Hypothalamic Neurotransmitters Research Articles

Long-term consumption of rooibos herbal tea affects hypothalamic neurotransmission and social behavior of adult Sprague–Dawley male rats

Abundant in phenolic compounds, “fermented” rooibos herbal tea (FRHT) improves the cognitive performance and exploration of rats, as well as alters the content of monoamines and amino acids in some brain structures. Here, we aim to extend knowledge about the neurochemical and behavioral outcomes of long-term oral FRHT consumption by examining its impact on hypothalamus functions. FRHTs of different leaf-to-water ratios were given to adult male SD rats for 3 months. Their behavior was evaluated in social interaction test. The concentration of hypothalamic monoamines and amino acids was analyzed by HPLC-ECD whereas BDNF/TrkB by Elisa method. It was shown that sustained FRHT consumption did not affect aggression of the rats but was able to increase social deficits, expressed as diminished total time of contact and shorter active social interaction. Upon biochemical investigation, the changes were primarily linked to serotonergic, glutaminergic, and BDNF/TrkB pathway. Decreased 5-HT and TrkB content in the hypothalamus could be linked with social deficits and suggested positive effect on central energy balance, yet the main body mass of animals in the experiment remained unaffected. On the other hand, the reduced hypothalamic serotonin signaling anticipated the influence on hypothalamic–pituitary–adrenal axis and possible diminution of plasma corticosterone level with subsequent behavioral aftermath and lower obesity risk. Our research contributes toward better understanding of the mechanism of action of rooibos tea and its effects within the central nervous system.Graphical abstract

Green tea catechin epigallocatechin gallate alleviates high‐fat diet‐induced obesity in mice by regulating the gut–brain axis

AbstractPlant polyphenols have gained attention in recent years because of their potential to alleviate obesity and metabolic syndrome, protect neurological function, and maintain intestinal function. Here, we evaluated the effect of green tea catechin epigallocatechin gallate (EGCG) to suppress obesity, alleviate intestinal inflammation, and regulate hypothalamic neurotransmitters in high‐fat diet mice. Obese male C57BL/6J mice were gavaged with 25, 50, or 100 mg/kg·body weight (bw) of EGCG or water per day for 6 weeks. The results demonstrated that EGCG significantly reduced bw, fat accumulation, and liver steatosis. EGCG also modulated hypothalamic neurotransmitters such as dopamine and 5‐HTP. Besides, EGCG attenuated the expression of colonic inflammatory factors and barrier damage, increased the gut microbial abundance such as genus Alloprevotella, reduced short‐chain fatty acids, and downregulated the transcription factors. The results suggest that EGCG may alleviate obesity and related metabolic disorders through gut–brain interaction.

Characterization of Ghrelin O-acyltransferase mRNA in channel catfish

Food intake is regulated by the reaction between hypothalamic neurotransmitters and peripheral signals. Ghrelin, known as a hunger hormone, stimulates food intake. Ghrelin O-acyltransferase (GOAT) catalyzes the acylation of medium-chain fatty acids to ghrelin to modify ghrelin activity. GOAT is found in all vertebrates, including fish, and is critical for modifying the activity of ghrelin. We hypothesized that GOAT is critical for regulating food intake because it modifies the activity of ghrelin in channel catfish. However, very little is known about GOAT in channel catfish, including the tissue distribution of its mRNA. We identified the nucleotide sequence that corresponds to the GOAT mRNA in GenBank. The sequencing alignment analysis showed that the sequence similarity between channel catfish GOAT mRNA and those of other fish species was high (>65%) in the region that corresponded to the open reading frame of the channel catfish GOAT mRNA. Examination of the tissue distribution of GOAT mRNA, including the brain, liver, muscle, kidneys, spleen, heart, and small and large intestines, revealed that GOAT mRNA expression was detectable in the brain, small intestine, and muscles. We are currently verifying the results of tissue distribution analysis using quantitative real-time PCR. We are also examining the relationship between changes in food intake and the expression of GOAT mRNA in the brain and muscle using real-time PCR. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Antifatigue effect of sea buckthorn seed oil on swimming fatigue in mice

