubMed: 38891027
DOI: 10.3390/cells13110894 -
ELife Jun 2024Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically...
Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POA→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POA→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POA→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POA→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.
Topics: Animals; Preoptic Area; Sleep, REM; Homeostasis; Mice; GABAergic Neurons; Male; Electroencephalography; Hypothalamic Area, Lateral
PubMed: 38884573
DOI: 10.7554/eLife.92095 -
The Journal of Physiological Sciences :... Jun 2024Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A...
Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.
Topics: Animals; Preoptic Area; Isoflurane; Adenosine; Neurons; Male; Anesthetics, Inhalation; Body Temperature; Hypothermia; Torpor; Mice; Proto-Oncogene Proteins c-fos
PubMed: 38867187
DOI: 10.1186/s12576-024-00927-2 -
Endocrine Journal Jun 2024In the early 2000s, metastin, an endogenous ligand for G protein-coupled receptor 54 (GPR54), was discovered in human placental extracts. In 2003, GPR54 receptor...
In the early 2000s, metastin, an endogenous ligand for G protein-coupled receptor 54 (GPR54), was discovered in human placental extracts. In 2003, GPR54 receptor mutations were found in a family with congenital hypogonadotropic hypogonadism. Metastin was subsequently renamed kisspeptin after its coding gene, Kiss1. Since then, studies in mice and other animals have revealed that kisspeptin is located at the apex of the hypothalamic-pituitary-gonadal axis and regulates reproductive functions by modulating gonadotropin-releasing hormone (GnRH). In rodents, kisspeptin (Kiss1) neurons localize to two regions, the hypothalamic arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). ARC Kiss1 neurons co-express neurokinin B (NKB) and dynorphin and are thus termed KNDy neurons. Kiss1 neurons in humans are concentrated in the infundibular nucleus (equivalent to the ARC), with few Kiss1 neurons localized to the preoptic area (equivalent to the AVPV), and the mechanisms underlying GnRH surge secretion in humans are poorly understood. However, peripheral administration of kisspeptin to humans promotes gonadotropin secretion, and administration of kisspeptin to patients with hypothalamic amenorrhea or congenital hypogonadotropic hypogonadism restores the pulsatile secretion of GnRH/luteinizing hormone. Thus, kisspeptin undoubtedly plays an important role in reproductive function in humans. Studies are currently underway to develop kisspeptin receptor agonists or antagonists for clinical application. Modification of KNDy neurons by NKB agonists/antagonists is also being attempted to develop therapeutic agents for various menstrual abnormalities, including polycystic ovary syndrome and menopausal hot flashes. Here, we review the role of kisspeptin in humans and its clinical applications.
PubMed: 38866494
DOI: 10.1507/endocrj.EJ24-0006 -
Genes, Brain, and Behavior Jun 2024Motherhood is a costly life-history transition accompanied by behavioral and neural plasticity necessary for offspring care. Motherhood in the monogamous prairie vole is...
Motherhood is a costly life-history transition accompanied by behavioral and neural plasticity necessary for offspring care. Motherhood in the monogamous prairie vole is associated with decreased pair bond strength, suggesting a trade-off between parental investment and pair bond maintenance. Neural mechanisms governing pair bonds and maternal bonds overlap, creating possible competition between the two. We measured mRNA expression of genes encoding receptors for oxytocin (oxtr), dopamine (d1r and d2r), mu-opioids (oprm1a), and kappa-opioids (oprk1a) within three brain areas processing salience of sociosensory cues (anterior cingulate cortex; ACC), pair bonding (nucleus accumbens; NAc), and maternal care (medial preoptic area; MPOA). We compared gene expression differences between pair bonded prairie voles that were never pregnant, pregnant (~day 16 of pregnancy), and recent mothers (day 3 of lactation). We found greater gene expression in the NAc (oxtr, d2r, oprm1a, and oprk1a) and MPOA (oxtr, d1r, d2r, oprm1a, and oprk1a) following the transition to motherhood. Expression for all five genes in the ACC was greatest for females that had been bonded for longer. Gene expression within each region was highly correlated, indicating that oxytocin, dopamine, and opioids comprise a complimentary gene network for social signaling. ACC-NAc gene expression correlations indicated that being a mother (oxtr and d1r) or maintaining long-term pair bonds (oprm1a) relies on the coordination of different signaling systems within the same circuit. Our study suggests the maternal brain undergoes changes that prepare females to face the trade-off associated with increased emotional investment in offspring, while also maintaining a pair bond.
