Hypothalamic Tissue Research Articles

Identification of potential candidate genes and regulatory pathways related to reproductive capacity in hypothalamus and pituitarium of male ducks (Anas platyrhynchos) by differential transcriptome analysis.

The improvement of reproductive capacity of poultry is important for the poultry industry. The existing studies on reproductive capacity mainly focus on the testis tissue, but few reports on regulationary effect of brain neuroendocrime on reproductive capacity have been available. The hypothalamus-pituitarium-gonad (HPG) axis is an important pathway regulating spermatogenesis and sexual behavior. This study analyzed the gene expression in the hypothalamus and pituitary tissues of male ducks in high-semen-quality group (DH), low-semen-quality group (DL), and non-response group (DN) by RNA-sequencing. A total of 1980 differentially expressed genes (DEGs) were identified, and significantly less DEGs were found in pituitary gland than in hypothalamus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DEGs were mainly enriched in nerve-related and synapse-related biological processes, mitochondrial inner membrane formation pathway, and ribosome structure pathway. Notably, the neuroactive ligand-receptor interaction pathway significantly enriched in all three comparisons (DH vs. DL, DH vs. DN, and DL vs. DN) was related to different reproductive performance such as semen quality and sexual response. Furthermore, six genes, including POMC, CPLX2, HAPLN2, EGR4, TOX3, and MSH4, were identified as candidate genes regulating reproductive capacity. Our findings provide new insights into the regulation mechanisms underlying the reproductive performance of male poultry, and offer a valuable reference for duck breeding programs aimed at promoting reproductive capacity.

Identification and characterization of hypothalamic circular RNAs associated with bovine residual feed intake

Residual feed intake (RFI) is crucial economic indicator used for calculating the feed efficiency of growing beef cattle. circRNA plays an important biological role in gene transcriptional regulation, but little is known about its potential functional regulation underlying RFI phenotypic variation. As the core center of regulation of animal feeding, the hypothalamus is closely associated with RFI. Therefore, the present study aimed to identify the key genes and functional pathways contributing to variance in cattle RFI phenotypes using RNA sequencing from hypothalamic tissue samples, in order to gain insight into the potential regulatory role of circRNAs in bovine RFI phenotypic variation. Differentially expressed genes were detected by RNA sequencing for beef cattle in the high and low RFI groups, followed by GO, KEGG enrichment, and circRNA-miRNA co-expression network analysis. A total of 257 circRNAs were differentially expressed between the two groups, with 128 significantly upregulated and 129 significantly downregulated genes in H group compared to L group. Among them, 9 unique circRNAs were present in group L and 4 unique circRNAs were present in group H. GO and KEGG enrichment analysis of the source genes of the differentially expressed circRNAs revealed that they were mainly involved in metabolic processes, such as cellular metabolic processes, cellular macromolecular metabolic processes, and regulatory pathways related to nutrient metabolism, including protein and amino acid metabolism, as well as vitamin metabolism and pancreatic secretion associated with the animal feeding behavior. The circRNAs detected in this study were mostly novel, and have not been investigated directly to be associated with the RFI phenotype. Interestingly, most miRNAs of differentially expressed circRNAs predicted based on the circRNA-miRNA co-expression network analysis by using top 50 differentially expressed circRNAs and 13 unique circRNAs, have been reported to be related to animal RFIs, implying that circRNAs in bovine hypothalamic tissue may regulate phenotypic variation in RFI through miRNAs. The study results illustrate the complex biological functions of the hypothalamus in regulating feed efficiency and showing the potential role of circRNAs in the feeding behavior regulation of livestock, which would contributing to expanding the understanding of circRNA.

Alpha-lipoic acid inhibits oxidative DNA damage of some organs induced by 4-tert-octylphenol exposure in rats

Endocrine disputer chemicals (EDCs) such as 4-tert-octylphenol (OP), are a class of exogenous pollutants that can interfere with normal physiological processes, resulting in a number of health issues. Therefore, the goal of the current study is to determine how well α -lipoic acid (LA) protects against DNA damage brought on by OP. Forty male albino rats were randomly assigned into four groups. Group I (control group) not received any material, group II (αLA-group) received α-lipoic acid (40 mg/kg/ day), group III (OP-group) received 4-tert-octylphenol (50 mg/kg/ day), and group IV(protective group) received 4-tert-octylphenol (50 mg/kg/ day) plus α-lipoic acid (40 mg\ kg/ day) for a period of 30 days. The DNA fragmentations were detected in tissues of hypothalamus, pituitary gland and testis using agarose gel electrophoresis and bands were visualized under UV light and the total DNA concentration in samples were also measured spectrophotometrically. Rats administered OP showed significant (p < 0.05) rising of DNA damage levels in pituitary gland and testis tissues and non-significantly (p >0.05) increase in hypothalamus tissue. On other hand, αLA treatment showed significant (p < 0.05) improvement in DNA damage levels.