The effect of sea buckthorn seed oil (SSO) on exercise-induced fatigue in mice was explored. The animals were randomly divided into a normal control group, exercise-induced fatigue group (EFG), SSO low-dose group, SSO medium-dose group, and SSO high-dose group. The mice in all the groups underwent swimming training for 10 days. Those in the treatment groups received different amounts of SSO (0.85, 1.68, and 3.35g/kgBW [body weight]) before the exercise. All the animals were sacrificed on the last day after an exhaustive swimming test, and serum, liver, and brain specimens were collected. In the exhaustive swimming test, the swimming durations in the SSO-treated animals were longer than those in the EFG. Furthermore, SSO reduced serum lactic acid, blood urea nitrogen, and hepatic malondialdehyde levels and increased liver glycogen level, hepatic superoxide dismutase level, hypothalamic dopamine content, and glutathione peroxidase level. The SSO treatment decreased hypothalamic 5-hydroxytryptamine content, lipid hydroperoxide level, NLRP3 inflammasome, and interleukin-1β protein expression in the prefrontal cortex. Furthermore, it promoted the protein expression of nuclear factor erythroid 2-related factor 2 in the liver. SSO exhibited an excellent antifatigue effect, which may be related to its inhibition of oxidative and inflammatory injury and regulation of hypothalamic neurotransmitters. PRACTICAL APPLICATION: In the present study, the effect of sea buckthorn seed oil on fatigue in mice and its potential mechanism were explored. Taken together, the findings provide insight into the potential role of sea buckthorn seed oil in the development of antifatigue drugs.

Isorhynchophylline Regulates the Circadian Rhythm of the Hypothalamus in Spontaneously Hypertensive Rats to Treat Hypertension.

The neurotransmitter metabolism in spontaneously hypertensive rats (SHR) is disordered, and these disturbances in neurotransmitter levels can further exacerbate the development of hypertension. Neurotransmitters can affect the expression of circadian clock genes. To clarify the time-dependent internal mechanism of the imbalance of the target neurotransmitter metabolic rhythm of spontaneously hypertensive rats, the circadian research was carried out by the method of targeted metabolomics and molecular biology technology. We have explored the mechanism of isorhynchophylline regulating the circadian rhythm through the ERK signaling pathway and thus treating hypertension by detecting the changes of central hypothalamic biological clock rhythm genes after isorhynchophylline intervention, from hypothalamic neurotransmitter rhythmicity. The expression of rhythm genes in normal rats showed a certain rhythm at 6 time points, while the expression of rhythm genes in model rats decreased, and the gene rhythm returned to normal after isorhynchophylline treatment. Cosine analysis of 12 neurotransmitters in hypothalamus showed that there were 6 rhythmic neurotransmitters in the normal group, while in the model group, 4 of the 6 neurotransmitters lost their rhythmicity, and the rhythmicity returned to normal after isorhynchophylline intervention. Compared with the normal group, the expression of ERK protein in the model group increased significantly and decreased after isorhynchophylline treatment. The mechanism of isorhynchophylline treating hypertension is not only the regulation of serum neurotransmitters rhythm, but also acting on rhythm genes in the feedback loop of the central biological clock.

Heat stress-induced intestinal barrier damage and dimethylglycine alleviates via improving the metabolism function of microbiota gut brain axis.

Heat stress, a widely occurred in subtropical climate regions, causes ecosystem destruction, and intestine injury in humans and animals. As an important compound in the metabolic pathway of choline, dimethylglycine (DMG) shows anti-inflammatory effects. This study examines the beneficial effects of dietary DMG against heat stress-induced intestine injury and further explores the underlying molecular mechanisms using a broiler model. Here, we showed that DMG supplements exhibited positive effects to growth performance, as evidenced by the significantly increased body weight and feed conversion rate. These therapeutic effects attributed to repaired gut barrier integrity, increased content of anti-inflammatory cytokines IL-10, decreased content of pro-inflammatory cytokines IL-6, and down-regulated gene expression of the NF-κB signaling pathway. DMG treatment led to the reshaping of the gut microbiota composition, mainly increasing the short-chain fatty acid (SCFAs) strains such as Faecalibacterium, and Marvinbryantia. DMG treatment also increased two main members of SCFAs, including acetate acid and isobutyrate. Particularly, distinct effects were found which mediated the tryptophan metabolism in intestines such as increased tryptophan and 5-HT, which further alleviate the occurrence of intestinal barrier damage caused by heat stress. Additionally, DMG treatment promoted neuroendocrine function and stimulated the hypothalamic neurotransmitter metabolism by activating tryptophan metabolism in the hypothalamus. Overall, DMG supplementation effectively reduced the occurrence of intestinal inflammation induced by heat stress through modulating cecal microbial communities and improving the metabolism function of microbiota gut brain axis. Our findings revealed a novel mechanism by which gut microbiota could improve host health.

