Naringenin alleviates roundup-induced cytoarchitectural derangement of rat hypothalamic-pituitary-adrenal axis via modulating Sirt1/NF-κB/Nrf2 and p38-MAPK/p53 signaling pathways.

The vagus nerve activated by inflammation co-transmits acute visceral pain via the NTS-PVN pathway.

Regulation of gastrointestinal activity in response to continuous low temperature in the Daurian ground squirrel.

The ventromedial hypothalamic nucleus responds differentially to genistein exposure during development in male and female rats in the long term.

Development and evaluation of a double asymmetric spin echo planar imaging (dASE-EPI) sequence to balance sensitivity to blood oxygenation level-dependent (BOLD) contrast with mitigation of susceptibility-induced intravoxel spin dephasing in ultra high-field rodent brain imaging. A dASE-EPI pulse sequence was implemented and resting-state BOLD fMRI was acquired in the rat brain. Data acquired with dASE-EPI were compared to conventional gradient-recalled EPI. Functional connectivity analyses were performed to assess detection of established networks and to evaluate signal recovery in regions affected by susceptibility (e.g., amygdala, hypothalamic nuclei). dASE-EPI was found to provide BOLD sensitivity that was non-inferior to conventional GRE-EPI while substantially reducing susceptibility-related signal loss. Established functional networks including the bilateral insular, bilateral sensory, and default mode network were reliably detected with dASE-EPI. Functional connectivity of the amygdala, which was obscured in GRE-EPI, was recoverable with the proposed sequence. The proposed dASE-EPI pulse sequence is a viable solution when studying brain regions which suffer from severe susceptibility artifacts.

This narrative review summarizes evidence implicating a role for the hypothalamus in the prodrome phase of a migraine attack. Prodrome is the earliest phase of the migraine attack. Understanding the migraine prodrome could lead to a better description of how migraine attacks are initiated and identification of targets for acute and preventive migraine treatment. The hypothalamus has been implicated in migraine prodrome via (1) localization of common prodrome symptoms to the hypothalamus; (2) identification of neurotransmitters, peptides, and hormones important in migraine pathophysiology for which the hypothalamus influences their production or release; and (3) brain neuroimaging studies identifying changes in hypothalamic activity and functional connectivity during the prodrome and preheadache phases of the migraine attack. For this narrative review, PubMed was searched for relevant English language articles using the terms "hypothalamus, prodrome," "hypothalamus, premonitory," "hypothalamus, migraine," "migraine, prodrome," and "migraine, premonitory." The PubMed search was performed on October 29, 2025. Full articles were chosen for review based on their relevance to the three areas defined just above: symptom localization, neuropeptide/neurotransmitter release, and brain imaging. Those with migraine commonly, and often consistently, experience prodrome symptoms, including hypersensitivities to visual and auditory stimuli, neck pain, fatigue, sleep-wake disturbances, changes in appetite, mood changes, and alterations in thermoregulation perception. Many of these symptoms can be localized to functions of hypothalamic subregions and nuclei. Several neuropeptides, neurotransmitters, and hormones that contribute to prodrome and other migraine attack symptoms, including calcitonin gene-related peptide, dopamine, orexins, and pituitary adenylate cyclase-activating polypeptide, are either produced by the hypothalamus or their release is mediated by the hypothalamus. Functional neuroimaging studies of spontaneous and triggered migraine attacks have identified increased hypothalamic activity and altered hypothalamic functional connectivity before migraine headache onset, including during the prodrome. There is compelling evidence that the hypothalamus plays a role in the migraine prodrome and likely in migraine attack initiation. This is supported by many migraine prodrome symptoms localizing to hypothalamic function and functional neuroimaging studies demonstrating increased activity and altered connectivity of the hypothalamus during the prodrome phase. Further evidence and research are required to understand the hypothalamus' contribution relative to other brain regions.

The selection of the appropriate energy substrate under different physiological conditions is a key aspect of the energy metabolism homeostasis. We here show that Nos1 (nitric oxide synthase 1)-expressing cells in the paraventricular hypothalamic nucleus (PVH) serve as a pivotal node for controlling whole-body fat consumption in male mice. Nos1 neurons account for ~30% of PVH neurons that convey signals via polysynaptic pathways to individual peripheral tissues, including skeletal muscle and brown (BAT) and white (WAT) adipose tissues. Activation of these Nos1 neurons in the PVH area induces WAT lipolysis and fat oxidation in other peripheral tissues via the sympathetic nervous system, thereby increasing whole-body fat consumption. Inhibition of these neurons abolishes the increase in fat consumption during the light period, whereas long-term silencing lead to obesity independent of energy intake. These neurons are also necessary for cold-induced thermogenesis in BAT and the rapid increase in fat consumption elicited by food deprivation or other stressors. Nos1 neurons in the PVH area are therefore essential for controlling fat consumption and energy homeostasis.

