RESUMEN

A previous study on ovarian and hypothalami transcriptome analysis in white Muscovy duck revealed that MAP3K8 gene participated in MAPK signaling pathway that influence egg production. Additionally, MAP3K8 was predicted as a target gene of miRNA-509-3p that promotes the secretion of oestradiol which is an important hormone in egg ovulation. This suggested that MAP3K8 might have a functional role in the reproductive performance "egg production" of white Muscovy ducks. Herein, we focused on expression level of MAP3K8 in reproductive and non-reproductive tissues of highest (HP) and lowest (LP) egg producing white Muscovy ducks and identified the polymorphism in MAP3K8 and its association with three egg production traits; Age at first egg (AFE), number of eggs at 300 days (N300D) and 59 weeks (N59W). The results of expression level indicated that mRNA of MAP3K8 was significantly (p < 0.01) expressed in the oviduct than in the ovary and hypothalamus. Seven synonymous SNPs were detected, and association analysis showed that g.148303340 G>A and g.148290065 A>G were significantly (p < 0.05) associated with N300D and N59W. The results of this study might serve as molecular marker for marker-assisted selection of white Muscovy ducks for egg production.

Asunto(s)

Patos , Perfilación de la Expresión Génica , Quinasas Quinasa Quinasa PAM , Ovario , Polimorfismo de Nucleótido Simple , Animales , Patos/genética , Femenino , Ovario/metabolismo , Quinasas Quinasa Quinasa PAM/genética , Quinasas Quinasa Quinasa PAM/metabolismo , Hipotálamo/metabolismo , Oviductos/metabolismo

RESUMEN

Context Understanding of central nervous system mechanisms related to age-related infertility remains limited. Fibril α-synuclein, distinct from its monomer form, is implicated in age-related diseases and propagates among neurons akin to prions. Aims We compared α-synuclein expression in gonadotropin-releasing hormone-expressing neurons (GnRH neurons) in the pre-optic area, arcuate nucleus, and median eminence of healthy heifers and aged cows to determine its role in age-related infertility. Methods We analysed mRNA and protein expression, along with fluorescent immunohistochemistry for GnRH and α-synuclein, followed by Congo red staining to detect amyloid deposits, and confocal microscopy. Key results Both mRNA and protein expressions of α-synuclein were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and western blots in bovine cortex, hippocampus, and anterior and posterior hypothalamus tissues. Significant differences in α-synuclein mRNA expression were observed in the cortex and hippocampus between young and old cows. Western blots showed five bands of α-synuclein, probably reflecting monomer, dimer, and oligomers, in the cortex, hippocampus, hypothalamus tissues, and there were significant differences in some bands between young and old cows. Bright-field and polarised light microscopy did not detect obvious amyloid deposition in aged hypothalami; however, higher-sensitive confocal microscopy unveiled strong positive signal of Congo red and α-synuclein in GnRH neurons in aged hypothalami. Additionally, α-synuclein expression was detected in immortalised GnRH neurons, GT1-7 cells. Conclusion Alpha-synuclein was expressed in GnRH neurons, and some differences were observed between young and old hypothalami. Implications Alpha-synuclein may play an important role in aging-related infertility.

Asunto(s)

Envejecimiento , Hormona Liberadora de Gonadotropina , Hipotálamo , Neuronas , alfa-Sinucleína , Animales , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/genética , Bovinos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Neuronas/metabolismo , Hipotálamo/metabolismo , Femenino , Envejecimiento/metabolismo , ARN Mensajero/metabolismo

RESUMEN

Systemic inflammation elicits sickness behaviors and fever by engaging a complex neuronal circuitry that begins in the preoptic area of the hypothalamus. Ectotherms such as teleost fish display sickness behaviors in response to infection or inflammation, seeking warmer temperatures to enhance survival via behavioral fever responses. To date, the hypothalamus is the only brain region implicated in sickness behaviors and behavioral fever in teleosts. Yet, the complexity of neurobehavioral manifestations underlying sickness responses in teleosts suggests engagement of higher processing areas of the brain. Using in vivo models of systemic inflammation in rainbow trout, we find canonical pyrogenic cytokine responses in the hypothalamus whereas in the telencephalon and the optic tectum il-1b and tnfa expression is decoupled from il-6 expression. Polyamine metabolism changes, characterized by accumulation of putrescine and decreases in spermine and spermidine, are recorded in the telencephalon but not hypothalamus upon systemic injection of bacteria. While systemic inflammation causes canonical behavioral fever in trout, blockade of bacterial polyamine metabolism prior to injection abrogates behavioral fever, polyamine responses, and telencephalic but not hypothalamic cytokine responses. Combined, our work identifies the telencephalon as a neuronal substrate for brain responses to systemic inflammation in teleosts and uncovers the role of polyamines as critical chemical mediators in sickness behaviors.

