-
Frontiers in Pharmacology 2022Long-term use of olanzapine can induce various side effects such as lipid metabolic disorders, but the mechanism remains to be elucidated. The gut microbiota-brain axis...
Long-term use of olanzapine can induce various side effects such as lipid metabolic disorders, but the mechanism remains to be elucidated. The gut microbiota-brain axis plays an important role in lipid metabolism, and may be related to the metabolic side effects of olanzapine. Therefore, we explored the mechanism by which olanzapine-induced lipid disturbances through the gut microbiota-brain axis. Sprague Dawley rats were randomly divided into two groups, which underwent subphrenic vagotomy and sham surgery. Then the two groups were further randomly divided into two subgroups, one was administered olanzapine (10 mg/kg/day) by intragastric administration, and the other was administered normal saline by intragastric administration (4 ml/kg/day) for 2 weeks. The final changes in lipid parameters, gut microbes and their metabolites, and orexin-related neuropeptides in the hypothalamus were investigated among the different groups. Olanzapine induced lipid disturbances as indicated by increased weight gain, elevated ratio of white adipose tissue to brown adipose tissue, as well as increased triglyceride and total cholesterol. Olanzapine also increased the Firmicutes/Bacteroides (F/B) ratio in the gut, which was even aggravated by subphrenic vagotomy. In addition, olanzapine reduced the abundance of short-chain fatty acids (SCFAs) metabolism related microbiome and 5-hydroxytryptamine (5-HT) levels in the rat cecum, and increased the gene and protein expression of the appetite-related neuropeptide Y/agouti-related peptide (NPY/AgRP) in the hypothalamus. The abnormal lipid metabolism caused by olanzapine may be closely related to the vagus nerve-mediated gut microbiota-brain axis.
PubMed: 35991866
DOI: 10.3389/fphar.2022.897926 -
Frontiers in Cardiovascular Medicine 2021Butyrate, a short-chain fatty acid (SCFA) produced by the intestinal microbiota, plays a protective role in cardiovascular diseases (CVDs), but the mechanisms involved...
Butyrate, a short-chain fatty acid (SCFA) produced by the intestinal microbiota, plays a protective role in cardiovascular diseases (CVDs), but the mechanisms involved in this process remain unelucidated. We aimed to explore the effect of butyrate on myocardial ischemia/reperfusion (I/R) injury through the gut-brain neural circuit. Rats were randomly divided into four groups: sham group (sham), I/R group (I/R), I/R+ butyrate group (butyrate), and I/R+ butyrate+ vagotomy group (vagotomy). The rats were treated with sodium butyrate for 4 weeks, and the gut-brain neural circuit was investigated by subdiaphragmatic vagotomy. Butyrate treatment significantly reduced the infarct size and decreased the expression of creatine kinase (CK), creatine kinase myocardial isoenzyme (CK-MB), and lactate dehydrogenase (LDH) compared with the values found for the I/R group. In addition, the I/R-induced increases in inflammation, oxidative stress, and apoptosis were attenuated by butyrate. However, the above-mentioned protective effects were diminished by subdiaphragmatic vagotomy. The RNA sequencing results also revealed that the butyrate-induced protective changes at the cardiac transcription level were reversed by vagotomy. An analysis of the heart rate variability (HRV) and the detection of norepinephrine (NE) showed that butyrate significantly inhibited the I/R-induced autonomic imbalance, but this inhibition was not observed in the vagotomy group. Butyrate treatment also suppressed the neural activity of the paraventricular nucleus (PVN) and superior cervical ganglion (SCG), and both of these effects were lost after vagotomy. Butyrate treatment significantly improves myocardial I/R injury via a gut-brain neural circuit, and this cardioprotective effect is likely mediated by suppression of the sympathetic nervous system.
PubMed: 34631821
DOI: 10.3389/fcvm.2021.718674 -
Stem Cell Research & Therapy Aug 2020The distal airways of the lung and bone marrow are innervated by the vagus nerve. Vagal α7nAChR signaling plays a key role in regulating lung infection and...
BACKGROUND
The distal airways of the lung and bone marrow are innervated by the vagus nerve. Vagal α7nAChR signaling plays a key role in regulating lung infection and inflammation; however, whether this pathway regulates α7nAChRSca1 cells during lung injury repair remains unknown. We hypothesized that vagal α7nAChR signaling controls α7nAChRSca1 cells, which contribute to the resolution of lung injury.