Expression of phoenixin-14 and nesfatin-1 in the hypothalamo–pituitary–gonadal axis in the phases of the estrous cycle

Phoenixin-14 (PNX-14) and nucleobindin 2 (NUCB2)/nesfatin-1 are regulatory neuropeptides expressed in the hypothalamus. These neuropeptides can be effective in hormonal regulation of the hypothalamo–pituitary–gonadal (HPG) axis and reproductive functions. In the present study, the distribution of PNX-14 and NUCB2/nesfatin-1 in the hypothalamus, pituitary, ovary, and uterus tissues during the phases of the estrous cycle in female rats was investigated. Eighteen Wistar Albino rats determined among animals showing regular estrous cycle by vaginal smear method were divided into three groups: proestrus (Group I), estrus (Group II) and diestrus (Group III). Serum gonadotropin-releasing hormone (GnRH), plasma PNX-14, and NUCB2/nesfatin-1 concentrations were the highest, moderate, and lowest in estrus, diestrus, and proestrus phases, respectively. PNX-14 immunoreactivity in the supraoptic and arcuate nuclei of the hypothalamus and NUCB2/nesfatin-1 immunoreactivity in the paraventricular nuclei were particularly evident in the estrus phase. These neuropeptide immunoreactivities were decreased in different cells of anterior pituitary during proestrus compared with those during estrus and diestrus. PNX-14 immunoreactivity in the ovary, especially during the estrus phase, was diffuse and intense in the granulosa and luteal cells and oocytes, and it was few and weak in theca cells. In addition, NUCB2/nesfatin-1 immunoreactivity was abundant and strong in granulosa and luteal cells, theca and interstitial cells, and oocytes during estrus. In the estrus phase, PNX-14 immunoreactivity was strong in the glandular epithelial cells and stromal cells of the endometrium, also NUCB2/nesfatin-1 immunoreactivity was strong in the epithelial and glandular epithelial cells. As a result, when the estrous cycle was evaluated, it was concluded that the changes in the distribution of PNX-14 and NUCB2/nesfatin-1 at all phases were related to GnRH and that these neuropeptides showed the highest immunoreactivity especially in the HPG axis and uterus tissues of estrus rats.

Zerumbone, a major sesquiterpene from Syringa pinnatifolia Hemsl., exerts the sedative effect by regulating GABAergic nervous system

Ethnopharmacological relevanceZerumbone (ZER) is a humulane sesquiterpenoid isolated from Syringa pinnatifolia Hemsl. (SP), its content accounts for 64.7% of volatile oil and 0.86% of total ethanol extract (TEE), representing one of characteristic ingredient of SP. As a representative Mongolian medicine with anti-“Khii”, anti-asthma, and clearing-heat effects, SP has been used for the treatment of cardiovascular diseases, upset, insomnia, and other symptoms. Aim of studyPrevious results showed that TEE has sedative effect, but the pharmacological substances and its sedative mechanism remains unclear. This study aims to determine whether ZER, as one of major and characteristic sesquiterpenoids of SP, contributes to the sedative effect of SP and its underlying mechanism. Materials and methodsLocomotor activity and threshold dose of pentobarbital sodium sleep experiments were used to evaluate the sedative effects in mice. ELISA assay was used to examine the level of GABA/Glu ratio in rats hippocampus, cortex and hypothalamus tissue. The binding ability of ZER with glutamic acid decarboxylase 67 (GAD67) and Gephyrin protein were predicted by molecular docking. Western blot and Immunohistochemistry assay were used to determine the expression of GABAergic nerve system related proteins (GAD67, Gephyrin) in rat’s hypothalamus. ZER was co-administrated with flumazenil and bicuculline (GABAA antagonist) to determine whether it acts on GABAA receptor. Furthermore, MQAE assay was used to test the effect of ZER on the chloride ion concentration in cerebellar granule cells. ResultsCurrent data demonstrated that ZER dose-dependently (5–20 mg/kg) reduces the locomotor activity and sleep latency of mice, and extend sleeping time of mice. The results of ELISA showed that ZER increases the level of GABA/Glu in rats brain tissue, in particular in hypothalamus. Molecular docking results revealed that ZER has a strong affinity to GAD67 and Gephyrin protein. The Western blot and Immunohistochemistry data indicated that ZER up-regulates the expression of GAD67 and Gephyrin protein in rat’s hypothalamus. Antagonism test results demonstrated that flumazenil and bicuculline reverse the effect of ZER on threshold dose of pentobarbital sodium sleep experiments. In addition, ZER also could dose-dependently (5–20 μM) increase the chloride ion concentration in cerebellar granule cell, suggesting that ZER induces the opening of chloride channel, exerts central inhibitory effect. ConclusionZER has a significant sedative effect in mice and rat, and the effect is associated with GABAergic nervous system. The present results suggest that ZER, as one of the major bioactive ingredients of SP, contributes to the sedative effect and provide substantial evidence for its traditional use of anti-“Khii” in clinic of Syringa pinnatifolia.