Asunto(s)

Inflamación , Oncorhynchus mykiss , Poliaminas , Telencéfalo , Animales , Telencéfalo/metabolismo , Poliaminas/metabolismo , Inflamación/metabolismo , Oncorhynchus mykiss/metabolismo , Oncorhynchus mykiss/inmunología , Neuronas/metabolismo , Hipotálamo/metabolismo , Espermina/metabolismo , Putrescina/metabolismo , Conducta de Enfermedad/fisiología , Espermidina/metabolismo

RESUMEN

The central nervous system has been implicated in the age-induced reduction in adipose tissue lipolysis. However, the underlying mechanisms remain unclear. Here, we show the expression of SLC7A14 is reduced in proopiomelanocortin (POMC) neurons of aged mice. Overexpression of SLC7A14 in POMC neurons alleviates the aging-reduced lipolysis, whereas SLC7A14 deletion mimics the age-induced lipolysis impairment. Metabolomics analysis reveals that POMC SLC7A14 increased taurochenodeoxycholic acid (TCDCA) content, which mediates the SLC7A14 knockout- or age-induced WAT lipolysis impairment. Furthermore, SLC7A14-increased TCDCA content is dependent on intestinal apical sodium-dependent bile acid transporter (ASBT), which is regulated by intestinal sympathetic afferent nerves. Finally, SLC7A14 regulates the intestinal sympathetic afferent nerves by inhibiting mTORC1 signaling through inhibiting TSC1 phosphorylation. Collectively, our study suggests the function for central SLC7A14 and an upstream mechanism for the mTORC1 signaling pathway. Moreover, our data provides insights into the brain-gut-adipose tissue crosstalk in age-induced lipolysis impairment.

Asunto(s)

Tejido Adiposo Blanco , Envejecimiento , Sistema de Transporte de Aminoácidos y+ , Hipotálamo , Lipólisis , Animales , Masculino , Ratones , Tejido Adiposo Blanco/metabolismo , Envejecimiento/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Hipotálamo/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Neuronas/metabolismo , Proopiomelanocortina/metabolismo , Proopiomelanocortina/genética , Transducción de Señal , Simportadores/metabolismo , Simportadores/genética

RESUMEN

BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent sleep disorder that is associated with structural brain damage and cognitive impairment. The hypothalamus plays a crucial role in regulating sleep and wakefulness. We aimed to evaluate hypothalamic subunit volumes in patients with OSA. METHODS: We enrolled 30 participants (15 patients with OSA and 15 healthy controls (HC)). Patients with OSA underwent complete overnight polysomnography (PSG) examination. All the participants underwent MRI. The hypothalamic subunit volumes were calculated using a segmentation technique that trained a 3D convolutional neural network. RESULTS: Although hypothalamus subunit volumes were comparable between the HC and OSA groups (lowest p = .395), significant negative correlations were found in OSA patients between BMI and whole left hypothalamus volume (R = -0.654, p = .008), as well as between BMI and left posterior volume (R = -0.556, p = .032). Furthermore, significant positive correlations were found between ESS and right anterior inferior volume (R = 0.548, p = .042), minimum SpO2 and the whole left hypothalamus (R = 0.551, p = .033), left tubular inferior volumes (R = 0.596, p = .019), and between the percentage of REM stage and left anterior inferior volume (R = 0.584, p = .022). CONCLUSIONS: While there were no notable differences in the hypothalamic subunit volumes between the OSA and HC groups, several important correlations were identified in the OSA group. These relationships suggest that factors related to sleep apnea severity could affect hypothalamic structure in patients.