Hypertension increases the risk for cardiovascular and cerebrovascular diseases and both its preventive and current therapeutics measures require extensive investigations. Despite that Gastrodin, a neuroprotective compound extracted from a Traditional Chinese medicine (TCM), reportedly has preventive and curative potentials in hypertensive patients, its molecular mechanisms in lowering blood pressure still remain obscure. This study was designed to test the hypothesis that gastrodin lowers blood pressure by targeting the PPAR-γ/NF-κB/NLRP3 signaling axis in the hypothalamic paraventricular (PVN). Gastrodin or vehicle (artificial cerebrospinal fluid, aCSF) was directly infused into the PVN through a mini osmotic pump for 28 days to Spontaneous hypertensive rats (SHRs) and Wistar Kyoto (WKY). Four groups of rats were set: WKY + PVN vehicle; WKY + PVN Gastrodin; SHR + PVN vehicle; and SHR + PVN Gastrodin. Blood pressure was monitored and at the conclusion of experiment, plasma and PVN samples were collected and processed for ELISA, PCR, Western blotting and Immunofluorescence analyses. SHRs had elevated blood pressure (BP), heart rate (HR) and plasmatic norepinephrine (NE) validating their hypertensive status. PVN micro-infusion of gastrodin markedly reversed these hypertensive features in SHRs. At molecular level, gastrodin attenuated the local production of reactive oxygen species (ROS), reduced NADPH Oxidases (NOX)2 and NOX4 messenger RNA (mRNA) level and attenuated the activation of PPAR-γ in the PVN. In addition, gastrodin reduced the inflammasome activation and the expression of interleukin-1β (IL-1β). Furthermore, pretreatment with gastrodin reduced the expression of caspase-1 p10 and inflammation (IL-1β and MCP-1), the ratio of phosphorylated kappa B kinase (p-IKK)/IKK, and that of p-p65/p65 in the PVN of SHRs. In conclusion, gastrodin-lowered blood pressure is associated with balanced PPAR-γ/NF-κB/NLRP3 signaling axis within the PVN local highlighting its promising properties in the management of hypertension.

Protein tyrosine phosphatase δ (PTPδ) is involved in Sema3A-induced dendritic elaboration of cortical pyramidal neurons through the activation of Fyn tyrosine kinase. However, the in vivo substrates of PTPδ remain largely unknown. Phosphotyrosine proteome analysis of Ptpδ -/- mice brains from both male and female revealed that signal regulatory protein α (SIRPα) was hyperphosphorylated at the carboxy-terminal Tyr501 residue in the knock-outs. Immunohistochemistry with anti-phospho-Tyr501 SIRPα antibody showed the hyperphosphorylation of SIRPα in various regions including the olfactory nerve layer, cortex, striatum, thalamic reticular, and hypothalamic nuclei in Ptpδ-/- brain sections. These regions partially correlated with PTPδ expression. In the primary cultured wild-type (wt) mouse dorsal root ganglion neurons, Sirpα knockdown or overexpression of a cytoplasmic deleted SIRPα mutant partially blocked the Sema3A-induced growth cone collapse response. However, overexpression of nonphosphorylated mutants of SIRPα did not alter the response. This suggests that SIRPα is involved in the Sema3A-induced collapse response in an independent manner of phosphorylation and/or dephosphorylation. In the primary cultured cortical neurons, Sirpα knockdown or the overexpression of SIRPα-Tyr501Phe mutant attenuated Sema3A-induced dendritic growth. In cultured Sirpα -/- cortical neurons, re-expression of wt SIRPα, but not of SIRPα-Tyr501Phe, restored Sema3A-induced dendritic formation. In vivo analyses revealed ectopic expression of SIRPα-Tyr501Phe in cortical layer II/III pyramidal neurons with misoriented apical dendrites and attenuated basal dendrite arborization. Similar irregular cortical dendrites were observed in Sirpα -/- and Ptpδ -/- brains. Collectively, our results demonstrate that PTPδ regulates the dendritic elaboration of cortical pyramidal neurons through the dephosphorylation of SIRPα.

Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility.

Appetite regulation is a complex yet vital concept, with several pathways conserved throughout evolution that are still to be fully understood. Appetite, or the drive to search for and consume food, is driven by the integration of different food and environmental cues, as well as internal state. It is dynamically managed by intricate systems that can be broadly categorized into homeostatic (driven by physiological energy needs) and hedonic feeding (driven by pleasure and reward). This review compiles and analyzes recently described and unconventional mechanisms of appetite control in mammals, detailing their underlying molecular pathways and neural circuit integration, and implications for drug discovery. The hypothalamus plays a vital role in this, serving as the main hub for appetite control, integrating peripheral hormonal and neural signals to maintain energy balance and where several pathways converge. Beyond the established hypothalamic Arcuate Nucleus (ARC) circuit, key regulators examined include neuropeptides like Orexin A, Oxyntomodulin, PACAP, and Galanin, alongside key receptor systems such as the Melanocortin-3 receptor (MC3R), the Endocannabinoid (ECS) and the Endorphin Systems. We also explore the roles of the NUCB2/nesfatin-1 pathway and amino acid transporters (SLCs). These examinations resulted in a blurred vision of the distinction between homeostatic and hedonic regulation, with pathways converging on the hypothalamus as well as the mesolimbic reward system. Understanding this interconnected regulatory network is vital for improving therapies for disorders such as obesity, anorexia nervosa, and binge-eating disorder. This comprehensive knowledge paves the way for the development of targeted, precision medicine, or the implementation of multi-target compounds.

Chemogenetic activation of the amygdala core nucleus increases aggression in chickens

Central insulin action in the brain is thought to contribute to metabolic regulation, but the specific hypothalamic nuclei affected in type 2 diabetes (T2D) remain poorly characterized. We performed high-resolution functional MRI (fMRI) during intranasal insulin administration to assess nucleus-level hypothalamic responses in 21 Japanese men with T2D and 20 individuals acting as healthy controls. In controls, insulin rapidly suppressed fMRI signals within 5 minutes in the posterior hypothalamic nucleus; this early suppression was not observed in T2D, indicating impaired hypothalamic insulin responsiveness. In an independent older cohort, structural MRI further revealed decreased gray matter volume in the corresponding posterior hypothalamus in participants with diabetes. These converging functional and structural findings implicate the posterior hypothalamus as a candidate locus associated with brain insulin resistance in T2D, warranting longitudinal and interventional validation.

Heightened sympathetic outflow is a major contributor to the development of hypertension. The hypothalamic paraventricular nucleus (PVN) and the rostral ventrolateral medulla (RVLM) are critical regions for generating and regulating sympathetic activity associated with hypertension. Although presympathetic neural circuitry in the healthy brain is well characterized, it remains unclear whether these pathways undergo alterations in hypertension. Here, we determined presympathetic neural circuits by injecting pseudorabies virus (PRV), a transsynaptic retrograde tracer, into the adrenal gland of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Adult SHR exhibited a significantly greater number of PRV-labeled neurons in the PVN and RVLM, but not in the spinal intermediolateral column, compared with WKY. In contrast, the numbers of PRV-labeled neurons in the PVN and RVLM were comparable between young, prehypertensive SHR and age-matched WKY. Remarkably, long-term treatment with losartan—a brain-penetrant angiotensin II AT1 receptor antagonist— initiated in young, prehypertensive SHR blunted the age-dependent hypertension development and reversed the increase in neuronal labeling in both the PVN and RVLM. However, losartan treatment had no effects in WKY. Additionally, electrophysiological recordings showed an elevated frequency of miniature excitatory postsynaptic currents in PVN presympathetic neurons of SHR, which was also normalized by long-term losartan treatment. These findings reveal an age-dependent expansion of presympathetic neuronal connectivity from the hypothalamus and brainstem to the adrenal gland during hypertension development in SHR. Enhanced AT1 receptor activity contributes to hypertension by increasing active glutamatergic synaptic input and promoting the recruitment of additional presympathetic neurons in the hypothalamus and brainstem.Key Points1. The numbers of neurons labeled by PRV injected into the adrenal gland are increased in the PVN and RVLM, but not in the spinal cord IML, in adult SHR compared to normotensive WKY. 2. The numbers of neurons in the PVN, RVLM, and spinal cord labeled by PRV injected into the adrenal gland are comparable in young, prehypertensive SHR and age-matched WKY. 3. Losartan treatment, initiated at a young age, blunts the hypertension development and reverses the increased numbers of PRV-labeled neurons in the PVN and RVLM of adult SHR but has no such effects in WKY. 4. The active glutamatergic synapses in PVN presympathetic neurons are elevated in adult SHR, and this elevation is reversed by long-term losartan treatment.

Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells.

ABSTRACTAstrocytes actively contribute to sleep regulation through intracellular calcium (Ca2+) signaling. Yet, whether astrocytic dynamics within sleep‐promoting hypothalamic nuclei vary across the nycthemeral cycle in a sex‐dependent manner remains unknown. The ventrolateral preoptic area (VLPO) is a key sleep‐promoting nucleus whose neuronal circuitry has been extensively characterized. However, the local astrocytic Ca2+ activity remains poorly defined. Here, we investigated astrocytic Ca2+ signaling in the VLPO of male and female mice across the nycthemeral cycle. Using two‐photon Ca2+ imaging in acute VLPO‐containing brain slices prepared at Zeitgeber Time (ZT)‐2, corresponding to the onset of the rest period, and ZT‐14, corresponding to the beginning of the active period, we combined single‐event analyses with graph‐based network approaches to characterize astrocytic activity across scales. At the level of individual events, spontaneous astrocytic Ca2+ dynamics exhibited marked state dependence and sexual dimorphism. In males, Ca2+ events were smaller and faster at ZT‐14 than at ZT‐2 (shorter duration and accelerated rise and decay time). In contrast, in females, ZT‐14 was characterized by increased event amplitude and frequency, consistent with upregulated Ca2+ signaling during the active phase. At the network level, functional connectivity remained stable in males. Conversely, females exhibited robust network remodeling at ZT‐14, including increased astrocyte recruitment, higher node degree of correlations, and a marked rise in the number and proportion of highly connected astrocytes. Together, these findings reveal sex‐specific astrocytic signaling strategies in the VLPO across the nycthemeral cycle and underscore the need to incorporate sex as a biological variable in astrocyte‐based sleep research.

Angiotensin II Receptor Signaling in the Hypothalamic-Pituitary-Adrenal Axis and Spleen After Spinal Cord Injury Depends on the Sympathetic Innervation Integrity.

3037-LB: Androgen Receptor Action in Arcuate Nucleus Impairs Estrogen Insulin-Sensitizing Actions and Insulin Suppression of Hepatic Glucose Production in Female Mice

Posterior hypothalamic nucleus serotonin depletion facilitates spatial learning and increases power and coherence in the posterior hypothalamic-septal-hippocampal circuit in rat.

To elucidate the central mechanism of pituitary-derived prolactin (PRL) in hepatic lipid homeostasis and identify therapeutic targets for metabolic dysfunction-associated fatty liver disease (MASLD). High-fat diet (HFD)-fed mice induced MASLD. PRL⁻/⁻ mice, POMC neuron-specific PRL receptor (PRLR) conditional knockout mice, AAV-mediated PRLR knockdown, and central/peripheral PRL administration were used to explore PRL's central regulatory role. Metabolic phenotyping, histological/biochemical assays, immunofluorescence, electrophysiology, RNA-seq, 6-OHDA-induced sympathetic denervation, and primary hepatocyte experiments were performed to evaluate phenotypes, neuronal activity and underlying mechanisms. PRL deficiency exacerbated HFD-induced hepatic lipid deposition, and central intracerebroventricular PRL alleviated hepatic steatosis in HFD-fed PRL⁻/⁻ and wild-type mice more rapidly than peripheral intraperitoneal PRL. PRLR was highly expressed in hypothalamic arcuate nucleus POMC neurons, which PRL selectively activated by enhancing neuronal excitability. POMC-specific PRLR knockout abrogated PRL's anti-steatotic effects and aggravated HFD-induced hepatic lipid accumulation. Mechanistically, central PRL enhanced hepatic sympathetic outflow to suppress de novo lipogenesis via the FASN pathway. PRL acts on hypothalamic POMC neurons to enhance hepatic sympathetic activity, suppressing FASN-mediated lipogenesis and maintaining lipid homeostasis. This novel PRL-driven brain-liver circuit highlights central PRL signaling as a promising MASLD therapeutic target.