Expression patterns of AMPK and genes associated with lipid metabolism in newly hatched chicks during the metabolic perturbation of fasting and refeeding

Fasting-refeeding perturbation has been extensively used to reveal specific genes and metabolic pathways that control energy metabolism in chickens. In this study, 200 chickens were randomly assigned to 2 groups after hatching: the control group (C, fed ad libitum) and the fasting-refeeding group (T, water ad libitum). The chicks in Group T were fasted for 72 h, and then fed for another 48 h. Liver, hypothalamus, and adipose samples were collected at 0 (F0), 24 (F24), 48 (F48), and 72 h (F72) after fasting and 4 (FR4), 12 (FR12), 24 (FR24), and 48 h (FR48) after refeeding, respectively. Results showed that Group T had a significantly higher number of liver vacuoles (P < 0.05 or P < 0.01) and a significantly lower gray value of Sudan IIIstained sections (P < 0.05 or P < 0.01) than Group C at F48-FR48. In addition, compared with the Group C, fasting and refeeding reduced the expression of stearoyl CoA desaturase (SCD) mRNA (P < 0.05 or P < 0.01) in the liver and adipose tissues, the expression of glucocorticoid receptor (GR) mRNA (P < 0.05 or P < 0.01) in the liver, adipose, and hypothalamus tissues, and the expression of fatty acid synthase (FAS) mRNA (P < 0.05 or P < 0.01) in the liver at F24-FR24. Moreover, relative to those in Group C, fasting and refeeding increased the mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK) α, AMPKβ, and AMPKγ in the hypothalamus (P < 0.05 or P < 0.01) at F24-FR24. In conclusion, fasting and refeeding increased the fat content of the liver, and the expression of lipolytic genes in the hypothalamus (e.g., AMPKα, AMPKβ, and AMPKγ) but decreased the expression of fat synthesis genes in the liver (e.g., SCD, GR, and FAS), adipose (SCD and GR), and hypothalamus (GR).

Long-term exercise training down-regulates m6A RNA demethylase FTO expression in the hippocampus and hypothalamus: an effective intervention for epigenetic modification.

BackgroundExercise boosts the health of some brain parts, such as the hippocampus and hypothalamus. Several studies show that long-term exercise improves spatial learning and memory, enhances hypothalamic leptin sensitivity, and regulates energy balance. However, the effect of exercise on the hippocampus and hypothalamus is not fully understood. The study aimed to find epigenetic modifications or changes in gene expression of the hippocampus and hypothalamus due to exercise.MethodsMale C57BL/6 mice were randomly divided into sedentary and exercise groups. All mice in the exercise group were subjected to treadmill exercise 5 days per week for 1 h each day. After the 12-week exercise intervention, the hippocampus and hypothalamus tissue were used for RNA-sequencing or molecular biology experiments.ResultsIn both groups, numerous differentially expressed genes of the hippocampus (up-regulated: 53, down-regulated: 49) and hypothalamus (up-regulated: 24, down-regulated: 40) were observed. In the exercise group, increased level of N6-methyladenosine (m6A) was observed in the hippocampus and hypothalamus (p < 0.05). Furthermore, the fat mass and obesity-associated gene (FTO) of the hippocampus and hypothalamus were down-regulated in the exercise group (p < 0.001). In addition, the Fto co-expression genes of the mouse brain were studied and analyzed using database to determine the potential roles of exercise-downregulated FTO in the brain.ConclusionThe findings demonstrate that long-term exercise might elevates the levels of m6A-tagged transcripts in the hippocampus and hypothalamus via down-regulation of FTO. Hence, exercise might be an effective intervention for epigenetic modification.