Asunto(s)

Hipotálamo , Imagen por Resonancia Magnética , Polisomnografía , Apnea Obstructiva del Sueño , Humanos , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/diagnóstico por imagen , Masculino , Hipotálamo/diagnóstico por imagen , Hipotálamo/fisiopatología , Persona de Mediana Edad , Adulto , Femenino

RESUMEN

To ensure survival, animals must sometimes suppress fear responses triggered by potential threats during feeding. However, the mechanisms underlying this process remain poorly understood. In the current study, we demonstrated that when fear-conditioned stimuli (CS) were presented during food consumption, a neural projection from lateral hypothalamic (LH) GAD2 neurons to nucleus incertus (NI) relaxin-3 (RLN3)-expressing neurons was activated, leading to a reduction in CS-induced freezing behavior in male mice. LHGAD2 neurons established excitatory connections with the NI. The activity of this neural circuit, including NIRLN3 neurons, attenuated CS-induced freezing responses during food consumption. Additionally, the lateral mammillary nucleus (LM), which received NIRLN3 projections, along with RLN3 signaling in the LM, mediated the decrease in freezing behavior. Collectively, this study identified an LHGAD2-NIRLN3-LM circuit involved in modulating fear responses during feeding, thereby enhancing our understanding of how animals coordinate nutrient intake with threat avoidance.

Asunto(s)

Miedo , Animales , Miedo/fisiología , Masculino , Ratones , Hipotálamo/fisiología , Hipotálamo/metabolismo , Relaxina/metabolismo , Neuronas/fisiología , Neuronas/metabolismo , Ratones Endogámicos C57BL , Vías Nerviosas/fisiología , Ingestión de Alimentos/fisiología , Condicionamiento Clásico/fisiología , Área Hipotalámica Lateral/fisiología , Área Hipotalámica Lateral/metabolismo

RESUMEN

Kynurenic acid (KYNA), a tryptophan metabolite, is believed to exert neuromodulatory and neuroprotective effects in the brain. This study aimed to examine KYNA's capacity to modify gene expression and the activity of cellular antioxidant enzymes in specific structures of the sheep brain. Anestrous sheep were infused intracerebroventricularly with two KYNA doses-lower (4 × 5 µg/60 µL/30 min, KYNA20) and higher (4 × 25 µg/60 µL/30 min, KYNA100)-at 30 min intervals. The abundance of superoxide dismutase 2 (SOD2), catalase (CAT), and glutathione peroxidase 1 (GPx1) mRNA, as well as enzyme activities, were determined in the medial-basal hypothalamus (MBH), the preoptic (POA) area of the hypothalamus, and in the hippocampal CA1 field. Both doses of KYNA caused a decrease (p < 0.01) in the expression of SOD2 and CAT mRNA in all structures examined compared to the control group (except for CAT in the POA at the KYNA100 dose). Furthermore, lower levels of SOD2 mRNA (p < 0.05) and CAT mRNA (p < 0.01) were found in the MBH and POA and in the POA and CA, respectively, in sheep administered with the KYNA20 dose. Different stimulatory effects on GPx1 mRNA expression were observed for both doses (p < 0.05-p < 0.01). KYNA exerted stimulatory but dose-dependent effects on SOD2, CAT, and GPx1 activities (p < 0.05-p < 0.001) in all brain tissues examined. The results indicate that KYNA may influence the level of oxidative stress in individual brain structures in sheep by modulating the expression of genes and the activity of at least SOD2, CAT, and GPx1. The present findings also expand the general knowledge about the potential neuroprotective properties of KYNA in the central nervous system.

Asunto(s)

Antioxidantes , Catalasa , Glutatión Peroxidasa GPX1 , Glutatión Peroxidasa , Hipocampo , Hipotálamo , Ácido Quinurénico , Superóxido Dismutasa , Animales , Ovinos , Ácido Quinurénico/metabolismo , Ácido Quinurénico/farmacología , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Catalasa/metabolismo , Catalasa/genética , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Antioxidantes/metabolismo , Antioxidantes/farmacología , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Regulación de la Expresión Génica/efectos de los fármacos , Femenino