Long Noncoding RNA LINC00473 Ameliorates Depression-Like Behaviors in Female Mice by Acting as a Molecular Sponge to Regulate miR-497-5p/BDNF Axis.

Background Depression was a common life-threatening psychiatric disorder and occurs more frequently in women than in men. Long noncoding RNAs (lncRNAs), such as LINC00473, had been reported to be involved in the progression of depression. Methods Chronic unpredictable moderate stress in mice (CUMS) was applied to construct a depression model. Subsequently, RT-qPCR was applied to check the level of LINC00473 and microRNA-497-5p (miR-497-5p) in the hippocampal region of the mice induced by CUMS. CUMS mice were injected with lentiviral vectors of LINC00473 (LV-LINC00473), miR-497-5p inhibitor, short hairpin- (sh-) brain-derived neurotrophic factor (sh-BDNF), or miR-497-5p mimic to evaluate depressive behaviors, including sucrose preference test, forced swim test, elevated plus maze, and tail suspension test. Moreover, the production of hypothalamic neurotransmitters was assessed with the usage of ELISA kits. Dual-luciferase reporter assay, RNA pull-down, and RIP analysis were performed to measure the relationship between miR-497-5p and LINC00473 or BDNF. Further, western blot was employed to determine the protein level of BDNF. Results We discovered that LINC00473 level was downregulated in the female mice with depression, but not in male mice. Besides, the depressive behaviors induced by CUMS in mice, including the decrease of sucrose preference and time in open arm, as well as the increase of immobility time and swimming resting time were all ameliorated by LINC00473 overexpression. Moreover, the concentration of neurotransmitters was decreased in CUMS-induced mouse hypothalamus, which was blocked by LV-LINC00473 lentiviral vector administration. Mechanistically, LINC00473 directly targeted miR-497-5p. Absence of miR-497-5p revealed the antidepression effects on CUMS-induced mice, and miR-497-5p upregulation could counter the antidepressive impacts of LINC00473 upregulation on CUMS-induced mice. Furthermore, LINC00473 could target miR-497-5p to modulate BDNF level. Knockdown of BDNF could abrogate the improving influences of miR-497-5p suppression on CUMS-induced depression. Conclusions LINC00473 ameliorated CUMS-caused depression by encouraging BDNF expression via binding to miR-497-5p, which might provide a potential therapeutic target for depression in females.

Integrated 16S rDNA, metabolomics, and TNF-α/NF-κB signaling pathway analyses to explain the modulatory effect of Poria cocos aqueous extract on anxiety-like behavior

BackgroundPoria cocos is an ancient medicine and modern functional food, which exerts excellent effects on anxiety, although its mechanism is unknown. PurposeTo explore the mechanisms of the aqueous extract of P. cocos (PCD) in ameliorating anxiety-like behavior caused by chronic sleep deprivation (CSD). MethodsPCD chemical composition was analyzed by UPLC-QTOF-MS/MS. A CSD rat model was established over 21 days. We examined the effects and mechanisms after 10 days of CSD using open-field tests (OFTs), enzyme-linked immunosorbent assays, 16S rDNA, non-targeted metabolomics, and Western blot analyses. ResultsSixty-two triterpenoids were identified in PCD. CSD-induced anxiety-like behavior was significantly attenuated by PCD treatment. PCD improved hypothalamic neurotransmitters, decreased proinflammatory cytokines, and depressed the proteins expression of tumor necrosis factor (TNF)-α/nuclear factor (NF)-κB signaling pathway. The full-length 16S rDNA sequence of bacterial cells was also sequenced by high-throughput analysis. CSD caused significant changes in the intestinal flora. PCD improved the species diversity and bacterial abundance in the intestines of rats with anxiety. Metabolomics analysis indicated that 12 PCD-related metabolites in serum and 32 PCD-related metabolites in feces were identified, respectively. Metabolite analysis in serum, PCD treatment affected taurine, hypotaurine, cysteine, methionine, glycine, serine, and threonine metabolism, among others. Metabolite analysis in feces showed significant effects of PCD treatment on the metabolism of vitamin B6, tyrosine, drugs, and glycerophospholipid. Additionally, the correlation analysis of heatmaps showed a tight relationship between inflammatory factors, metabolic parameters, and gut microbial phylotypes. ConclusionsPCD relieved anxiety by regulating intestinal flora, regulating metabolic disorders, and inhibiting inflammatory pathways in chronic sleep-deprived rats.