97 Maternal Nutrient Restriction and Melatonin Supplementation Alter Neurotransmitter Profiles in Bovine Fetal and Placental Tissues

Abstract The placenta modulates fetal brain development in mice and humans, with a paucity of information reported in cattle. The objective was to determine the effects of maternal nutrient restriction and melatonin supplementation on neurotransmitter concentrations in the cotyledon, fetal hypothalamus, and fetal blood. At day 160 of gestation, 29 spring-calving and 25 fall-calving Brangus heifers were assigned treatments: adequately fed (ADQ-CON; 100% NRC recommendation), nutrient restricted (RES-CON; 60% NRC recommendation), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL; RES-MEL). Fetuses were removed at day 240 of gestation for collection of placentomes, blood, and hypothalamic tissue. Neurotransmitters (serotonin, 5-HT; dopamine, DA; norepinephrine, NE; epinephrine, EPI) and metabolites (3,4-dihydroxyphenylacetic acid, DOPAC; 5-hydroxyindoleacetic acid, 5-HIAA; homovanillic acid HVA) were analyzed by LCMS or HPLC in blood or tissues, respectively. Data were analyzed by ANOVA using the mixed procedure in SAS with seasons analyzed separately. In spring-calving heifers, melatonin increased (P ≤ 0.05) concentrations of DOPAC, DA, 5-HIAA, and HVA in the cotyledon. Nutrient restriction and melatonin supplementation increased (P ≤ 0.05) blood 5-HT. In both calving seasons, there was a nutrition by treatment interaction in hypothalamic 5-HT (P ≤ 0.01), whereby RES-MEL was increased compared with ADQ-MEL. For fall-calving heifers, no differences were observed in neurotransmitter concentrations in the cotyledon. Hypothalamic NE was increased (P = 0.02) in RES vs. ADQ, while hypothalamic and blood DA were decreased (P ≤ 0.05) in RES vs. ADQ. Hypothalamic 5-HIAA was increased (P = 0.05) in the MEL vs. CON, while blood EPI was decreased (P = 0.04) in MEL vs. CON. In summary, nutrient restriction and melatonin supplementation alter concentrations of neurotransmitters and their metabolites in a seasonally dependent manner. Further investigation into the gene expression of these neurotransmitter pathways is necessary to better define the bovine placental-brain axis.

Acetate restores hypothalamic-adipose kisspeptin status in a rat model of PCOS by suppression of NLRP3 immunoreactivity

Polycystic ovary syndrome (PCOS) is a complex reproductive event that is delineated by endocrine/metabolic disorders. Alteration of kisspeptin status in the hypothalamus and adipose tissue is critical to increased endocrine/metabolic derangements in PCOS individuals, aggravating the clinical manifestation of PCOS and its complications. Short chain fatty acids (SCFAs) are crucial modulators of metabolic homeostasis. However, the role of SCFAs, particularly acetate on hypothalamic-adipose kisspeptin status (HAKS) in PCOS model is unknown. The present study hypothesized acetate as a key player in restoration of deranged HAKS, associated with experimental PCOS model. Three groups (n = 6/group) of female Wistar rats (120-150 g) were used. The groups were treated (po) for 21 days with vehicle, letrozole (1 mg/kg) with/without acetate (200 mg/kg) respectively. Letrozole-treated animals had impaired glucose homeostasis, elevated testosterone, leptin and LH/FSH ratio and decreased GnRH and adiponectin with ovarian tissues revealing degenerated follicles and disrupted morphology. These animals also showed increased concentration of hypothalamic triglyceride (TG)/total cholesterol (TC), free fatty acid (FFA), and decreased concentration of TG/TC/FFA in visceral adipose tissue (VAT) with an increase in hypothalamic and VAT malondialdehyde, NF-κB/TNF-α and decreased glutathione/G6PD and hypothalamic but not VAT kisspeptin. Immunohistochemical analysis revealed the expression of NLRP3 inflammasome in the hypothalamus and VAT and all these changes were attenuated by acetate. Altogether, the present results demonstrate that PCOS is characterized with hypothalamic-adipose inflammation, associated with immunohistochemical expression of NLRP3 with significant alteration of hypothalamic but not adipose kisspeptin. The results suggest that acetate restores kisspeptin status in PCOS animals. This beneficial effect is accompanied by repressed NLRP3 immunoreactivity.

Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel.

Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelus dromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction.

Adult‑onset X‑linked adrenal hypoplasia congenita caused by a novel mutation in DAX1/NR0B1: A case report and literature review