RESUMEN

OBJECTIVE: Glucagon-like peptide-1 (GLP1) and leptin (Lep) are afferent signals that regulate energy metabolism. Lactational hypernutrition results in hyperphagia and adiposity in adult life, and these events can be prevented by exercise. We evaluated the effects of swimming training on hypothalamic (GLP1-R) and Lep receptor (Lep-R) gene expressions in lactational hypernutrition-induced obesity. METHODS: On the 3rd postnatal day, the litter sizes of lactating dams were adjusted to small litters (SL; 3 pups/dams) or normal litters (NL; 9 pups/dams). After weaning (21 days), NL and SL male rats were randomly distributed to sedentary (Sed) and exercised (Exe) groups. Exercised mice swam (30 min/3 times/week) for 68 days. Food intake and body weight gain were registered. At 92 days, intraperitoneal glucose and insulin tolerance tests were performed and rats were euthanized at 93 days; adipose tissue depots were weighed, and blood counts and plasma biochemical analyses performed. Hypothalamus were isolated to evaluate Lep-R and GLP1-R gene expressions. RESULTS: Small litters sedentary rats presented increased body weight gain, adiposity, insulin sensibility and higher fasting values of glucose and triglycerides, besides higher hypothalamic gene expressions of Lep-R and GLP1-R, compared to NLSed animals. SLExe rats did not develop obesity or metabolic abnormalities and Lep-R and GLP1-R hypothalamic gene expressions were normalized. CONCLUSION: Lactational hypernutrition induces obesity and metabolic dysfunction in adult life, in association with higher hypothalamic expressions of the Lep-R and GLP1-R genes. Exercise prevented obesity and improved metabolic state in SL overnourished rats, and normalized their hypothalamic Lep-R and GLP1-R gene expressions.

Asunto(s)

Hipotálamo , Obesidad , Condicionamiento Físico Animal , Ratas Wistar , Receptores de Leptina , Natación , Animales , Hipotálamo/metabolismo , Obesidad/metabolismo , Obesidad/genética , Obesidad/prevención & control , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Masculino , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Femenino , Natación/fisiología , Tamaño de la Camada , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/genética , Ratas , Lactancia/metabolismo , Lactancia/fisiología , Péptido 1 Similar al Glucagón/metabolismo , Leptina/sangre , Leptina/metabolismo , Distribución Aleatoria , Expresión Génica , Ingestión de Alimentos/fisiología , Adiposidad/fisiología

RESUMEN

There has been an alarming trend toward earlier puberty in girls, suggesting the influence of an environmental factor(s). As the reactivation of the reproductive axis during puberty is thought to be mediated by the hypothalamic neuropeptides kisspeptin and gonadotropin-releasing hormone (GnRH), we asked whether an environmental compound might activate the kisspeptin (KISS1R) or GnRH receptor (GnRHR). We used GnRHR or KISS1R-expressing HEK293 cells to screen the Tox21 10K compound library, a compendium of pharmaceuticals and environmental compounds, for GnRHR and KISS1R activation. Agonists were identified using Ca2+ flux and phosphorylated extracellularly regulated kinase (p-ERK) detection assays. Follow-up studies included measurement of genes known to be upregulated upon receptor activation using relevant murine or human cell lines and molecular docking simulation. Musk ambrette was identified as a KISS1R agonist, and treatment with musk ambrette led to increased expression of Gnrh1 in murine and human hypothalamic cells and expansion of GnRH neuronal area in developing zebrafish larvae. Molecular docking demonstrated that musk ambrette interacts with the His309, Gln122, and Gln123 residues of the KISS1R. A group of cholinergic agonists with structures similar to methacholine was identified as GnRHR agonists. When applied to murine gonadotrope cells, these agonists upregulated Fos, Jun, and/or Egr1. Molecular docking revealed a potential interaction between GnRHR and 5 agonists, with Asn305 constituting the most conservative GnRHR binding site. In summary, using a Tox21 10K compound library screen combined with cellular, molecular, and structural biology techniques, we have identified novel environmental agents that may activate the human KISS1R or GnRHR.

Asunto(s)

Receptores de Kisspeptina-1 , Receptores LHRH , Humanos , Femenino , Animales , Receptores de Kisspeptina-1/metabolismo , Receptores de Kisspeptina-1/genética , Receptores LHRH/metabolismo , Receptores LHRH/genética , Ratones , Células HEK293 , Pez Cebra , Hormona Liberadora de Gonadotropina/metabolismo , Pubertad/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Simulación del Acoplamiento Molecular , Maduración Sexual/efectos de los fármacos , Maduración Sexual/fisiología , Kisspeptinas/metabolismo , Kisspeptinas/genética , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/farmacología

