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Scientific Reports Sep 2023Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor...
Antibiotics are increasingly recognized as causing neuropsychiatric side effects including depression and anxiety. Alterations in central serotonin and 5-HT receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with gastrointestinal disorders. Nevertheless, it is still unclear how antibiotics can cause anxiety and depression. In this study, oral administration of cefaclor, a second-generation cephalosporin antibiotic, induced anxiety- and depression-like behaviors and colitis with gut microbiota alteration in mice. Cefaclor reduced serotonin levels and fluctuated 5-HT receptor mRNA expressions such as Htr1a, Htr1b, and Htr6 in the hippocampus. Vagotomy attenuated the cefaclor-induced anxiety- and depression-like symptoms, while the cefaclor-induced changes in gut bacteria alteration and colitis were not affected. Fluoxetine attenuated cefaclor-induced anxiety- and depression-like behaviors. Furthermore, fluoxetine decreased cefaclor-resistant Enterobacteriaceae and Enterococcaceae. Taken together, our findings suggest that the use of antibiotics, particularly, cefaclor may cause gut dysbiosis-dependent anxiety and depression through the microbiota-gut-blood-brain and microbiota-gut-vagus nerve-brain pathway. Targeting antibiotics-resistant pathogenic bacteria may be a promising therapeutic strategy for the treatment of anxiety and depression.
Topics: Animals; Mice; Cefaclor; Depression; Dysbiosis; Fluoxetine; Serotonin; Anti-Bacterial Agents; Vagus Nerve; Colitis
PubMed: 37726354
DOI: 10.1038/s41598-023-42690-1 -
International Urology and Nephrology Jan 2024Although recent literature provides increasing evidence concerning urinary bladder innervation by vagal afferents, the functional aspects and the conditions at which...
PURPOSE
Although recent literature provides increasing evidence concerning urinary bladder innervation by vagal afferents, the functional aspects and the conditions at which these afferents are recruited are still unclear.
METHODS
In the present study, the neuronal responses of nodose ganglion following cystometry, under different models of rat's urinary bladder irritation, cyclophosphamide (CYP), cyclophosphamide with cervical vagotomy (Vx), chronic HCl, and acute HCl, were investigated using c-fos immunohistochemistry.
RESULTS
The c-fos expression in the nodose ganglion, following cystometry, was increased significantly in the CYP and chronic-HCl groups compared to the intact, Vx, and acute-HCl groups. In addition, the acute-HCl group showed a significant increase compared to intact animals. Following cervical vagotomy, the expression in the Vx group decreased significantly compared to the CYP group, but was significantly higher than that in the intact group.
CONCLUSION
The results of this study demonstrate the innervation of the vagus afferents to the urinary bladder. This innervation is activated under urinary bladder irritation conditions, which may indicate a possible role of the vagus nerve during urinary bladder pathology.
Topics: Rats; Animals; Urinary Bladder; Immunohistochemistry; Vagus Nerve; Cyclophosphamide
PubMed: 37725275
DOI: 10.1007/s11255-023-03791-y -
International Journal of Surgery Case... Oct 2023Pneumatosis cystoides intestinalis (PCI) is defined as the presence of air-filled cysts in the bowel wall. The overall incidence of pneumatosis cystoides intestinalis in...
INTRODUCTION AND IMPORTANCE
Pneumatosis cystoides intestinalis (PCI) is defined as the presence of air-filled cysts in the bowel wall. The overall incidence of pneumatosis cystoides intestinalis in the general population is very rare.
PRESENTATION OF CASE
This is a 44-year-old male patient who presented with epigastric abdominal pain and repeated vomiting of one-month duration. The patient was emaciated; vital signs were within normal limits. The abdomen was grossly distended. Laboratory tests, radiologic imaging, and upper gastrointestinal endoscopy were performed. The diagnosis of gastric outlet obstruction (GOO) secondary to peptic ulcer disease cicatrization along with the coincidental finding of PCI with hepato-diaphragmatic interposition of the small bowel (Chilaiditi sign) was made. Truncal vagotomy, gastrojejunostomy, and Braun jejunojejunostomy was performed. Adhesionolysis and repositioning of the ileum back into its' normal infracolic location was also done.