Adrenal hypoplasia congenita (AHC) is a rare X-linked recessive disease caused by mutations in the nuclear receptor subfamily 0, group B, member 1 (NR0B1) gene, which is also referred to as dosage-sensitive sex-reversal, adrenal hypoplasia congenita, in the critical region of the X chromosome, gene 1 (DAX1). This gene is expressed in the hypothalamus, anterior pituitary and steroidogenic tissues, including the gonads and adrenal cortex. Adult-onset forms of X-linked AHC are a significant cause of concern. In the present study, the case of a 21-year-old male who exhibited adrenal insufficiency and hypogonadotropic hypogonadism was described. The patient initially presented with nausea, vomiting, fatigue and dizziness. The laboratory results demonstrated that the patient had hyponatremia, a low basal cortisol concentration and increased adrenocorticotropic hormone levels. Molecular genetic examination revealed a novel frameshift mutation (c.1005delC, p.V336Cfs*36). Following steroid supplementation, the patient's vomiting, fatigue and dizziness rapidly improved. To the best of our knowledge, the present study was the first case report of adult-onset X-linked AHC with this novel frameshift mutation. Furthermore, the present study highlighted differences in the clinical presentation of adult-onset forms of X-linked AHC. This may therefore alert medical professionals to the need to perform genetic analysis for DAX1 mutations in adolescents and adults with primary adrenal insufficiency and hypogonadotropic hypogonadism.

Neuromodulatory and Protective Effects Induced by the Association of Herbal Extracts from Valeriana officinalis, Ziziphus jujuba, and Humulus lupulus with Melatonin: An Innovative Formulation for Counteracting Sleep Disorders

Background: The use of herbal extracts could represent an advantageous approach for treating sleeping disorders, especially in mild-to-moderate conditions, before the onset of a specific therapy with first-line drugs. Specifically, the focus was posed about the use of extracts from Valeriana officinalis, Ziziphus jujuba, and Humulus lupulus. Multiple studies demonstrated the efficacy of these medicinal plants to positively manage insomnia symptoms. Additionally, their efficacy in the treatment of sleeping disorders could also be improved by their pharmacological association. In the present study, extracts from Valeriana officinalis, Ziziphus jujuba, Humulus lupulus, melatonin, and their pharmacological association, Vagonotte® MEL, were studied for potential application in the treatment of insomnia. Methods: The extracts and melatonin were tested on hypothalamic neurons and tissue for evaluating biocompatibility and protective and neuromodulatory effects. The neuromodulatory effects were evaluated as orexin A gene expression and serotonin steady state level, in the hypothalamus. Results: The extracts and melatonin, although with evident differences, were effective as antioxidant and anti-inflammatory agents; additionally, they were also able to reduce the hypothalamic gene expression of orexin A and the steady state level of serotonin, playing master roles in wakefulness. It is noteworthy that the formulation displayed all the effects of the single ingredients, without any sign of toxicity and pharmacological interference in the hypothalamus. Conclusions: Concluding, the present study explored the biological effects of melatonin and herbal extracts with phytotherapy interest in V. officinalis, Z. jujuba, and H. lupulus. The study demonstrated their intrinsic scavenging/reducing activity, together with protective and neuromodulatory effects in the hypothalamus, with a significant reduction of both orexin A gene expression and serotonin steady state level. Additionally, the study also considered their pharmacological association, which displayed an overall pharmacological spectrum mirroring, including all the effects of the single ingredients, without showing any sign of toxicity in the brain and interference between the extracts and melatonin.

Стимулювання системи протеїназа-інгібітор протеїназ у результаті імерсійної гіпотермії

The effect of immersion hypothermia (IН) on proteolysis activity in adult male rats, which was performed at 0 °C for 5 min in the “forced swimming” test, studied; the body temperature decreased to 27.5 ± 0.5°C. In blood serum and non-nuclear fractions of homogenates of cerebral cortex, hypothalamus, cerebellum, brainstem, lungs, heart, liver and kidneys tissues were determined the total proteinase activity (TPA), non-trypsin-like proteinases (NTPs), such as chymase, prostate-specific antigen, partially tonin, kallikrein rK9, as well as trypsin-inhibitory activity of α-1-proteinase inhibitor (α-1-PI), α-2-macroglobulin (α-2-MG) by highly sensitive (10-9–10-10 g) enzymatic methods. It is noted that IH led to the TPA increase in all studied tissues (4-84 times), which corresponds to the psycho-emotional effects and the phenomenon of hormesis. After 24 h, TPA decreased, remaining above the control level, and in the kidneys increased further (90 times). NTLP activity as a result of IH increased in blood serum and cerebellum, decreased in the hypothalamus, and after 24 h increased further in serum (7 times), cerebellum, and heart. The activity of α-1-PI also increased in the brainstem, lungs, heart and kidneys, and decreased after 24 h in serum below the control level, and in the brainstem remained high, protecting against proteolytic attack. The activity of α-2-MG increased in the hypothalamus, heart, and cerebral cortex, maximum in the brainstem (2-5 times), and after 24 h - more significantly (24 times), but there were no changes in the cerebellum, where its initial level is the biggest. Thus, the development of IG as a result of swimming in cold water for 5 min at 0oC has a stimulating effect on the body and leads to a significant activation of the reactions of limited proteolysis.