RESUMEN

This study hypothesized that SCFA, acetate impacts positively on hypothalamic pyroptosis and its related abnormalities in experimentally induced PCOS rat model, possibly through NrF2/HIF1-α modulation. Eight-week-old female Wister rats were divided into groups (n = 5), namely control, PCOS, acetate and PCOS + acetate groups. Induction of PCOS was performed by administering 1 mg/kg body weight of letrozole for 21 days. After PCOS confirmation, the animals were treated with 200 mg/kg of acetate for 6 weeks. Rats with PCOS were characterized with insulin resistance, leptin resistance, increased plasma testosterone as well as degenerated ovarian follicles. There was also a significant increase in hypothalamic triglyceride level, triglyceride-glucose index, inflammatory biomarkers (SDF-1 and NF-kB) and caspase-6 as well as plasma LH and triglyceride. A decrease was observed in plasma adiponectin, GnRH, FSH, and hypothalamic GABA with severe inflammasome expression in PCOS rats. These were accompanied by decreased level of NrF2/HIF1-α, and the alterations were reversed when treated with acetate. Collectively, the present results suggest the therapeutic impact of acetate on hypothalamic pyroptosis and its related comorbidity in PCOS, a beneficial effect that is accompanied by modulation of NrF2/HIF1-α.

Asunto(s)

Hipotálamo , Subunidad alfa del Factor 1 Inducible por Hipoxia , Síndrome del Ovario Poliquístico , Piroptosis , Ratas Wistar , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/patología , Femenino , Animales , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Hipotálamo/patología , Piroptosis/efectos de los fármacos , Ratas , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Resistencia a la Insulina , Factor 2 Relacionado con NF-E2/metabolismo , Modelos Animales de Enfermedad , Letrozol/farmacología , Triglicéridos/sangre , Triglicéridos/metabolismo , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/sangre , Adiponectina/metabolismo , Adiponectina/sangre , Testosterona/sangre , Leptina/sangre , Leptina/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Ácido gamma-Aminobutírico/metabolismo

RESUMEN

BACKGROUND: Exploring the physiological and molecular mechanisms underlying goat sexual maturation can enhance breeding practices and optimize reproductive efficiency and is therefore substantially important for practical breeding purposes. As an essential neuroendocrine organ in animals, the hypothalamus is involved in sexual development and other reproductive processes in female animals. Although microRNAs (miRNAs) have been identified as significant regulators of goat reproduction, there is a lack of research on the molecular regulatory mechanisms of hypothalamic miRNAs that are involved in the sexual development of goats. Therefore, we examined the dynamic changes in serum hormone profiles and hypothalamic miRNA expression profiles at four developmental stages (1 day (neonatal, D1, n = 5), 2 months (prepubertal, M2, n = 5), 4 months (sexual maturity, M4, n = 5), and 6 months (breeding period, M6, n = 5)) during sexual development in Jining grey goats. RESULTS: Transcriptome analysis revealed 95 differentially expressed miRNAs (DEMs) in the hypothalamus of goats across the four developmental stages. The target genes of these miRNAs were significantly enriched in the GnRH signalling pathway, the PI3K-Akt signalling pathway, and the Ras signalling pathway (P < 0.05). Additionally, 16 DEMs are common among the M2 vs. D1, M4 vs. D1, and M6 vs. D1 comparisons, indicating that the transition from D1 to M2 represents a potentially critical period for sexual development in Jining grey goats. The bioinformatics analysis results indicate that miR-193a/miR-193b-3p-Annexin A7 (ANXA7), miR-324-5p-Adhesion G protein-coupled receptor A1 (ADGRA1), miR-324-3p-Erbb2 receptor tyrosine kinase 2 (ERBB2), and miR-324-3p-Rap guanine nucleotide exchange factor 3 (RAPGEF3) are potentially involved in biological processes such as hormone secretion, energy metabolism, and signal transduction. In addition, we further confirmed that miR-324-3p targets the regulatory gene RAPGEF3. CONCLUSION: These results further enrich the expression profile of hypothalamic miRNAs in goats and provide important insights for studying the regulatory effects of hypothalamic miRNAs on the sexual development of goats after birth.

Asunto(s)

Perfilación de la Expresión Génica , Cabras , Hipotálamo , MicroARNs , Animales , Cabras/genética , Cabras/metabolismo , Hipotálamo/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Masculino , Transcriptoma , Desarrollo Sexual/genética , Transducción de Señal , Regulación del Desarrollo de la Expresión Génica , Maduración Sexual/genética

RESUMEN

Multiple organs orchestrate the maintenance of proper physiological function in organisms throughout their lifetimes. Recent studies have uncovered that aging and longevity are regulated by cell non-autonomous signaling mechanisms in several organisms. In the brain, particularly in the hypothalamus, aging and longevity are regulated by such cell non-autonomous signaling mechanisms. Several hypothalamic neurons have been identified as regulators of mammalian longevity, and manipulating them promotes lifespan extension or shortens the lifespan in rodent models. The hypothalamic structure and function are evolutionally highly conserved across species. Thus, elucidation of hypothalamic function during the aging process will shed some light on the mechanisms of aging and longevity and, thereby benefiting to human health.