Photoperiodic Changes in Both Hypothalamus Neurotransmitters and Circulating Gonadal Steroids Metabolomic Profiles in Relation to Seasonal Reproduction in Male Quail.

Both hypothalamic neurotransmitters and serum steroid hormones are impacted by photoperiod and have effects on physiology and seasonal reproductive. However, the relationship between circulating gonadal steroids and hypothalamic neurotransmitters underlying different photoperiod is still unclear. To further understand the crosstalk of neurotransmitters and steroids in seasonal reproduction, metabolic changes of 27 neurotransmitters concentrated in hypothalamus tissues and 42 steroids hormones in serum were assessed during two artificial photoperiodic programs. The results showed that photoperiod induce testicular atrophy and recrudescence. In L-to-S groups, significantly decreased levels of testosterone concentration were found in serum (P < 0.001) and increased 11-Dehydrocorticosterone (P < 0.05); Testosterone were almost undetectable at SD_14d. In addition, the hypothalamus exhibited significantly increased arginine and 4-aminobutyric acid (GABA) concentration and decreased serotonin and epinephrine content (P < 0.01 or P < 0.05). Accordingly, serum testosterone and androstenedione became detectable at LD_3d in the S-to-L group and were markedly increase at LD_7d. Furthermore, Serum androstenedione showed a significant increase with long light expose (P < 0.01). Additionally, the hypothalamus exhibited both significantly increased L.Tryptophan and phenylalanine concentration, as well as decreased L-glutamine and L-glutamine.acid content (P < 0.01 or P < 0.05). Serotonin metabolism showed significant differences between L-to-S group and S-to-L group. Furthermore, in the correlation analysis, serum testosterone had a positive correlation with 5-Hydroxyindole-3-acetic acid (5-HIAA), while Androstenedione was significantly negative with L.Tryptophan in L-to-S (P < 0.05). However, in S-to-L group, serum testosterone showed strong negative correlation with both serotonin and 5-HIAA (P < 0.05), but positive correlation with L.Tryptophan (P < 0.01), while Androstenedione was significantly negative correlation with both serotonin (P < 0.05) and L-Glutamine (P < 0.01). Photoperiod also had significant effects on the mRNA expression. We found significant differences in gene expression patterns of both serotonin signaling and steroid biosynthesis, while MAOB, NR5A1, and 3β-HSD showed an opposite tendency between two groups. Taken together, our results revealed that circulating gonadal steroids and hypothalamic neurotransmitters were significantly impact quail’s seasonal reproduction. Circulating gonadal steroids have different effects on neurotransmitter at different photoperiodism, which may coordinately influence the seasonal reproduction of quails.

The macamide relieves fatigue by acting as inhibitor of inflammatory response in exercising mice: From central to peripheral

Macamides are the major and unique bioactive compounds of Lepidium meyenii (Walp.) or Maca. N-benzyl-(9Z, 12Z)-octadecadienamide (N-benzyl-linoleamide) is one of the most biologically active macamides with various pharmacological activities - anti-fatigue, neuroprotective, antioxidant, anti-tumoral activities, anti-inflammatory, and analgesic. In this study, the anti-fatigue properties of N-benzyl-(9Z, 12Z)-octadecadienamide were further evaluated by a weight-loaded forced swimming test. Results indicated N-benzyl-(9Z, 12Z)-octadecadienamide supplementation increased the forelimb grip strength of mice and exercising time remaining on the Rota-rod test. Furthermore, significant decreases in pro-inflammatory factors and reactive oxygen species (ROS) contents were observed in mice receiving N-benzyl-(9Z, 12Z)-octadecadienamide treatment after a 30 min swimming test, which was equivalent to that of caffeine. Histological analysis also indicated that N-benzyl-(9Z, 12Z)-octadecadienamide attenuated damage to the liver in mice by up-regulating the expression of heme oxygenase-1 (HO-1) and inhibiting the expression of Interleukin (IL)-1β during exercise. Pearson correlation analysis suggested peripheral fatigue indexes, including energy sources, metabolites were significantly correlated with inflammatory factors and ROS levels. Likewise, central fatigue parameters are also associated, including hippocampal inflammatory response and hypothalamic neurotransmitters. Hence, macamides can be considered to have great potential as a natural drug with high efficiency and low side effects for fatigue management.