CLINICAL DISCUSSION
The causes of PCIs are multifactorial; however, the exact etiology is not well known. PCIs have a wide range of non-specific presenting symptoms such as bloody stools, diarrhea or constipation, vomiting, abdominal pain, flatulence, and weight loss. The diagnosis of PCI is made based on endoscopy and radiographic evaluation of the alimentary tract. The appropriate therapy depends on the underlying etiology and the presence of complications.
CONCLUSION
In the absence of complication, PCI can be managed conservatively. However, in the presence of an indication for surgery, PCI related with bowel interposition in the hepato-diaphragmatic space; concomitant repositioning and adhesion release may help to alleviate the symptoms and prevent further complication of PCI.
PubMed: 37716064
DOI: 10.1016/j.ijscr.2023.108828 -
BioRxiv : the Preprint Server For... Sep 2023The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and...
The gut-brain axis, a bidirectional signaling network between the intestine and the central nervous system, is crucial to the regulation of host physiology and inflammation. Recent advances suggest a strong correlation between gut dysbiosis and neurological diseases, however, relatively little is known about how gut bacteria impact the brain. Here, we reveal that gut commensal bacteria can translocate directly to the brain when mice are fed an altered diet that causes dysbiosis and intestinal permeability, and that this also occurs without diet alteration in distinct murine models of neurological disease. The bacteria were not found in other systemic sites or the blood, but were detected in the vagus nerve. Unilateral cervical vagotomy significantly reduced the number of bacteria in the brain, implicating the vagus nerve as a conduit for translocation. The presence of bacteria in the brain correlated with microglial activation, a marker of neuroinflammation, and with neural protein aggregation, a hallmark of several neurodegenerative diseases. In at least one model, the presence of bacteria in the brain was reversible as a switch from high-fat to standard diet resulted in amelioration of intestinal permeability, led to a gradual loss of detectable bacteria in the brain, and reduced the number of neural protein aggregates. Further, in murine models of Alzheimer's disease, Parkinson's disease, and autism spectrum disorder, we observed gut dysbiosis, gut leakiness, bacterial translocation to the brain, and microglial activation. These data reveal a commensal bacterial translocation axis to the brain in models of diverse neurological diseases.
PubMed: 37693595
DOI: 10.1101/2023.08.30.555630 -
International Journal of Cardiology Jan 2024The impact of acute unilateral injury on spontaneous electrical activity in both vagus nerves at the heart level is poorly understood. We investigated the immediate...
BACKGROUND
The impact of acute unilateral injury on spontaneous electrical activity in both vagus nerves at the heart level is poorly understood. We investigated the immediate neuroelectrical response after right or left cardiac vagal nerve transection (VNTx) by recording spiking activity of each heart vagus nerve (VN).
METHODS
Fourteen male Göttingen minipigs underwent sternotomy. Multi-electrode cuffs were implanted below the cut level to record vagal electroneurographic signals during electrocardiographic and hemodynamic monitoring, before and immediately after cardiac VNTx (left: L-cut, n = 6; right: R-cut, n = 8).
RESULTS
Left cardiac VNTx significantly reduced multi-unit electrical activity (MUA) firing rate in the vagal stump (-30.7% vs pre-cut) and intact right VN (-21.8% vs pre-cut) at the heart level, without affecting heart rate, heart rate variability, or hemodynamics. In contrast, right cardiac VNTx did not acutely alter MUA in either VN but slightly increased (p < 0.022) the root mean square of successive RR interval differences (rMSSD), an index of parasympathetic outflow, without affecting hemodynamics.