Exploring the pathological relationships between adamantinomatous craniopharyngioma and contiguous structures with tumor origin.

Identifying relationships between craniopharyngiomas (CPs) and contiguous structures, and tumor origin are crucial fortreatments. This study attempted to explore the relationships and tumor origin. CPs that underwent endoscopic surgeries were enrolled. The interfacial specimens of CPs attaching the hypothalamus, pituitary stalk (PS), pituitary grand (PG), optic chiasma (OC) and brain tissue (BT) were pathologically examined. Boundaries between CPs and these structures were observed during operations. Expression of β-catenin and stem cell markers were analyzed to explore the tumor origin. Outcomes of patients were assessed. A total of 34 CPs were categorized into two groups based on the locations of finger-like protrusions (FP). Group A comprised 18 CPs with FP only present in the specimens attaching to hypothalamus. The surface of these CPs was fused with hypothalamus under endoscopic videos. However, the specimens attaching to the PS, PG, OC, and BT showed no FP. Clear boundaries was observed between these CPs and these structures. Group B comprised 16 CPs with FP only present in the specimens attaching to PS. The tumor surface was fused with PS. Specimens attaching to the hypothalamus, PG, OC and BT showed no FP. Clear boundary was observed among these CPs with these structures. These results implied CPs only invaded a certain part of hypothalamic-pituitary axis. β-catenin and stem cells markers mainly distributed in the FP tissues of both groups. Patients in group B achieved better outcomes than group A. CPs only invade the hypothalamic-pituitary axis with FP and the FP would be the tumor origin.

Copper deposition in Wilson's disease causes male fertility decline by impairing reproductive hormone release through inducing apoptosis and inhibiting ERK signal in hypothalamic-pituitary of mice.

Wilson’s disease (WD) is an autosomal recessive disorder of copper metabolism characterized by liver and central nervous system dysfunction. Considerable evidence suggests that infertility is also very common in male patients with WD, but the exact molecular mechanisms involved remain unknown. In order to further investigate the pathological changes in the hypothalamic-pituitary-testicular (HPT) axis and its mechanisms, mice were divided into the normal control group (NC), WD model TX mice group (WD), dimercaptosuccinic acid–treated TX mice group (DMSA), and pregnant horse serum gonadotropin–treated TX mice group (PMSG). The copper content and morphology of hypothalamus and pituitary tissues, the ultrastructure and apoptosis of hypothalamus neurons and pituitary gonadotropin cells, the serum levels of reproductive hormones, and the pregnancy rate and litter size of the female mice were studied. The expression of apoptosis-related proteins and the phosphorylation of extracellular regulatory protein kinase (ERK) 1/2 in the hypothalamus and pituitary were detected. The results showed that the copper content was significantly increased in the WD group, and the histopathological morphology and ultrastructure of the hypothalamus and pituitary were damaged. The levels of the gonadotropin-releasing hormone, the follicle-stimulating hormone, the luteinizing hormone, and testosterone were significantly decreased. The apoptosis rate in the hypothalamus and pituitary was significantly increased. The expressions of proapoptotic proteins Bax and Caspase-3 were significantly increased, the expression of the anti-apoptotic protein Bcl-2 was significantly decreased, and the phosphorylation level of ERK1/2 was significantly decreased. Fertility is significantly reduced. After DMSA intervention, the hypothalamus tissue copper content decreased, the hypothalamus and pituitary tissue morphology and ultrastructure were improved, cell apoptosis was alleviated, the expression of Bax and Caspase-3 was significantly decreased, the expression of Bcl-2 was significantly increased, and the reproductive hormone level, phosphorylation level, and fertility were increased. Fertility was preserved after treatment with PMSG in male TX mice. These results suggest that copper deposition in WD causes male fertility decline by impairing reproductive neuroendocrine hormone release through inducing apoptosis and inhibiting the ERK signal in the hypothalamic–pituitary region. This study can also provide reference for the damage of copper pollution to the male reproductive system.

Hypothalamus-Muscle Parallel Induction of Metabolic Pathways Following Physical Exercise.

The modern lifestyle requires less physical activity and skills during our daily routine, leading to multiple pathologies related to physical disabilities and energy accessibility. Thus, exploring the mechanisms underlying the metabolic regulation of exercise is crucial. Here, we characterized the effect of forced and voluntary endurance exercises on three key metabolic signaling pathways, sirtuins, AMPK, and mTOR, across several metabolic tissues in mice: brain, muscles, and liver. Both voluntary and forced exercises induced AMPK with higher intensity in the first. The comparison between those metabolic tissues revealed that the hypothalamus and the hippocampus, two brain parts, showed different metabolic signaling activities. Strikingly, despite the major differences in the physiology of muscles and hypothalamic tissues, the hypothalamus replicates the metabolic response of the muscle in response to physical exercise. Specifically, muscles and hypothalamic tissues showed an increase and a decrease in AMPK and mTOR signaling, respectively. Overall, this study reveals new insight into the relation between the hypothalamus and muscles, which enhances the coordination within the muscle–brain axis and potentially improves the systemic response to physical activity performance and delaying health inactivity disorders.