METHODS
Pneumonia was induced by intratracheal challenge with E. coli. The bone marrow mononuclear cells (BM-MNCs) were isolated from the bone marrow of pneumonia mice for immunofluorescence. The bone marrow, blood, BAL, and lung cells were isolated for flow cytometric analysis by labeling with anti-Sca1, VE-cadherin, p-Akt1, or Flk1 antibodies. Immunofluorescence was also used to examine the coexpression of α7nAChR, VE-cadherin, and p-Akt1. Sham, vagotomized, α7nAChR knockout, and Akt1 knockout mice were infected with E. coli to study the regulatory role of vagal α7nAChR signaling and Akt1 in Sca1 cells.
RESULTS
During pneumonia, BM-MNCs were enriched with α7nAChRSca1 cells, and this cell population proliferated. Transplantation of pneumonia BM-MNCs could mitigate lung injury and increase engraftment in recipient pneumonia lungs. Activation of α7nAChR by its agonist could boost α7nAChRSca1 cells in the bone marrow, peripheral blood, and bronchoalveolar lavage (BAL) in pneumonia. Immunofluorescence revealed that α7nAChR, VE-cadherin, and p-Akt1 were coexpressed in the bone marrow cells. Vagotomy could reduce α7nAChRVE-cadherin and VE-cadherinp-Akt1 cells in the bone marrow in pneumonia. Knockout of α7nAChR reduced VE-cadherin cells and p-Akt1 cells in the bone marrow. Deletion of Akt1 reduced Sca1 cells in the bone marrow and BAL. More importantly, 91.3 ± 4.9% bone marrow and 77.8 ± 4.9% lung α7nAChRSca1VE-cadherin cells expressed Flk1, which is a key marker of endothelial progenitor cells (EPCs). Vagotomy reduced α7nAChRSca1VE-cadherinp-Akt1 cells in the bone marrow and lung from pneumonia mice. Treatment with cultured EPCs reduced ELW compared to PBS treatment in E. coli pneumonia mice at 48 h. The ELW was further reduced by treatment with EPCs combining with α7nAChR agonist-PHA568487 compared to EPC treatments only.
CONCLUSIONS
Vagal α7nAChR signaling regulates α7nAChRSca1VE-cadherin EPCs via phosphorylation of Akt1 during lung injury repair in pneumonia.
Topics: Animals; Escherichia coli; Lung; Lung Injury; Mice; Mice, Knockout; Vagus Nerve; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 32867826
DOI: 10.1186/s13287-020-01892-4 -
PloS One 2020Swallow-breathing coordination is influenced by changes in lung volume, which is modulated by feedback from both vagal and spinal sensory afferents. The purpose of this...
Swallow-breathing coordination is influenced by changes in lung volume, which is modulated by feedback from both vagal and spinal sensory afferents. The purpose of this study was to manipulate feedback from these afferents, with and without a simultaneous mechanical challenge (chest compression), in order to assess the influence of each sensory pathway on swallow in rats. We hypothesized that manipulation of afferent feedback would shift the occurrence of swallow toward the inspiratory phase of breathing. Afferent feedback was perturbed by lidocaine nebulization, extra-thoracic vagotomy, or lidocaine administration to the pleural space in sodium pentobarbital anesthetized rats (N = 43). These different afferent perturbations were performed both in control conditions (no chest compression), and with chest compression. Manipulating pulmonary stretch receptor-mediated volume feedback in male animals decreased swallow occurrence. Female rats appear to rely more on spinal afferent feedback, as swallow occurrence shifted to late expiration with chest compression and vagotomy or lidocaine injections. Results suggest that sex-specific mechanisms modulate swallow-breathing coordination, and that vagal feedback is inhibitory to swallow-related muscles, while spinal feedback from pleural afferents has excitatory effects. This study supports the theory that a balance of vagal and spinal afferent feedback is necessary to maintain an optimal swallow pattern and swallow-breathing coordination.