Asunto(s)

Envejecimiento , Longevidad , Transducción de Señal , Animales , Longevidad/fisiología , Envejecimiento/fisiología , Transducción de Señal/fisiología , Humanos , Sistema Nervioso Central/fisiología , Mamíferos/fisiología , Hipotálamo/fisiología , Hipotálamo/metabolismo , Neuronas/fisiología

RESUMEN

The hypothalamus receives serotonergic projections from the raphe nucleus in a sex-specific manner. During systemic inflammation, hypothalamic levels of serotonin (5-hydroxytryptamine [5-HT]) decrease in male rats. The present study evaluated the involvement of endothelin-1 (ET-1) in the febrile response, hypolocomotion, and changes in hypothalamic 5-HT levels during systemic inflammation in male and female rats. An intraperitoneal injection of lipopolysaccharide (LPS) induced a febrile response and hypolocomotion in both male and female rats. However, although LPS reduced hypothalamic levels of 5-HT and its metabolite 5-hydroxyindol acetic acid (5-HIAA) in male rats, it increased these levels in female rats. An intracerebroventricular injection of the endothelin-B receptor antagonist BQ788 significantly reduced LPS-induced fever and hypolocomotion and changes in hypothalamic 5-HT and 5-HIAA levels in both male and female rats. The i.c.v. administration of ET-1 induced a significant fever and hypolocomotion, but reduced the hypothalamic levels of 5-HT and 5-HIAA in both males and females. These results suggest an important sexual dimorphism during systemic inflammation regarding the release of 5-HT in the hypothalamus. Moreover, ET-1 arises as an important mediator involved in the changes in hypothalamic 5-HT levels in both male and female rats.

Asunto(s)

Endotelina-1 , Hipotálamo , Inflamación , Piperidinas , Ratas Wistar , Serotonina , Caracteres Sexuales , Animales , Masculino , Femenino , Endotelina-1/metabolismo , Hipotálamo/metabolismo , Hipotálamo/efectos de los fármacos , Ratas , Inflamación/metabolismo , Inflamación/inducido químicamente , Serotonina/metabolismo , Piperidinas/farmacología , Lipopolisacáridos/toxicidad , Oligopéptidos/farmacología , Ácido Hidroxiindolacético/metabolismo , Antagonistas de los Receptores de Endotelina/farmacología , Fiebre/metabolismo , Fiebre/inducido químicamente

RESUMEN

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that is expressed in several brain locations encompassing the hypothalamus and the brainstem, where the receptor controls several body functions, including metabolism. In a well-defined pathway to decrease appetite, hypothalamic proopiomelanocortin (POMC) neurons localized in the arcuate nucleus (Arc) project to MC4R neurons in the paraventricular nuclei (PVN) to release the natural MC4R agonist α-melanocyte-stimulating hormone (α-MSH). Arc neurons also project excitatory glutamatergic fibers to the MC4R neurons in the PVN for a fast synaptic transmission to regulate a satiety pathway potentiated by α-MSH. By using super-resolution microscopy, we found that in hypothalamic neurons in a primary culture, postsynaptic density protein 95 (PSD95) colocalizes with GluN1, a subunit of the ionotropic N-methyl-D-aspartate receptor (NMDAR). Thus, hypothalamic neurons form excitatory postsynaptic specializations. To study the MC4R distribution at these sites, tagged HA-MC4R under the synapsin promoter was expressed in neurons by adeno-associated virus (AAV) gene transduction. HA-MC4R immunofluorescence peaked at the center and in proximity to the PSD95- and NMDAR-expressing sites. These data provide morphological evidence that MC4R localizes together with glutamate receptors at postsynaptic and peri-postsynaptic sites.