Topics: Animals; Female; Arvicolinae; Receptors, Opioid, mu; Pair Bond; Maternal Behavior; Nucleus Accumbens; Pregnancy; Receptors, Oxytocin; Receptors, Opioid, kappa; Gyrus Cinguli; Preoptic Area; Receptors, Dopamine D1
PubMed: 38861664
DOI: 10.1111/gbb.12906 -
ELife Jun 2024Threat-response neural circuits are conserved across species and play roles in normal behavior and psychiatric diseases. Maladaptive changes in these neural circuits...
Threat-response neural circuits are conserved across species and play roles in normal behavior and psychiatric diseases. Maladaptive changes in these neural circuits contribute to stress, mood, and anxiety disorders. Active coping in response to stressors is a psychosocial factor associated with resilience against stress-induced mood and anxiety disorders. The neural circuitry underlying active coping is poorly understood, but the functioning of these circuits could be key for overcoming anxiety and related disorders. The supramammillary nucleus (SuM) has been suggested to be engaged by threat. SuM has many projections and a poorly understood diversity of neural populations. In studies using mice, we identified a unique population of glutamatergic SuM neurons (SuM::POA) based on projection to the preoptic area of the hypothalamus (POA) and found SuM::POA neurons have extensive arborizations. SuM::POA neurons project to brain areas that mediate features of the stress and threat responses including the paraventricular nucleus thalamus (PVT), periaqueductal gray (PAG), and habenula (Hb). Thus, SuM::POA neurons are positioned as a hub, connecting to areas implicated in regulating stress responses. Here we report SuM::POA neurons are recruited by diverse threatening stressors, and recruitment correlated with active coping behaviors. We found that selective photoactivation of the SuM::POA population drove aversion but not anxiety like behaviors. Activation of SuM::POA neurons in the absence of acute stressors evoked active coping like behaviors and drove instrumental behavior. Also, activation of SuM::POA neurons was sufficient to convert passive coping strategies to active behaviors during acute stress. In contrast, we found activation of GABAergic (VGAT+) SuM neurons (SuM) neurons did not alter drive aversion or active coping, but termination of photostimulation was followed by increased mobility in the forced swim test. These findings establish a new node in stress response circuitry that has projections to many brain areas and evokes flexible active coping behaviors.
Topics: Animals; Neurons; Mice; Stress, Psychological; Adaptation, Psychological; Male; Glutamic Acid; Hypothalamus, Posterior; Neural Pathways; Mice, Inbred C57BL
PubMed: 38829200
DOI: 10.7554/eLife.90972 -
Physiological Reports May 2024We have previously reported that the subfornical organ (SFO) does not contribute to the chronic hypertensive response to DOCA-salt in rats, and yet the organum...
We have previously reported that the subfornical organ (SFO) does not contribute to the chronic hypertensive response to DOCA-salt in rats, and yet the organum vasculosum of the lamina terminalis (OVLT) plays a significant role in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Since efferent fibers of the OVLT project to and through the median preoptic nucleus (MnPO), the present study was designed to test the hypothesis that the MnPO is necessary for DOCA-salt hypertension in the rat. Male Sprague-Dawley rats underwent SHAM (MnPOsham; n = 5) or electrolytic lesion of the MnPO (MnPOx; n = 7) followed by subsequent unilateral nephrectomy and telemetry instrumentation. After recovery and during the experimental protocol, rats consumed a 0.1% NaCl diet and 0.9% NaCl drinking solution. Mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg/rat; SQ). The chronic pressor response to DOCA was attenuated in MnPOx rats by Day 11 of treatment and continued such that MAP increased 25 ± 3 mmHg in MnPOsham rats by Day 21 of DOCA compared to 14 ± 3 mmHg in MnPOx rats. These results support the hypothesis that the MnPO is an important brain site of action and necessary for the full development of DOCA-salt hypertension in the rat.