Ghrelin and ghrelin receptor (GHSR) in Chinese alligator, alligator sinensis: Molecular characterization, tissue distribution and mRNA expression changes during the active and hibernating periods

The Chinese alligator (Alligator sinensis) is a freshwater crocodilian endemic to China. So far, the endocrine regulation of feeding and growth in Chinese alligator is poorly understood. In this study, the molecular structure and tissue expression profiles of ghrelin and its receptor GHSR in the Chinese alligator were characterized for the first time. The full-length cDNA of ghrelin was 1770 bp, including a 37 bp 5 '-UTR (untranslated region), a 435 bp ORF (open reading frame) and a 1298 bp 3 '-UTR. The ORF encodes a ghrelin precursor, which consists of 145 amino acid residues, including a signal peptide with 52 amino acid residues at the N-terminus, a mature peptide with 28 amino acid residues, and a possibly obestain at the C-terminus. The full-length cDNA of GHSR was 3961 bp, including a 5′-UTR of 375-bp, an ORF of 1059-bp and a 3′ -UTR of 2527-bp. The ORF encodes a protein of 352 amino acid residues containing seven transmembrane domains, with multiple N glycosylation modification sites and conserved cysteine residue sites. The active core “GSSF” of Chinese alligator ghrelin was identical to that of mammals and birds, and the ghrelin binding site of GHSR was similar to that of mammals. The amino acid sequences of both ghrelin and GHSR share high identity with American alligator (Alligator mississippiensis) and birds. Ghrelin was highly expressed in cerebrum, mesencephalon, hypothalamus and multiple peripheral tissues, including lung, stomach and intestine, suggesting that it could play functions in paracrine and/or autocrine manners in addition to endocrine manner. GHSR expression level was higher in hypothalamus, epencephalon and medulla oblongata, and moderate in multiple peripheral tissues including lung, kindey, stomach and oviduct, implicating that ghrelin/GHSR system may participate in the regulation of energy balance, food intake, water and mineral balance, gastrointestinal motility, gastric acid secretion and reproduction. During hibernation, the expression of ghrelin and GHSR in the brain was significantly increased, while ghrelin was significantly decreased in heart, liver, lung, stomach, pancreas and ovary, and GHSR was significantly decreased in heart, liver, spleen, lung, kindey, stomach, ovary and oviduct. These temporal changes in ghrelin and GHSR expression could facilitate the physiological adaption to the hibernation of Chinese alligator. Our study could provide basic data for further studies on the regulation of feeding, physiological metabolism and reproduction of Chinese alligator, which could also be useful for the improvement of artificial breeding of this endangered species.

Sexual Dimorphism in Adipose-Hypothalamic Crosstalk and the Contribution of Aryl Hydrocarbon Receptor to Regulate Energy Homeostasis.

There are fundamental sex differences in the regulation of energy homeostasis. Better understanding of the underlying mechanisms of energy balance that account for this asymmetry will assist in developing sex-specific therapies for sexually dimorphic diseases such as obesity. Multiple organs, including the hypothalamus and adipose tissue, play vital roles in the regulation of energy homeostasis, which are regulated differently in males and females. Various neuronal populations, particularly within the hypothalamus, such as arcuate nucleus (ARC), can sense nutrient content of the body by the help of peripheral hormones such leptin, derived from adipocytes, to regulate energy homeostasis. This review summarizes how adipose tissue crosstalk with homeostatic network control systems in the brain, which includes energy regulatory regions and the hypothalamic–pituitary axis, contribute to energy regulation in a sex-specific manner. Moreover, development of obesity is contingent upon diet and environmental factors. Substances from diet and environmental contaminants can exert insidious effects on energy metabolism, acting peripherally through the aryl hydrocarbon receptor (AhR). Developmental AhR activation can impart permanent alterations of neuronal development that can manifest a number of sex-specific physiological changes, which sometimes become evident only in adulthood. AhR is currently being investigated as a potential target for treating obesity. The consensus is that impaired function of the receptor protects from obesity in mice. AhR also modulates sex steroid receptors, and hence, one of the objectives of this review is to explain why investigating sex differences while examining this receptor is crucial. Overall, this review summarizes sex differences in the regulation of energy homeostasis imparted by the adipose–hypothalamic axis and examines how this axis can be affected by xenobiotics that signal through AhR.