CONCLUSIONS
Our study reveals an early left-lateralized pattern in vagal spiking activity following unilateral cardiac vagotomy. These findings enhance understanding of the neuroelectrical response to vagal injury and provide insights into preserving vagal outflow after unilateral cardiac vagotomy. Importantly, monitoring spiking activity of the cardiac right VN may predict onset of left vagal pathway injury, which is detrimental to cardiac patients and can occur as a complication of catheter ablation for atrial fibrillation.
Topics: Humans; Male; Swine; Animals; Swine, Miniature; Vagus Nerve; Heart; Vagotomy; Heart Rate
PubMed: 37689397
DOI: 10.1016/j.ijcard.2023.131349 -
BioRxiv : the Preprint Server For... Sep 2023Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the...
Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease (PD). While past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut to brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of the gut mucosa express α-synuclein. In this study, we employed mouse intestinal organoids expressing human α-synuclein to observe the transfer of α-synuclein protein from gut epithelial cells in organoids co-cultured with vagal nodose neurons that are otherwise devoid of α-synuclein expression. In intact mice that express pathological human α-synuclein, but no mouse α-synuclein, α-synuclein fibril templating activity emerges in α-synuclein seeded fibril aggregation assays in tissues from the gut, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human α-synuclein expression to intestinal epithelial cells, α-synuclein fibril-templating activity transfers to the vagus nerve and to the dorsal motor nucleus. Subdiaphragmatic vagotomy prior to the induction of α-synuclein expression in the gut epithelial cells effectively protects the hindbrain from the emergence of α-synuclein fibril templating activity. Overall, these findings highlight a novel potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells.
PubMed: 37645945
DOI: 10.1101/2023.08.14.553305 -
Neuroscience Oct 2023The present study is designed to investigate the role of vagus nerve in the treatments of irritable bowel syndrome (IBS) and the associated central nervous system...
OBJECTIVES
The present study is designed to investigate the role of vagus nerve in the treatments of irritable bowel syndrome (IBS) and the associated central nervous system disorders.
METHODS
An IBS animal model was established by giving acetic acid and chronic-acute stress (AA-CAS) treatment in adult male Wistar rats. Subdiaphragmatic vagotomy (SDV) and vagus nerve stimulation (VNS) were performed to intervene the excitability of vagus nerve. Permeability of blood brain barrier (BBB) was measured and agonist and antagonist of α7 nicotinic acetylcholine receptor (α7nAChR) were used to explore the relevant mechanisms.
RESULTS
AA-CAS treatment resulted in abnormal fecal output, increased visceral sensitivity, depressive-like behaviors, and overexpression of inflammatory mediators, all of which were reversed by VNS treatment. The effects of VNS could also be observed when α7nAChR agonist was applied. Whereas α7nAChR antagonist (methyllycaconitine, MLA) reversed VNS's effects. Interestingly, VNS also reduced the increased permeability of blood brain barrier (BBB) following AA-CAS treatment in IBS rats. SDV treatment only show temporary efficacy on AA-CAS-induced symptoms and had no effect on the permeability of BBB.
CONCLUSION
The intestinal abnormalities and depressive symptoms in IBS rats can be improved by VNS treatment. This positive effect of VNS was achieved through α7nAChR-mediated inflammatory pathway and may also be associated with the decreased of BBB permeability.
PubMed: 37625687
DOI: 10.1016/j.neuroscience.2023.08.026 -
Gut Nov 2023Braak's hypothesis states that Parkinson's disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's...
Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases.
OBJECTIVE
Braak's hypothesis states that Parkinson's disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD.
DESIGN
We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years.
RESULTS
We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p<0.0001) and cohort analyses (relative risks (RRs) vs NCs 2.43, 2.27, 1.17 and 2.38, respectively, all p<0.05). While functional dyspepsia, IBS with diarrhoea, diarrhoea and faecal incontinence were not PD specific, IBS with constipation and intestinal pseudo-obstruction showed PD specificity in the case-control (OR 4.11) and cohort analysis (RR 1.84), respectively. Appendectomy decreased the risk of PD in the cohort analysis (RR 0.48). Neither inflammatory bowel disease nor vagotomy were associated with PD.
