Mol Brain. 2024 Nov 27;17(1):86. doi: 10.1186/s13041-024-01162-x.

ABSTRACT

Depression, a prevalent neuropsychiatric disorder, involves the dysregulation of neurotransmitters such as dopamine (DA). The restoration of DA balance is a pivotal therapeutic target for this condition. Recent studies have indicated that both antidepressant medications and non-pharmacological treatments, such as transcutaneous auricular vagus nerve stimulation (taVNS), can promote recovery from depressive symptoms. Despite the promise of taVNS as a non-invasive depression therapy, its precise mechanism remains unclear. We hypothesized that taVNS exerts antidepressant effects by modulating the DAergic system. To investigate this, we conducted experiments demonstrating that taVNS in anesthetized mice reduced depressive-like behaviors. However, this effect was abolished when DA neurons in the ventral tegmental area (VTA^DA) were inhibited. Additionally, taVNS in anesthetized mice enhanced VTA^DA activity, providing further evidence to support its antidepressant effects. Overall, our findings suggest that taVNS alleviates depression by augmenting VTA^DA activity, thereby contributing to a more comprehensive understanding of its therapeutic mechanisms.

PMID:39604984 | PMC:PMC11600629 | DOI:10.1186/s13041-024-01162-x

Trends Neurosci. 2024 Nov 27:S0166-2236(24)00223-6. doi: 10.1016/j.tins.2024.11.001. Online ahead of print.

ABSTRACT

A recent study by Kaneko and colleagues provides evidence that developing cranial motor neurons in larval zebrafish refine their input specificity over time, using an activity-dependent mechanism that may depend, in part, on adaptive dendrite extension. These findings illuminate the mechanism by which spatially overlapping motor pools are recruited into distinct motor circuits.

PMID:39609183 | DOI:10.1016/j.tins.2024.11.001

J Clin Med. 2024 Nov 14;13(22):6836. doi: 10.3390/jcm13226836.

ABSTRACT

Background/Objectives: Better understanding of and addressing umbilical entanglement in the third trimester of pregnancy is necessary to estimate its impact on fetal circulation. An analysis of single physiological pregnancies wrapped with one or two coils of the umbilical cord around the neck makes it possible to understand the severity of the problem and distinguish it from perinatal umbilical strangulation. Methods: In an echocardiographic study performed at 32.1 weeks of pregnancy in fetuses with one and two coils of the umbilical cord around the neck, the pulsatility index (PI) and the Tei index for the left (Tei LV) and right ventricle (Tei RV) of the heart were measured to evaluate cardiac function. Results: The study showed significantly higher Tei RV and Tei LV for fetuses with one (93 cases) and two coils of the umbilical cord around the fetal neck (26 cases) with respect to the control group of fetuses (680 cases) with no umbilical cord around the fetal neck, whereas PI UMBA did not differ significantly. Conclusions: Wrapping of the umbilical cord around the fetal neck may affect the study of the fetal heart without any mechanically induced compression of the umbilical vessels in normal pregnancy.

PMID:39598007 | PMC:PMC11594921 | DOI:10.3390/jcm13226836

Mol Cells. 2024 Nov 25:100161. doi: 10.1016/j.mocell.2024.100161. Online ahead of print.

ABSTRACT

The clinical manifestations of Parkinson’s Disease (PD) are driven by aggregation of α-Synuclein (α-Syn) in the brain. However, there is increasing evidence that PD may be initiated in the gut and thence spread to the brain, e.g. via the vagus nerve. Many studies link PD to changes in the gut microbiome, and bacterial amyloid has been shown to stimulate α-syn aggregation. Yet we are not aware of any studies reporting on a direct connection between microbiome components and α-Syn aggregation. Here we report that soluble extract from the gut microbiome of the rats, particularly young rats transgenic for PD, show a remarkably strong ability to inhibit in vitro α-Syn aggregation and keep it natively unfolded and monomeric. The active component(s) are heat-labile molecule(s) of around 30-100 kDa size which are neither nucleic acid nor lipid. Proteomic analysis identified several proteins whose concentrations in different rat samples correlated with the samples’ anti-inhibitory activity, while a subsequent pulldown assay linked the protein chaperone DnaK with the inhibitory activity of young rat’s microbiome, confirmed in subsequent in vitro assays. Remarkably, the microbiome extracts also protected neuroblastoma SH-SY5Y cells and zebrafish embryos against α-Syn toxicity. Our study sheds new light on the gut microbiome as a potential source of protection against PD and opens up for new microbiome-based therapeutic strategies.

PMID:39603509 | DOI:10.1016/j.mocell.2024.100161

Biol Res. 2024 Nov 23;57(1):88. doi: 10.1186/s40659-024-00573-3.

