-
Journal of Hazardous Materials Sep 2023Previous research has indicated that the cholinergic anti-inflammatory pathway (CAP) can regulate the duration and intensity of inflammatory responses. A wide range of...
Previous research has indicated that the cholinergic anti-inflammatory pathway (CAP) can regulate the duration and intensity of inflammatory responses. A wide range of research has demonstrated that PM exposure may induce various negative health effects via pulmonary and systemic inflammations. To study the potential role of the CAP in mediating PM-induced effects, mice were treated with vagus nerve electrical stimulation (VNS) to activate the CAP before diesel exhaust PM (DEP) instillation. Analysis of pulmonary and systemic inflammations in mice demonstrated that VNS significantly reduced the inflammatory responses triggered by DEP. Meanwhile, inhibition of the CAP by vagotomy aggravated DEP-induced pulmonary inflammation. The flow cytometry results showed that DEP influenced the CAP by altering the Th cell balance and macrophage polarization in spleen, and in vitro cell co-culture experiments indicated that this DEP-induced change on macrophage polarization may act via the splenic CD4 T cells. To further confirm the effect of alpha7 nicotinic acetylcholine receptor (α7nAChR) in this pathway, mice were then treated with α7nAChR inhibitor (α-BGT) or agonist (PNU282987). Our results demonstrated that specific activation of α7nAChR with PNU282987 effectively alleviated DEP-induced pulmonary inflammation, while specific inhibition of α7nAChR with α-BGT exacerbated the inflammatory markers. The present study suggests that PM have an impact on the CAP, and CAP may play a critical function in mediating PM exposure-induced inflammatory response. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
Topics: Mice; Animals; Vehicle Emissions; alpha7 Nicotinic Acetylcholine Receptor; Neuroimmunomodulation; Inflammation; Pneumonia; Particulate Matter
PubMed: 37392642
DOI: 10.1016/j.jhazmat.2023.131951 -
Journal of Cerebral Blood Flow and... Aug 2023Social isolation (ISO) is associated with an increased risk and poor outcomes of ischemic stroke. However, the roles and mechanisms of ISO in stroke-associated pneumonia...
Reversal of the detrimental effects of social isolation on ischemic cerebral injury and stroke-associated pneumonia by inhibiting small intestinal T-cell migration into the brain and lung.
Social isolation (ISO) is associated with an increased risk and poor outcomes of ischemic stroke. However, the roles and mechanisms of ISO in stroke-associated pneumonia (SAP) remain unclear. Adult male mice were single- or pair-housed with an ovariectomized female mouse and then subjected to transient middle cerebral artery occlusion. Isolated mice were treated with the natriuretic peptide receptor A antagonist A71915 or anti-gamma-delta (γδ) TCR monoclonal antibody, whereas pair-housed mice were treated with recombinant human atrial natriuretic peptide (rhANP). Subdiaphragmatic vagotomy (SDV) was performed 14 days before single- or pair-housed conditions. We found that ISO significantly worsened brain and lung injuries relative to pair housing, which was partially mediated by elevated interleukin (IL)-17A levels and the migration of small intestine-derived inflammatory γδ T-cells into the brain and lung. However, rhANP treatment or SDV could ameliorate ISO-exacerbated post-stroke brain and lung damage by reducing IL-17A levels and inhibiting the migration of inflammatory γδ T-cells into the brain and lung. Our results suggest that rhANP mitigated ISO-induced exacerbation of SAP and ischemic cerebral injury by inhibiting small intestine-derived γδ T-cell migration into the lung and brain, which could be mediated by the subdiaphragmatic vagus nerve.