CONCLUSION
Dysphagia, gastroparesis, IBS without diarrhoea and constipation might specifically predict Parkinson's disease.
PubMed: 37620120
DOI: 10.1136/gutjnl-2023-329685 -
Bioengineering (Basel, Switzerland) Jul 2023A code is generally defined as a system of signals or symbols for communication. Experimental evidence is synthesized for the presence and utility of such communication... (Review)
Review
A code is generally defined as a system of signals or symbols for communication. Experimental evidence is synthesized for the presence and utility of such communication in heart rate variability (HRV) with particular attention to fetal HRV: HRV contains signatures of information flow between the organs and of response to physiological or pathophysiological stimuli as signatures of states (or syndromes). HRV exhibits features of time structure, phase space structure, specificity with respect to (organ) target and pathophysiological syndromes, and universality with respect to species independence. Together, these features form a spatiotemporal structure, a phase space, that can be conceived of as a manifold of a yet-to-be-fully understood dynamic complexity. The objective of this article is to synthesize physiological evidence supporting the existence of HRV code: hereby, the process-specific subsets of HRV measures indirectly map the phase space traversal reflecting the specific information contained in the code required for the body to regulate the physiological responses to those processes. The following physiological examples of HRV code are reviewed, which are reflected in specific changes to HRV properties across the signal-analytical domains and across physiological states and conditions: the fetal systemic inflammatory response, organ-specific inflammatory responses (brain and gut), chronic hypoxia and intrinsic (heart) HRV (iHRV), allostatic load (physiological stress due to surgery), and vagotomy (bilateral cervical denervation). Future studies are proposed to test these observations in more depth, and the author refers the interested reader to the referenced publications for a detailed study of the HRV measures involved. While being exemplified mostly in the studies of fetal HRV, the presented framework promises more specific fetal, postnatal, and adult HRV biomarkers of health and disease, which can be obtained non-invasively and continuously.
PubMed: 37508849
DOI: 10.3390/bioengineering10070822 -
The Journal of Comparative Neurology Oct 2023The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher-order...
The pyloric sphincter receives parasympathetic vagal innervation from the dorsal motor nucleus of the vagus (DMV). However, little is known about its higher-order neurons and the nuclei that engage the DMV neurons controlling the pylorus. The purpose of the present study was twofold. First, to identify neuroanatomical connections between higher-order neurons and the DMV. This was carried out by using the transneuronal pseudorabies virus PRV-152 injected into rat pylorus torus and examining the brains of these animals for PRV labeling. Second, to identify the specific sites within the DMV that functionally control the motility and tone of the pyloric sphincter. For these studies, experiments were performed to assess the effect of DMV stimulation on pylorus activity in urethane-anesthetized male rats. A strain gauge force transducer was sutured onto the pyloric tonus to monitor tone and motility. L-glutamate (500 pmol/30 nL) was microinjected unilaterally into the rostral and caudal areas of the DMV. Data from the first study indicated that neurons labeled with PRV occurred in the DMV, hindbrain raphe nuclei, midbrain Edinger-Westphal nucleus, ventral tegmental area, lateral habenula, and arcuate nucleus. Data from the second study indicated that microinjected L-glutamate into the rostral DMV results in contraction of the pylorus blocked by intravenously administered atropine and ipsilateral vagotomy. L-glutamate injected into the caudal DMV relaxed the pylorus. This response was abolished by ipsilateral vagotomy but not by intravenously administered atropine or L-NG-nitroarginine methyl ester (L-NAME). These findings identify the anatomical and functional brain neurocircuitry involved in controlling the pyloric sphincter. Our results also show that site-specific stimulation of the DMV can differentially influence the activity of the pyloric sphincter by separate vagal nerve pathways.
Topics: Rats; Male; Animals; Pylorus; Glutamic Acid; Vagus Nerve; Medulla Oblongata; Atropine
PubMed: 37507853
DOI: 10.1002/cne.25530