Topics: Animals; Male; Rats, Sprague-Dawley; Desoxycorticosterone Acetate; Preoptic Area; Hypertension; Rats; Sodium Chloride, Dietary; Blood Pressure
PubMed: 38749925
DOI: 10.14814/phy2.16046 -
BioRxiv : the Preprint Server For... May 2024Obese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and...
Obese subjects often exhibit hypersomnia accompanied by severe sleep fragmentation, while emerging evidence suggests that poor sleep quality promotes overeating and exacerbates diet-induced obesity (DIO). However, the neural circuit and signaling mechanism underlying the reciprocal control of appetite and sleep is yet not elucidated. Here, we report a neural circuit where prokineticin receptor 2 (PROKR2)-expressing neurons within the parabrachial nucleus (PBN) of the brainstem received direct projections from neuropeptide Y receptor Y2 (NPY2R)-expressing neurons within the lateral preoptic area (LPO) of the hypothalamus. The RNA-Seq results revealed in the PBN is the most regulated GPCR signaling gene that is responsible for comorbidity of obesity and sleep dysfunction. Furthermore, those NPY2R neurons are minimally active during NREM sleep and maximally active during wakefulness and REM sleep. Activation of the NPY2R →PBN circuit or the postsynaptic PROKR2 neurons suppressed feeding of a high-fat diet and abrogated morbid sleep patterns in DIO mice. Further studies showed that genetic ablation of the PROKR2 signaling within PROKR2 neurons alleviated the hyperphagia and weight gain, and restored sleep dysfunction in DIO mice. We further discovered pterostilbene, a plant-derived stilbenoid, is a powerful anti-obesity and sleep-improving agent, robustly suppressed hyperphagia and promoted reconstruction of a healthier sleep architecture, thereby leading to significant weight loss. Collectively, our results unveil a neural mechanism for the reciprocal control of appetite and sleep, through which pterostilbene, along with a class of similarly structured compounds, may be developed as effective therapeutics for tackling obesity and sleep disorders.
PubMed: 38746393
DOI: 10.1101/2024.04.30.591948 -
Frontiers in Neural Circuits 2024The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The... (Comparative Study)
Comparative Study
The posterior intralaminar thalamic nucleus (PIL) and peripeduncular nucleus (PP) are two adjoining structures located medioventral to the medial geniculate nucleus. The PIL-PP region plays important roles in auditory fear conditioning and in social, maternal and sexual behaviors. Previous studies often lumped the PIL and PP into single entity, and therefore it is not known if they have common and/or different brain-wide connections. In this study, we investigate brain-wide efferent and afferent projections of the PIL and PP using reliable anterograde and retrograde tracing methods. Both PIL and PP project strongly to lateral, medial and anterior basomedial amygdaloid nuclei, posteroventral striatum (putamen and external globus pallidus), amygdalostriatal transition area, zona incerta, superior and inferior colliculi, and the ectorhinal cortex. However, the PP rather than the PIL send stronger projections to the hypothalamic regions such as preoptic area/nucleus, anterior hypothalamic nucleus, and ventromedial nucleus of hypothalamus. As for the afferent projections, both PIL and PP receive multimodal information from auditory (inferior colliculus, superior olivary nucleus, nucleus of lateral lemniscus, and association auditory cortex), visual (superior colliculus and ectorhinal cortex), somatosensory (gracile and cuneate nuclei), motor (external globus pallidus), and limbic (central amygdaloid nucleus, hypothalamus, and insular cortex) structures. However, the PP rather than PIL receives strong projections from the visual related structures parabigeminal nucleus and ventral lateral geniculate nucleus. Additional results from Cre-dependent viral tracing in mice have also confirmed the main results in rats. Together, the findings in this study would provide new insights into the neural circuits and functional correlation of the PIL and PP.
Topics: Animals; Rats; Mice; Male; Neural Pathways; Intralaminar Thalamic Nuclei; Mice, Inbred C57BL; Rats, Sprague-Dawley; Female
PubMed: 38736977
DOI: 10.3389/fncir.2024.1384621