Topics: Male; Female; Mice; Humans; Animals; T-Lymphocytes; Brain; Stroke; Pneumonia; Lung; Intestine, Small; Social Isolation; Cell Movement; Mice, Inbred C57BL
PubMed: 37017434
DOI: 10.1177/0271678X231167946 -
Journal of Dairy Science Mar 2023Conceptual models developed over the past century describe 2 key constraints to feed intake (FI) of healthy animals: gut capacity and metabolic demand. Evidence that... (Review)
Review
Conceptual models developed over the past century describe 2 key constraints to feed intake (FI) of healthy animals: gut capacity and metabolic demand. Evidence that greater energy demands (e.g., greater milk production) drive a corresponding increase in caloric intake led to the dominant concept that animals "eat to energy requirements." Although this model provides reasonable initial estimates of FI, it lacks a proposed physiological basis for the control system, does not consider nutrient constraints beyond energy, and fails to explain differential energy intake responses to different fuels. To address these gaps, research has focused on mechanisms for sensing nutrient availability and providing feedback to hypothalamic centers that integrate signals to control feeding behavior. The elimination of FI response to certain nutrients by vagotomy suggests that peripheral tissues play a role in nutrient sensing. These findings and the central role of the liver in metabolic flux led to the development of the hepatic oxidation theory (HOT). According to the HOT, liver energy charge is the regulated variable that induces dietary intake changes and consequently affects whole-body energy balance. Evidence in support of HOT includes associations between hepatic energy charge and meal patterns, increased FI in response to phosphate trapping, and reduced FI in response to phosphate loading. In accordance with the HOT, infusion studies in dairy cattle have consistently demonstrated that providing fuels that either oxidize or stimulate oxidation in the liver decreases FI and energy intake to a greater extent than fuels that bypass the liver. Importantly, this holds true for glucose, which is readily oxidized by nerve cells, but is rarely taken up by the bovine liver. Although the brain integrates multiple signals including those related to gastric distention and illness, the HOT provides a physiological framework for understanding the dominant role the liver likely plays in sensing short-term energy status. Understanding this model provides insights into how to use or bypass the regulatory system to manage FI of animals.
Topics: Cattle; Animals; Appetite; Eating; Feeding Behavior; Energy Intake; Energy Metabolism; Nutrients
PubMed: 36543641
DOI: 10.3168/jds.2022-22429 -
Scientific Reports Jun 2020Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits....
Vagus nerve stimulation (VNS) is a bioelectronic therapy for disorders of the brain and peripheral organs, and a tool to study the physiology of autonomic circuits. Selective activation of afferent or efferent vagal fibers can maximize efficacy and minimize off-target effects of VNS. Anodal block (ABL) has been used to achieve directional fiber activation in nerve stimulation. However, evidence for directional VNS with ABL has been scarce and inconsistent, and it is unknown whether ABL permits directional fiber activation with respect to functional effects of VNS. Through a series of vagotomies, we established physiological markers for afferent and efferent fiber activation by VNS: stimulus-elicited change in breathing rate (ΔBR) and heart rate (ΔHR), respectively. Bipolar VNS trains of both polarities elicited mixed ΔHR and ΔBR responses. Cathode cephalad polarity caused an afferent pattern of responses (relatively stronger ΔBR) whereas cathode caudad caused an efferent pattern (stronger ΔHR). Additionally, left VNS elicited a greater afferent and right VNS a greater efferent response. By analyzing stimulus-evoked compound nerve potentials, we confirmed that such polarity differences in functional responses to VNS can be explained by ABL of A- and B-fiber activation. We conclude that ABL is a mechanism that can be leveraged for directional VNS.
Topics: Action Potentials; Animals; Electrocardiography; Electrodes, Implanted; Heart Rate; Male; Rats; Rats, Sprague-Dawley; Respiratory Rate; Vagus Nerve; Vagus Nerve Stimulation
PubMed: 32513973
DOI: 10.1038/s41598-020-66332-y -
Biomedicines Apr 2023GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body...
GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.
PubMed: 37238993
DOI: 10.3390/biomedicines11051322 -
Nutrients Feb 2022Acetylcholine (ACh) acts as a neurotransmitter and neuromodulator. A small dose of eggplant powder rich in ACh (equivalent to 22 g fresh eggplant/d) has been shown to...
Acetylcholine (ACh) acts as a neurotransmitter and neuromodulator. A small dose of eggplant powder rich in ACh (equivalent to 22 g fresh eggplant/d) has been shown to reduce blood pressure (BP) in individuals with higher BP. Here, we investigated the mechanisms underlying the antihypertensive effects of low-dose orally administered ACh in spontaneously hypertensive rats (SHRs). The effects of ACh on BP and sympathetic nervous activity (SNA), including lumbar SNA (LSNA) and renal SNA (RSNA), were evaluated by subjecting conscious SHRs to a telemetry method. Single oral administration of ACh decreased LSNA and lowered BP. Repeated oral administration of ACh for 30 d decreased RSNA and suppressed the elevated BP. Noradrenaline levels in the urine also decreased. However, vagotomy and co-administration of M3 muscarinic ACh receptor antagonist reversed the BP-lowering effect; the dynamics of non-absorbable orally administered ACh was revealed using stable isotope-labeled ACh. In conclusion, ACh acts on the gastrointestinal M3 muscarinic ACh receptor to increase afferent vagal nerve activity, which decreases SNA by autonomic reflex, suppressing noradrenaline release and lowering BP. This study suggests the use of exogenous ACh as an antihypertensive food supplement for controlling the autonomic nervous system, without absorption into the blood.