Duodenal infusion of soy protein hydrolysate activates cAMP signaling and hypothalamic neurotransmitter synthesis in pigs.

Neurotransmitters in the brain are important for cognition and memory. As bioactive substrates, whether increased soy protein levels in pigs can promote hypothalamic neurotransmitter synthesis remains unclear. The effect of increased soy protein hydrolysate (SPH) levels in the small intestine of pigs on neurotransmitter precursor supply, hypothalamic neurotransmitter synthesis and underlying molecular processes was investigated by using sixteen pigs (35.2 ± 0.3 kg) infused either with SPH (70 g day-1) or sterile saline (control) twice daily for 15 days via a duodenal fistula. It demonstrated that SPH infusion increased the expression of the neutral amino acid transporter B0AT1 in the jejunal mucosa, the serum tyrosine/large neutral amino acid ratio, the concentrations of serum tyrosine, hypothalamic tyrosine, dopamine and brain-derived neurotrophic factor (BDNF) (P < 0.05). It also increased the jejunal and serum choline, hypothalamic choline and acetylcholine levels (P < 0.05). Hypothalamic transcriptome revealed that differential genes were significantly enriched in the cholinergic synapse, dopaminergic synapse and cyclic adenosine monophosphate (cAMP) signalling pathways, and that the expression of key enzyme genes in the synthesis of acetylcholine and dopamine and dopamine receptors 1 (DRD1) was upregulated by SPH (P < 0.05). Western blotting showed that SPH infusion activated the hypothalamic cAMP signalling pathways. Overall, SPH infusion promoted the synthesis of hypothalamic dopamine and acetylcholine, and the synthesised dopamine promoted BDNF production most likely through the activation of the cAMP signalling pathways by the DRD1.

Protein-carbohydrate interaction effects on energy balance, FGF21, IGF-1, and hypothalamic gene expression in rats.

Amino acids are involved in energy homeostasis, just as are carbohydrates and lipids. Therefore, mechanisms controlling protein intake should operate independently and in combination with systems controlling overall energy intake to coordinate appropriate metabolic and behavioral responses. The objective of this study was to quantify the respective roles of dietary protein and carbohydrate levels on energy balance, plasma fibroblast growth factor 21 (FGF21) and insulin growth factor 1 (IGF-1) concentrations, and hypothalamic neurotransmitters (POMC, NPY, AgRP, and CART). In a simplified geometric framework, 7-wk-old male Wistar rats were fed 12 diets containing 3%-30% protein for 3 wk, in which carbohydrates accounted for 30%-75% of the carbohydrate and fat part of the diet. As a result of this study, most of the studied parameters (body composition, energy expenditure, plasma FGF21 and IGF-1 concentrations, and Pomc/Agrp ratio) responded mainly to the protein content and to a lesser extent to the carbohydrate content in the diet.NEW & NOTEWORTHY As mechanisms controlling protein intake can operate independently and in combination with those controlling energy intakes, we investigated the metabolic and behavioral effects of the protein-carbohydrate interaction. With a simplified geometric framework, we showed that body composition, energy balance, plasma FGF21 and IGF-1 concentrations, and hypothalamic Pomc/Agrp ratio were primarily responsive to protein content and, to a lesser extent, to carbohydrate content of the diet.