Asunto(s)

Hipotálamo , Neuronas , Receptor de Melanocortina Tipo 4 , Animales , Receptor de Melanocortina Tipo 4/metabolismo , Receptor de Melanocortina Tipo 4/genética , Neuronas/metabolismo , Hipotálamo/metabolismo , Hipotálamo/citología , Ratones , Sinapsis/metabolismo , Homólogo 4 de la Proteína Discs Large/metabolismo , Células Cultivadas , Receptores de N-Metil-D-Aspartato/metabolismo

RESUMEN

In parallel to the legalization of cannabis for both medicinal and recreational purposes, cannabinoid use has steadily increased over the last decade in the United States. Cannabinoids, such as tetrahydrocannabinol and anandamide, bind to the central cannabinoid-1 (CB1) receptor to impact several physiological processes relevant for body weight regulation, including appetite and energy expenditure. The hypothalamus integrates peripheral signals related to energy balance, houses several nuclei that orchestrate eating, and expresses the CB1 receptor. Herein we review literature to date concerning cannabinergic action in the hypothalamus with a specific focus on eating behaviors. We highlight hypothalamic areas wherein researchers have focused their attention, including the lateral, arcuate, paraventricular, and ventromedial hypothalamic nuclei, and interactions with the hormone leptin. This review serves as a comprehensive analysis of what is known about cannabinoid signaling in the hypothalamus, highlights gaps in the literature, and suggests future directions.

Asunto(s)

Cannabinoides , Conducta Alimentaria , Hipotálamo , Receptor Cannabinoide CB1 , Transducción de Señal , Humanos , Animales , Hipotálamo/metabolismo , Conducta Alimentaria/fisiología , Receptor Cannabinoide CB1/metabolismo , Leptina/metabolismo , Metabolismo Energético

RESUMEN

Light is fundamental for biological life, with most mammals possessing light-sensing photoreceptors in various organs. Opsin3 is highly expressed in adipose tissue which has extensive communication with other organs, particularly with the brain through the sympathetic nervous system (SNS). Our study reveals a new light-triggered crosstalk between adipose tissue and the hypothalamus. Direct blue-light exposure to subcutaneous white fat improves high-fat diet-induced metabolic abnormalities in an Opsin3-dependent manner. Metabolomic analysis shows that blue light increases circulating levels of histidine, which activates histaminergic neurons in the hypothalamus and stimulates brown adipose tissue (BAT) via SNS. Blocking central actions of histidine and denervating peripheral BAT blunts the effects of blue light. Human white adipocytes respond to direct blue light stimulation in a cell-autonomous manner, highlighting the translational relevance of this pathway. Together, these data demonstrate a light-responsive metabolic circuit involving adipose-hypothalamus communication, offering a potential strategy to alleviate obesity-induced metabolic abnormalities.

Asunto(s)

Tejido Adiposo Pardo , Hipotálamo , Luz , Animales , Hipotálamo/metabolismo , Hipotálamo/efectos de la radiación , Humanos , Tejido Adiposo Pardo/metabolismo , Masculino , Ratones , Obesidad/metabolismo , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Opsinas de Bastones/metabolismo , Sistema Nervioso Simpático/metabolismo , Tejido Adiposo/metabolismo , Neuronas/metabolismo , Neuronas/efectos de la radiación , Tejido Adiposo Blanco/metabolismo , Tejido Adiposo Blanco/efectos de la radiación , Adipocitos Blancos/metabolismo , Adipocitos Blancos/efectos de la radiación

RESUMEN

Prolonged or chronic social isolation has pronounced effects on animals, ranging from altered stress responses, increased anxiety and aggressive behaviour, and even increased mortality. The effects of shorter periods of isolation are much less well researched; however, short periods of isolation are used routinely for testing animal behaviour and physiology. Here, we studied how a 3 h period of isolation from a cagemate affected neural gene expression in three brain regions that contain important components of the social decision-making network, the hypothalamus, the nucleus taeniae of the amygdala, and the bed nucleus of the stria terminalis, using a gregarious bird as a model (zebra finches). We found evidence suggestive of altered neural activity, synaptic transmission, metabolism, and even potentially pain perception, all of which could create cofounding effects on experimental tests that involve isolating animals. We recommend that the effects of short-term social isolation need to be better understood and propose alternatives to isolating animals for testing.