Effects of Vestibular Damage on the Sleep and Expression Level of Orexin in the Hypothalamus of Rats and Its Correlation with Autophagy and Akt Tumor Signal Pathway.

The aim of this study was to investigate the effect of vestibular disruption on autophagy-related proteins and the tumour-associated pathway P13K/Akt in rat sleep and its hypothalamus tissue and to examine whether catechins trigger tumour autophagy. Healthy adult male rats were randomly selected and divided into the vestibular damage group, the sham operation group, and the control group, with 8 rats in each group. A vestibular damage model was established through penetrating the tympanic membrane of the external auditory canal by injecting sodium p-aminophenylarsonate. The electroencephalogram (EGG) activity was used to record the sleep-wakefulness cycle of rats, and the expression levels of hypothalamic orexin (orexin) mRNA and autophagy proteins were detected. Primary hippocampal neurons were intervened with orexin at different concentrations and at different times to detect cell viability and the expression of autophagy protein and P13K/Akt signal pathway protein. The results showed that compared with the control group and the sham operation group, NREM duration in the vestibular damage group decreased significantly (P < 0.05), while its W time increased significantly (P < 0.05). The expression level of orexin mRNA in the hypothalamus of the vestibular damage group was significantly higher than that of the other two groups (P < 0.05), the expression of autophagy microtubule-related proteins LC3B and Beclin-1 increased significantly (P < 0.05), and the protein expression level of p62 decreased significantly (P < 0.05). After orexin intervention, compared with the control group, the expression of Beclin-1 protein that positively correlated with autophagy decreased significantly (P < 0.05) and the expression of mTOR, PDK1, and Akt protein increased significantly (P < 0.05). Compared with the orexin intervention group, the expression of Beclin-1 and LC3B proteins in cells of the orexin receptor inhibitor (Almorexant) group, the autophagy activator (Rapamycin) group, the orexin + Almorexant group, and the orexin + Rapamycin group increased significantly (P < 0.05), and the expression of mTOR, PDK1, and Akt proteins decreased significantly (P < 0.05). Catechins trigger autophagy in part by regulating the p-Akt/p-mTOR and P13K pathways and by stimulating the MAPK pathway. Catechins initiate apoptosis in common tumour types of hepatocellular carcinoma cells by activating autophagy-related pathways. The conclusion is that vestibular damage can affect the sleep-wakefulness cycle of rats; the level of autophagy in hypothalamic tissue is upregulated and may affect cell proliferation and activity through mTOR-P13K/Akt, which has a certain reference value for tumor formation and provides a basis for the research of insomnia or sleep disorders caused by tumors. Autophagy activation is a key process by which catechins promote apoptosis in tumour cells, providing an avenue for more research on the use of catechins-rich diets for cardiovascular protection in the treatment of tumours.

Screening of Differentially Expressed Genes and miRNAs in Hypothalamus and Pituitary Gland of Sheep under Different Photoperiods.

The reproduction of sheep is affected by many factors such as light, nutrition and genetics. The Hypothalamic-pituitary-gonadal (HPG) axis is an important pathway for sheep reproduction, and changes in HPG axis-related gene expression can affect sheep reproduction. In this study, a model of bilateral ovarian removal and estrogen supplementation (OVX + E2) was applied to screen differentially expressed genes and miRNAs under different photoperiods using whole transcriptome sequencing and reveal the regulatory effects of the photoperiod on the upstream tissues of the HPG axis in sheep. Whole transcriptome sequencing was performed in ewe hypothalamus (HYP) and distal pituitary (PD) tissues under short photoperiod 21st day (SP21) and long photoperiod 21st day (LP21). Compared to the short photoperiod, a total of 1813 differential genes (up-regulation 966 and down-regulation 847) and 145 differential miRNAs (up-regulation 73 and down-regulation 72) were identified in the hypothalamus of long photoperiod group. Similarly, 2492 differential genes (up-regulation 1829 and down-regulation 663) and 59 differential miRNAs (up-regulation 49 and down-regulation 10) were identified in the pituitary of long photoperiod group. Subsequently, GO and KEGG enrichment analysis revealed that the differential genes and target genes of differential miRNA were enriched in GnRH, Wnt, ErbB and circadian rhythm pathways associated with reproduction. Combined with sequence complementation and gene expression correlation analysis, several miRNA-mRNA target combinations (e.g., LHB regulated by novel-414) were obtained. Taken together, these results will help to understand the regulatory effect of the photoperiod on the upstream tissues of HPG in sheep.