Rivaroxaban Modulates TLR4/Myd88/NF-Kβ Signaling Pathway in a Dose-Dependent Manner With Suppression of Oxidative Stress and Inflammation in an Experimental Model of Depression

Depression is a common mental illness leading to upset or anxiety, with a high incidence rate in the world. Depression can lead to suicidal thoughts and behavior. The present study aimed to evaluate the effect of the direct oral anticoagulant rivaroxaban (RVX), in the model of depression induced by chronic unpredicted mild stress (CUMS) in rats. Fifty-six male Wister rats were randomly divided into seven experimental groups (8 rats/group); Group 1: Control group given vehicle per oral (p.o.), Group 2: RVXL-control group (received rivaroxaban 20 mg/kg/day, p.o..), Group 3: RVXH-control group (received rivaroxaban 30 mg/kg/day, p.o.), Group 4: chronic unpredictable mild stress (CUMS) group, Group 5: FLX-treated CUMS group (received fluoxetine 10 mg/kg/day, p.o..), Group 6: RVXL-treated CUMS group (received rivaroxaban 20 mg/kg/day, p.o.), and Group 7: RVXH-treated CUMS group (received rivaroxaban 30 mg/kg/day, p.o.). The rats received the drugs from the first day of the experiment and continued till 4 weeks—the duration of the study. The following were measured: monoamine neurotransmitters, malondialdehyde (MDA), total nitrite/nitrate (NOx), reduced glutathione (GSH), superoxide dismutase (SOD), Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor‐kappa B (NF‐κB), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A). A forced swimming test (FST) was done. Furthermore, histological changes and glial fibrillary acidic protein (GFAP) immunoexpression were evaluated. CUMS showed a significant decrease in hypothalamic neurotransmitters, hippocampal GSH, SOD, BNDF, and VEGF-A with a significant increase in hippocampal MDA, NOx, NF-kβ, Myd88, TLR4, TNF-α, and GFAP immunoexpression. RVX showed significant improvement in all parameters (p -value < 0.0001). In conclusion, RVX in a dose-dependent manner possesses potent ameliorative effects against depression by reducing the oxidative stress and inflammatory process, through the regulation of the TLR4/Myd88/NF-kβ signaling pathway.

The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions

The hypothalamus-pituitary-thyroid axis is one of several hormone regulatory systems from the hypothalamus to the pituitary and ultimately to the peripheral target organs. The hypothalamus and the pituitary gland are in close anatomical proximity at the base of the brain and extended through the pituitary stalk to the sella turcica. The pituitary stalk allows passage of stimulatory and inhibitory hormones and other signal molecules. The target organs are placed in the periphery and function through stimulation/inhibition by the circulating pituitary hormones. The several hypothalamus-pituitary-target organ axis systems interact in very sophisticated and complicated ways and for many of them the interactive and integrated mechanisms are still not quite clear. The diagnosis of central hypothyroidism is complicated by itself but challenged further by concomitant affection of other hypothalamus-pituitary-hormone axes, the dysfunction of which influences the diagnosis of central hypothyroidism. Treatment of both the central hypothyroidism and the other hypothalamus-pituitary axes also influence the function of the others by complex mechanisms involving both central and peripheral mechanisms. Clinicians managing patients with neuroendocrine disorders should become aware of the strong integrative influence from each hypothalamus-pituitary-hormone axis on the physiology and pathophysiology of central hypothyroidism. As an aid in this direction the present review summarizes and highlights the importance of the hypothalamus-pituitary-thyroid axis, pitfalls in diagnosing central hypothyroidism, diagnosing/testing central hypothyroidism in relation to panhypopituitarism, pointing at interactions of the thyroid function with other pituitary hormones, as well as local hypothalamic neurotransmitters and gut-brain hormones. Furthermore, the treatment effect of each axis on the regulation of the others is described. Finally, these complicating aspects require stringent diagnostic testing, particularly in clinical settings with lower or at least altered à priori likelihood of hypopituitarism than in former obvious clinical patient presentations.

Chapter 4 - Morphology and distribution of hypothalamic peptidergic systems

Neuropeptides participate in the regulation of numerous hypothalamic functions that are aimed for sustaining the homeostasis of the organism. These neuropeptides can act in two different levels. They can influence the release of hormones from the adenohypophysis via the portal circulation; in addition, they can act as neurotransmitters/neuromodulators modulating the functioning of numerous hypothalamic neurotransmitter systems. Indeed, most of these peptidergic systems form a complex network in the infundibular and periventricular nuclei of the human hypothalamus, communicating with each other by synaptic connections that may control fundamental physiologic functions. In the present chapter, we provide an overview of the distribution of neuropeptides in the human hypothalamus using immunohistochemistry and high-resolution, three-dimensional mapping.