Topics: Animals; Deglutition; Female; Male; Rats; Rats, Sprague-Dawley; Respiration; Sex Characteristics; Spinal Cord; Vagus Nerve
PubMed: 32525920
DOI: 10.1371/journal.pone.0234194 -
Biomolecules Jan 2020Dementia and cognitive decline are global public health problems. Moderate consumption of alcoholic beverages reduces the risk of dementia and cognitive decline. For... (Review)
Review
Dementia and cognitive decline are global public health problems. Moderate consumption of alcoholic beverages reduces the risk of dementia and cognitive decline. For instance, resveratrol, a polyphenolic compound found in red wine, has been well studied and reported to prevent dementia and cognitive decline. However, the effects of specific beer constituents on cognitive function have not been investigated in as much detail. In the present review, we discuss the latest reports on the effects and underlying mechanisms of hop-derived bitter acids found in beer. Iso-α-acids (IAAs), the main bitter components of beer, enhance hippocampus-dependent memory and prefrontal cortex-associated cognitive function via dopamine neurotransmission activation. Matured hop bitter acids (MHBAs), oxidized components with β-carbonyl moieties derived from aged hops, also enhance memory functions via norepinephrine neurotransmission-mediated mechanisms. Furthermore, the effects of both IAAs and MHBAs are attenuated by vagotomy, suggesting that these bitter acids enhance cognitive function via vagus nerve stimulation. Moreover, supplementation with IAAs attenuates neuroinflammation and cognitive impairments in various rodent models of neurodegeneration including Alzheimer's disease. Daily supplementation with hop-derived bitter acids (e.g., 35 mg/day of MHBAs) may be a safe and effective strategy to stimulate the vagus nerve and thus enhance cognitive function.
Topics: Animals; Beer; Cognition; Cognitive Dysfunction; Cyclohexenes; Diabetes Mellitus, Type 2; Dopamine; Humans; Humulus; Lipid Metabolism; Norepinephrine; Signal Transduction; Terpenes; Vagus Nerve
PubMed: 31940997
DOI: 10.3390/biom10010131 -
BMC Anesthesiology Sep 2021Postoperative nausea and vomiting (PONV) as a clinically most common postoperative complication requires multimodal antiemetic medications targeting at a wide range of... (Observational Study)
Observational Study
BACKGROUND
Postoperative nausea and vomiting (PONV) as a clinically most common postoperative complication requires multimodal antiemetic medications targeting at a wide range of neurotransmitter pathways. Lacking of neurobiological mechanism makes this 'big little problem' still unresolved. We aim to investigate whether gut-vagus-brain reflex generally considered as one of four typical emetic neuronal pathways might be the primary mediator of PONV.
METHODS
Three thousand two hundred twenty-three patients who underwent vagus nerve trunk resection (esophagectomy and gastrectomy) and non-vagotomy surgery (hepatectomy, pulmonary lobectomy and colorectomy) from December 2016 to January 2019 were enrolled. Thirty cases of gastrectomy with selective resection on the gastric branch of vagus nerve were also recruited. Nausea and intensity of vomiting was recorded within 24 h after the operation.
RESULTS
PONV occurred in 11.9% of 1187 patients who underwent vagus nerve trunk resection and 28.7% of 2036 non-vagotomy patients respectively. Propensity score matching showed that vagotomy surgeries accounted for 19.9% of the whole PONV incidence, much less than that observed in the non-PONV group (35.1%, P < 0.01). Multivariate logistic regression result revealed that vagotomy was one of underlying factor that significantly involved in PONV (OR = 0.302, 95% CI, 0.237-0.386). Nausea was reported in 5.9% ~ 8.6% vagotomy and 12 ~ 17% non-vagotomy patients. Most vomiting were mild, being approximately 3% in vagotomy and 8 ~ 13% in non-vagotomy patients, while sever vomiting was much less experienced. Furthermore, lower PONV occurrence (10%) was also observed in gastrectomy undergoing selective vagotomy.
CONCLUSION
Patients undergoing surgeries with vagotomy developed less PONV, suggesting that vagus nerve dependent gut-brain signaling might mainly contribute to PONV.
Topics: Analgesia; Brain; Brain-Gut Axis; Cohort Studies; Female; Humans; Male; Middle Aged; Neural Pathways; Postoperative Nausea and Vomiting; Reflex; Vagus Nerve
PubMed: 34587905
DOI: 10.1186/s12871-021-01449-9 -
Respiratory Physiology & Neurobiology Feb 2022Recurrent laryngeal afferent fibers are primarily responsible for cough in response to mechanical or chemical stimulation of the upper trachea and larynx in the guinea...
Recurrent laryngeal afferent fibers are primarily responsible for cough in response to mechanical or chemical stimulation of the upper trachea and larynx in the guinea pig. Lower airway slowly adapting receptors have been proposed to have a permissive effect on the cough reflex. We hypothesized that vagotomy below the recurrent laryngeal nerve branch would depress mechanically or chemically induced cough. In anesthetized, bilaterally thoracotomized, artificially ventilated cats, thoracic vagotomy nearly eliminated cough induced by mechanical stimulation of the intrathoracic airway, significantly depressed mechanically stimulated laryngeal cough, and eliminated capsaicin-induced cough. These results support an important role of lower airway sensory feedback in the production of tracheobronchial and laryngeal cough in the cat. Further, at least some of this feedback is due to excitation from pulmonary volume-sensitive sensory receptors.