Topics: Acetylcholine; Animals; Antihypertensive Agents; Blood Pressure; Hypertension; Rats; Rats, Inbred SHR; Sympathetic Nervous System
PubMed: 35215556
DOI: 10.3390/nu14040905 -
Reproduction (Cambridge, England) Feb 2023In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of...
IN BRIEF
In the proestrus day, the neural and endocrine signals modulate ovarian function. This study shows vagus nerve plays a role in the multisynaptic pathways of communication between the suprachiasmatic nucleus and the ovaries where such neural information determines ovulation.
ABSTRACT
The suprachiasmatic nucleus (SCN) regulates the activity of several peripheral organs through a parasympathetic-sympathetic pathway. Previously, we demonstrated that atropine (ATR) microinjection in the right SCN of rats during proestrus blocks ovulation. In the present study, we analysed whether the vagus nerve is one of the neural pathways by which the SCN regulates ovulation. For this, CIIZ-V strain cyclic rats on the day of proestrus were microinjected with a saline solution (vehicle) or ATR in the right or left SCN, which was followed by ventral laparotomy or ipsilateral vagotomy to the microinjection side. Some animal groups were sacrificed (i) on the same day of the surgery to measure oestradiol, progesterone and luteinizing hormone (LH) levels or (ii) at 24 h after surgery to evaluate ovulation. The left vagotomy in rats microinjected with ATR in the left SCN did not modify ovulation. In rats with ATR microinjection in the right SCN, the right vagotomy increased the levels of steroids and LH on the proestrus and ovulatory response. The present results suggest that the right vagus nerve plays a role in the multisynaptic pathways of communication between the SCN and the ovaries and indicate that such neural information participates in the regulation of the oestradiol and progesterone surge, which triggers the preovulatory peak of LH and determines ovulation.
Topics: Female; Rats; Animals; Progesterone; Luteinizing Hormone; Suprachiasmatic Nucleus; Ovulation; Estradiol; Atropine; Vagus Nerve
PubMed: 36342662
DOI: 10.1530/REP-22-0119 -
Virulence Dec 2021Abnormalities in CD4 T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that...
Abnormalities in CD4 T cell (Th cell) differentiation play an important role in the pathogenesis of viral myocarditis (VMC). Our previous studies demonstrated that activation of the cholinergic anti-inflammatory pathway (CAP) alleviated the inflammatory response. In addition, we observed that right cervical vagotomy aggravates VMC by inhibiting CAP. However, the vagus nerve's effect on differentiation of CD4 T cells has not been studied in VMC mice to date. In this study, we investigated the effects of cervical vagotomy and the α7nAChR agonist pnu282987 on CD4 T cell differentiation in a murine myocarditis model (BALB/c) infected with coxsackievirus B3 (CVB3). Splenic CD4 T cells from CVB3-induced mice obtained and cultured to investigate the potential mechanism of CD4 T cell differentiation. Each Th cell subset was analyzed by flow cytometry. Our results showed that right cervical vagotomy increased proportions of Th1 and Th17 cells and decreased proportions of Th2 and Treg cells in the spleen. Vagotomy-induced upregulation of T-bet, Ror-γ, IFN-γ, and IL-17 expression while downregulating the expression of Gata3, Foxp3, and IL-4 in the heart. In addition, we observed upregulated levels of proinflammatory cytokines, aggravated myocardial lesions and cellular infiltration, and worsened cardiac function in VMC mice. Pnu282987 administration reversed these outcomes. Furthermore, vagotomy inhibited JAK2-STAT3 activation and enhanced NF-κB activation in splenic CD4 T cells. The CD4 T cell differentiation was related to JAK2-STAT3 and NF-κB signal pathways. In conclusion, vagus nerve modulates the inflammatory response by regulating CD4 T cell differentiation in response to VMC.