Asunto(s)

Toma de Decisiones , Pinzones , Aislamiento Social , Animales , Aislamiento Social/psicología , Pinzones/fisiología , Masculino , Conducta Animal , Encéfalo/metabolismo , Encéfalo/fisiología , Núcleos Septales/metabolismo , Conducta Social , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/fisiología , Hipotálamo/metabolismo

RESUMEN

According to the synaptic homeostasis hypothesis (SHY), sleep serves to renormalize synaptic connections that have been potentiated during the prior wake phase due to ongoing encoding of information. SHY focuses on glutamatergic synaptic strength and has been supported by numerous studies examining synaptic structure and function in neocortical and hippocampal networks. However, it is unknown whether synaptic down-regulation during sleep occurs in the hypothalamus, i.e., a pivotal center of homeostatic regulation of bodily functions including sleep itself. We show that sleep, in parallel with the synaptic down-regulation in neocortical networks, down-regulates the levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) in the hypothalamus of rats. Most robust decreases after sleep were observed at both sites for AMPARs containing the GluA1 subunit. Comparing the effects of selective rapid eye movement (REM) sleep and total sleep deprivation, we moreover provide experimental evidence that slow-wave sleep (SWS) is the driving force of the down-regulation of AMPARs in hypothalamus and neocortex, with no additional contributions of REM sleep or the circadian rhythm. SWS-dependent synaptic down-regulation was not linked to EEG slow-wave activity. However, spindle density during SWS predicted relatively increased GluA1 subunit levels in hypothalamic synapses, which is consistent with the role of spindles in the consolidation of memory. Our findings identify SWS as the main driver of the renormalization of synaptic strength during sleep and suggest that SWS-dependent synaptic renormalization is also implicated in homeostatic control processes in the hypothalamus.

Asunto(s)

Hipotálamo , Receptores AMPA , Sueño de Onda Lenta , Sinapsis , Animales , Receptores AMPA/metabolismo , Hipotálamo/metabolismo , Masculino , Sinapsis/metabolismo , Sinapsis/fisiología , Ratas , Sueño de Onda Lenta/fisiología , Sueño REM/fisiología , Privación de Sueño/metabolismo , Privación de Sueño/fisiopatología , Sueño/fisiología , Neocórtex/metabolismo , Homeostasis , Ratas Sprague-Dawley , Regulación hacia Abajo , Ratas Wistar

RESUMEN

Brain nuclei are traditionally defined by their anatomy, activity, and expression of specific markers. The hypothalamus contains discrete neuronal populations that coordinate fundamental behavioral functions, including sleep and wakefulness, in all vertebrates. Particularly, the diverse roles of hypocretin/orexin (Hcrt)-releasing neurons suggest functional heterogeneity among Hcrt neurons. Using single-cell RNA sequencing (scRNA-seq) and high-resolution imaging of the adult male and female zebrafish hypothalamic periventricular zone, we identified 21 glutamatergic and 28 GABAergic cell types. Integration of zebrafish and mouse scRNA-seq revealed evolutionary conserved and divergent hypothalamic cell types. The expression of specific genes, including npvf, which encodes a sleep-regulating neuropeptide, was enriched in subsets of glutamatergic Hcrt neurons in both larval and adult zebrafish. The genetic profile, activity, and neurite processing of the neuronal subpopulation that coexpresses both Hcrt and Npvf (Hcrt+Npvf+) differ from other Hcrt neurons. These interspecies findings provide a unified annotation of hypothalamic cell types and suggest that the heterogeneity of Hcrt neurons enables multifunctionality, such as consolidation of both wake and sleep by the Hcrt- and Npvf-releasing neuronal subpopulation.

Asunto(s)

Hipotálamo , Neuronas , Orexinas , Análisis de la Célula Individual , Pez Cebra , Animales , Orexinas/metabolismo , Orexinas/genética , Neuronas/metabolismo , Femenino , Análisis de la Célula Individual/métodos , Ratones , Masculino , Hipotálamo/citología , Hipotálamo/metabolismo , Evolución Biológica

RESUMEN

Segmentation of brain structures on magnetic resonance imaging (MRI) is a highly relevant neuroimaging topic, as it is a prerequisite for different analyses such as volumetry or shape analysis. Automated segmentation facilitates the study of brain structures in larger cohorts when compared with manual segmentation, which is time-consuming. However, the development of most automated methods relies on large and manually annotated datasets, which limits the generalizability of these methods. Recently, new techniques using synthetic images have emerged, reducing the need for manual annotation. Here we provide a dataset composed of label maps built from publicly available ultra-high resolution ex vivo MRI from 10 whole hemispheres, which can be used to develop segmentation methods using synthetic data. The label maps are obtained with a combination of manual labels for the hypothalamic regions and automated segmentations for the rest of the brain, and mirrored to simulate entire brains. We also provide the pre-processed ex vivo scans, as this dataset can support future projects to include other structures after these are manually segmented.

Asunto(s)

Hipotálamo , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Humanos , Hipotálamo/diagnóstico por imagen , Neuroimagen