Associations between disordered gut microbiota and changes of neurotransmitters and short-chain fatty acids in depressed mice

Mounting evidence suggests that gut microbiota can play an important role in pathophysiology of depression, but its specific molecular mechanisms are still unclear. This study was conducted to explore the associations between changes in neurotransmitters and short-chain fatty acids (SCFAs) and altered gut microbiota in depressed mice. Here, the chronic restraint stress (CRS) model of depression was built. The classical behavioral tests were conducted to assess the depressive-like behaviors of mice. The 16S rRNA gene sequence extracted from fecal samples was used to assess the gut microbial composition. Liquid and gas chromatography mass spectroscopy were used to identify neurotransmitters in hypothalamus and SCFAs in fecal samples, respectively. Finally, 29 differential bacteria taxa between depressed mice and control mice were identified, and the most differentially abundant bacteria taxa were genus Allobaculum and family Ruminococcaceae between the two groups. The acetic acid, propionic acid, pentanoic acid, norepinephrine, 5-HIAA and 5-HT were significantly decreased in depressed mice compared to control mice. Genus Allobaculum was found to be significantly positively correlated with acetic acid and 5-HT. Taken together, these results provided novel microbial and metabolic frameworks for understanding the role of microbiota-gut-brain axis in depression, and suggested new insights to pave the way for novel therapeutic methods.

Electroacupuncture at Zusanli and at Neiguan characterized point specificity in the brain by metabolomic analysis

Different point stimulations can induce brain activity in specific regions, and however whether these stimulations affect unique neurotransmitter transmission remains unknown. Therefore, we aimed to investigate the effect of point specificity to the brain by resolving the metabolite profiles. Eighteen Sprague–Dawley rats were randomly divided into three groups: (1) the sham group: sham acupuncture at Zusanli (ST36) without electric stimulation; (2) the Zusanli (ST36) group: electroacupuncture (EA) at ST36; and (3) the Neiguan (PC6) group: EA at PC6. Then, the metabolites from rat brain samples were measured by LC–ESI–MS. The results of a partial least squares discriminant analysis revealed the differences among the sham, ST36, and PC6 groups regarding the relative content of metabolites in the cerebral cortex, hippocampus, and hypothalamus. EA at PC6 resulted in downregulation of adenosine, adrenaline, γ-aminobutyric acid, glycine, and glutamate majorly in hippocampus, and then in cerebral cortex. Otherwise, EA at ST6 resulted in upregulation of adrenaline and arginine in hippocampus, and all stimulations showed barely change of identified neurotransmitters in hypothalamus. These differential metabolite and neurotransmitter profiles prove that brain areas can be modulated by point specificity and may provide a maneuver to understand more details of meridian.

Morphofunctional alterations of the hypothalamic neurons activity during sleep-wake cycle regulation disturbances after experimental traumatic brain injury

Relevance. The study of sleep disorders mechanisms after traumatic brain injury is complicated and poorly understood. Traumatic damage to the structures that are responsible for the sleep-wake cycle regulation is a common cause of sleep disorders after traumatic brain injury. The number of hypothalamic neurotransmitter systems, which are involved in the sleep-wake cycle regulation, could change its functional activity after trauma that suggests their key role in the development of disturbances of this process.&#x0D; The aim of the study was to assess the morphological alterations of the hypothalamus neurons that is involved in the regulation of sleep and wakefulness after traumatic brain injury in an experiment.&#x0D; Methods. For a combined analysis of posttraumatic disturbances of the sleep-wake cycle and morphofunctional changes in the neurotransmitter systems which are involved in the regulation of the sleep-wake cycle, we used a polysomnography in rats during a month and then an immunohistochemical method for estimating the quantify the orexin A, melanin-concentrating hormone, histamine and tyrosine hydroxylase.&#x0D; Results. The number of histamine-containing cells in the tuberomammillary nuclei of the hypothalamus is obviously decreased after traumatic brain injury in animals. This alteration of the degree of immunoreactivity of histamine-containing cells after traumatic brain injury correlated with sleep duration changes in animals. The number of noradrenergic and orexinergic neurons was compare with control animal group.&#x0D; Conclusion. These results suggest that a change in the functional activity of histamine-containing neurons after traumatic brain injury may be the cause of post-traumatic sleep and wakefulness disorders. Our results may lead to a creating of a new approach for a therapy for posttraumatic sleep-wake disturbances.