Topics: Anesthesia; Animals; Cats; Cough; Disease Models, Animal; Female; Laryngeal Nerves; Male; Pulmonary Stretch Receptors; Reflex; Respiratory System; Vagotomy
PubMed: 34678475
DOI: 10.1016/j.resp.2021.103805 -
Neurobiology of Disease Dec 20233,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA...
3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported that the gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated the effects of subdiaphragmatic vagotomy (SDV) in modulating the stress resilience effects of MDMA in mice subjected to chronic restrain stress (CRS). Pretreatment with MDMA (10 mg/kg/day for 14 days) blocked anhedonia-like behavior and reduced expression of synaptic proteins and brain-derived neurotrophic factor in the prefrontal cortex (PFC) of CRS-exposed mice. Interestingly, SDV blocked the beneficial effects of MDMA on these alterations in CRS-exposed mice. Analysis of gut microbiome revealed alterations in four measures of α-diversity between the sham + MDMA + CRS group and the SDV + MDMA + CRS group. Moreover, specific microbes differed between the vehicle + CRS group and the MDMA + CRS group, and further differences in microbial composition were observed among all four groups. Untargeted metabolomics analysis showed that SDV prevented the increase in plasma levels of three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] observed in the sham + MDMA + CRS group. Interestingly, positive correlations were found between the plasma levels of two of these compounds and the abundance of several microbes across all groups. In conclusion, our data suggest that the gut-brain axis via the subdiaphragmatic vagus nerve might contribute to the stress resilience of MDMA.
Topics: Humans; Mice; Animals; N-Methyl-3,4-methylenedioxyamphetamine; Brain-Gut Axis; Resilience, Psychological; Prefrontal Cortex; Vagus Nerve
PubMed: 37956855
DOI: 10.1016/j.nbd.2023.106348 -
Frontiers in Behavioral Neuroscience 2022Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral...
BACKGROUND
Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone - a marker of hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus.
MATERIALS AND METHODS
Using microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery.
RESULTS
Our results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes.
DISCUSSION
We propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission.
PubMed: 35874650
DOI: 10.3389/fnbeh.2022.869526 -
Microbiome Jul 2020In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia...
BACKGROUND
In a pilot study, we found that feces transplantation from elderly individuals to mice significantly caused cognitive impairment. Paenalcaligenes hominis and Escherichia coli are increasingly detected in the feces of elderly adults and aged mice. Therefore, we isolated Paenalcaligenes hominis and Escherichia coli from the feces of elderly individuals and aged mice and examined their effects on the occurrence of age-related degenerative cognitive impairment and colonic inflammation in mice.
RESULTS
The transplantation of feces collected from elderly people and aged mice caused significantly more severe cognitive impairment in transplanted young mice than those from young adults and mice. Oral gavage of Paenalcaligenes hominis caused strong cognitive impairment and colitis in specific pathogen-free (SPF) and germ-free mice. Escherichia coli also induced cognitive impairment and colitis in SPF mice. Oral gavage of Paenalcaligenes hominis, its extracellular vesicles (EVs), and/or lipopolysaccharide caused cognitive impairment and colitis in mice. However, celiac vagotomy significantly inhibited the occurrence of cognitive impairment, but not colitis, in mice exposed to Paenalcaligenes hominis or its EVs, whereas its lipopolysaccharide or Escherichia coli had no such effects. Vagotomy also inhibited the infiltration of EVs into the hippocampus.
CONCLUSIONS
Paenalcaligenes hominis, particularly its EVs, can cause cognitive function-impaired disorders, such as Alzheimer's disease, and its EVs may penetrate the brain through the blood as well as the vagus nerve. Video Abstract.
Topics: Aging; Alcaligenaceae; Animals; Cognitive Dysfunction; Colitis; Escherichia coli; Extracellular Vesicles; Fecal Microbiota Transplantation; Feces; Female; Gastrointestinal Microbiome; Humans; Intestines; Male; Mice; Mice, Inbred C57BL; Middle Aged; Pilot Projects; Risk Factors; Vagotomy; Vagus Nerve; Young Adult
PubMed: 32669127
DOI: 10.1186/s40168-020-00881-2