Topics: Acute Disease; Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Coxsackievirus Infections; Cytokines; Enterovirus B, Human; Male; Mice; Mice, Inbred BALB C; Myocarditis; Vagus Nerve
PubMed: 33380272
DOI: 10.1080/21505594.2020.1869384 -
Neurogastroenterology and Motility Nov 2019We have shown previously that an attenuated rodent model of mild necrotizing enterocolitis (NEC) increases intestinal histopathological severity grade, prevents typical...
BACKGROUND
We have shown previously that an attenuated rodent model of mild necrotizing enterocolitis (NEC) increases intestinal histopathological severity grade, prevents typical developmental increases in the high-frequency spectrum of heart rate variability (HF-HRV), alters the nitrergic myenteric phenotype, and increases IL-6 and IL-1β when combined with anterior subdiaphragmatic vagotomy. The aims of the present study were to test the hypotheses that in mild NEC-induced pups, administration of the orexigenic hormone ghrelin (a) reduces the histopathological score, (b) increases the HF-HRV power, (c) improves the altered myenteric phenotype, and (d) subdiaphragmatic vagotomy prevents the effects of ghrelin.
METHODS
Newborn Sprague Dawley rats were subjected to seven days of brief periods of cold stress and hypoxia to induce mild NEC with or without anterior subdiaphragmatic vagotomy. HRV was measured at postnatal days one, five, and ten; intraperitoneal ghrelin (0.05 mg kg ) was administered postnatal days five through ten b.i.d. Pups were sacrificed at day 12, and whole brains, gastrointestinal tissues, and blood were collected for immunohistochemical, corticosterone, and cytokine analysis.
KEY RESULTS
Ghrelin treatment reduced the intestinal histopathological score, increased the HF-HRV power, improved the altered intestinal myenteric phenotype, and subdiaphragmatic vagotomy prevented the effects of ghrelin. There were no differences in serum cytokines or corticosterone between groups.
CONCLUSIONS AND INFERENCES
Our data suggest that ghrelin administration is able to recover the mild NEC-induced changes to the histology, HF-HRV, and myenteric phenotype in a vagally dependent manner.
Topics: Animals; Animals, Newborn; Enterocolitis, Necrotizing; Ghrelin; Heart Rate; Intestines; Myenteric Plexus; Phenotype; Rats; Rats, Sprague-Dawley
PubMed: 31386261
DOI: 10.1111/nmo.13682 -
Neuroscience Letters Nov 2019Parkinson's disease (PD) is a multifactorial neurodegenerative disorder, affecting 3.7% of the population over 65 years of age. PD involves degeneration of dopaminergic... (Review)
Review
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder, affecting 3.7% of the population over 65 years of age. PD involves degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNPC) with deficiency of dopamine. Genetic factors like SNCA, PARK-2, PARK-7, PINK-1 and LRRK-2 as well as environmental toxins enhance alpha-synuclein, amyloid β (beta) and τ (tau) proteins aggregation. Moreover, oxidative stress, mitochondrial dysfunctioning, neuroinflammation, prion like phenomena, excitotoxicity, mutations etc are known to cause pathological insult in PD. Recently, facts indicates strong correlation between gut-brain axis and PD. The communication between the gastrointestinal system (GIT) and central nervous system is bidirectional and it is hypothesized that PD arises in the gut and spreads to brain via vagus nerve that helps to propagate the alpha-synuclein that target brain. The Lewy bodies are found in olfactory bulb, dorsal motor vagal nerve and the ENS of the gut indicate peripheral and central correlation. The alteration of gut microbial flora leads to GIT disturbance which cause neuroinflammation by prion alpha-synuclein expression and produces PD like symptoms. Persistent gut inflammation with spontaneous neuroinflammation is yet need to confirm but increased intestinal permeability and disrupt function of GIT is known to produce non-motor symptoms of PD. The present review is aimed to explore mechanistic approach for gut associated PD symptoms as well as use of probiotics and prebiotics as therapeutic approach to retain gut microbial flora and prevent PD like symptoms.
Topics: Disease Management; Gastrointestinal Microbiome; Humans; Inflammation; Intestinal Mucosa; Parkinson Disease
PubMed: 31560998
DOI: 10.1016/j.neulet.2019.134516