Hindbrain lactoprivic regulation of hypothalamic neuron transactivation and gluco-regulatory neurotransmitter expression: Impact of antecedent insulin-induced hypoglycemia

Hindbrain energy state shapes hypothalamic control of glucostasis. Dorsal vagal complex (DVC) L-lactate deficiency is a potent glucose-stimulatory signal that triggers neuronal transcriptional activation in key hypothalamic metabolic loci. The energy gauge AMPK is activated in DVC metabolic-sensory A2 noradrenergic neurons by hypoglycemia-associated lactoprivation, but sensor reactivity is diminished by antecedent hypoglycemia (AH). Current research addressed the premise that AH alters hindbrain lactoprivic regulation of hypothalamic metabolic transmitter function. AH did not modify reductions in A2 dopamine-beta-hydroxylase and monocarboxylate-2 (MCT2) protein expression elicited by caudal fourth ventricular delivery of the MCT inhibitor alpha-cyano-4-hydroxycinnamic acid (4CIN), but attenuated 4CIN activation of A2 AMPK. 4CIN constraint of hypothalamic norepinephrine (NE) activity was averted by AH in a site-specific manner. 4CIN induction of Fos immunolabeling in hypothalamic arcuate (ARH), ventromedial (VMN), dorsomedial (DMN) and paraventricular (PVN) nuclei and lateral hypothalamic area (LHA) was avoided by AH. AH affected reactivity of select hypothalamic metabolic neurotransmitter/enzyme marker proteins, e.g. ARH neuropeptide Y, VMN glutamate decarboxylase, DMN RFamide-related peptide-1 and -3, and LHA orexin-A profiles to 4CIN, but did not alleviate drug inhibition of ARH proopiomelanocortin. AH prevented 4CIN augmentation of circulating glucagon, but did not alter hyperglycemic or hypocorticosteronemic responses to that treatment. Results identify hindbrain lactate deficiency as a stimulus for glucagon secretion, and imply that habituation of this critical counter-regulatory hormone to recurring hypoglycemia may involve one or more hypothalamic neurotransmitters characterized here by acclimation to this critical sensory stimulus.

Effects of Shugan Hewei Decoction and active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats

To investigate the effects of Shugan Hewei Decoction and its active substance fractions on behavior and neurotransmitter levels in hypothalamus of depression model rats,and preliminarily explore its possible mechanism. Male SD rats were randomly divided into blank control group,model group,fluoxetine( positive control) group,Shugan Hewei Decoction high and low dose groups,high and low dose groups of three different substance fractions. After 3 weeks' CUMS and social isolation to induce models,intragastrical administration lasted for 7 d. Behavioral experiments( sucrose consumption test,open-field test,and forced swimming test) were then performed to evaluate the depression status of rats. Several neurotransmitters in hypothalamus of rats were determined by LC-MS/MS method,including dapamine( DA),norepinephrine( NE),serotonin( 5-HT),5-indoleacetic acid( 5-HIAA),γ-aminobutyric acid( GABA),and glutamic acid( Glu). As compared with the blank control group,the sucrose consumption was reduced( P<0. 01); the total distance and the number of crossing the central area were also significantly reduced( P< 0. 01,P< 0. 01),while the resting time increased significantly( P<0. 01); the forced swimming time was significantly prolonged( P<0. 01); DA,5-HT,NE,5-HIAA and GABA levels in hypothalamus were significantly reduced( P < 0. 01),while Glue level was significantly increased( P < 0. 01) in model group. As compared with the model group,all the above indexes had changes in fluoxetine group,Shugan Hewei Decoction whole recipe groups,volatile oils group,polysaccharides group,and terpenoids group( P<0. 01 or P<0. 05). Shugan Hewei Decoction whole recipe and its active substance fractions can improve the behavior of depression model rats and may exert anti-depression effects by regulating the content of neurotransmitters in the hypothalamus.