ABSTRACT

BACKGROUND: Outstanding exercise performance has been associated with an exacerbated vagal outflow. Nevertheless, during high-altitude hypobaric-hypoxia (HH), there is a baroreflex-dependent parasympathetic withdrawal and exercise performance deterioration. Notably, vagal control is pivotal in exercise performance, and exogenous oxytocin (OXY) administration has been shown to enhance parasympathetic drive; however, no evidence shows their role in exercise performance during HH. Then, this study aimed to examine the effect of prolonged exogenous oxytocin (OXY) administration on exercise performance during hypobaric hypoxia (HH) in rats.

RESULTS: A vehicle group (n = 6) and an OXY group (n = 6) performed incremental exercise and baroreflex tests during both normobaric normoxia (NN) and HH (PO₂: 100 mmHg, simulated 3,500 m) prior (pre-) and after (post-) 14 days of administration. The results showed that at pre-, there were no significant differences in exercise performance between the two groups, while at post-, the OXY group exhibited similar performance between NN and HH, while the Vehicle group maintained a significant decline in performance at HH compared to NN. At post-, the Vehicle group also demonstrated a reset in the baroreflex and a worse bradycardic response in HH, which was reversed in the OXY group, while the hypoxic ventilatory response was similar in both groups.

CONCLUSION: The findings suggest prolonged OXY administration prevents impaired exercise performance and vagal control during short-term HH.

PMID:39578887 | DOI:10.1186/s40659-024-00573-3

BMJ Open. 2024 Nov 21;14(11):e089650. doi: 10.1136/bmjopen-2024-089650.

ABSTRACT

INTRODUCTION: Thyroid surgery with intraoperative nerve monitoring under total intravenous anaesthesia often requires deeper sedation due to limitations or lack of neuromuscular blocking agents, usually resulting in haemodynamic instability. Remimazolam, a newly developed sedative, is being studied for its effect on the haemodynamic profile of patients undergoing this procedure and compared with propofol.

METHODS AND ANALYSIS: This will be a single-centre, single-blind, randomised, controlled trial in American Society of Anesthesiologists I-III patients between the ages of 18 and 65 who require recurrent laryngeal nerve monitoring for thyroid surgery. Patients will be randomised 1:1 to either remimazolam besylate or propofol, with 142 cases in each group according to a randomised, computer-generated cohort. The primary outcome is the occurrence of hypotension from induction of anaesthesia to full recovery. Secondary outcomes include the administration of vasoactive agents, the number of hypotension or hypertension episodes, the cumulative duration of hypotension or hypertension, the dose of intraoperative rescue sedation and analgesia, the time to extubation and awakening and the incidence of adverse events.

ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Medical Ethics Committee of the Affiliated Cancer Hospital and Institute of Guangzhou Medical University (2023-2024). The study protocol was modified according to the reviewers’ comments, and the revised version was approved by the Ethics Committee (2024 Research Ethics Amendment No. 3). On completion of the study, we will commit to ensuring that the results are made available to the public, regardless of the outcome. This will include either publication in an appropriate journal or oral presentation at academic conferences.

TRIAL REGISTRATION NUMBER: ChiCTR2300076583.

PMID:39578027 | DOI:10.1136/bmjopen-2024-089650

Mol Biol Rep. 2024 Nov 21;52(1):1. doi: 10.1007/s11033-024-10097-4.

ABSTRACT

BACKGROUND: As a multifunctional ecosystem, the human digestive system contains a complex network of microorganisms, collectively known as gut microbiota. This consortium composed of more than 10¹³ microorganisms and Firmicutes and Bacteroidetes are the dominant microbes. Gut microbiota is increasingly recognized for its critical role in physiological processes beyond digestion. Gut microbiota participates in a symbiotic relationship with the host and takes advantage of intestinal nutrients and mutually participates in the digestion of complex carbohydrates and maintaining intestinal functions.

METHOD AND RESULT: We reviewed the neuroactive components produced by gut microbiota. Interestingly, microbiota plays a crucial role in regulating the activity of the intestinal lymphatic system, regulation of the intestinal epithelial barrier, and maintaining the tolerance to food immunostimulating molecules. The gut-brain axis is a two-way communication pathway that links the gut microbiota to the central nervous system (CNS) and importantly is involved in neurodevelopment, cognition, emotion and synaptic transmissions. The connections between gut microbiota and CNS are via endocrine system, immune system and vagus nerve.

CONCLUSION: The gut microbiota produces common neurotransmitters and neuromodulators of the nervous system. These compounds play a role in neuronal functions, immune system regulation, gastrointestinal homeostasis, permeability of the blood brain barrier and other physiological processes. This review investigates the essential aspects of the neurotransmitters and neuromodulators produced by gut microbiota and their implications in health and disease.

PMID:39570444 | DOI:10.1007/s11033-024-10097-4

Heliyon. 2024 Sep 29;10(21):e38675. doi: 10.1016/j.heliyon.2024.e38675. eCollection 2024 Nov 15.

ABSTRACT

BACKGROUND: Acupressure has proven efficacy in symptoms management, making it valuable in clinical practice and patient care. Given the rising number of increasing publications on acupressure, we aimed to analyze the literature from the past 20 years and provided current trends and hotspot for future research directions.

METHODS: Publications on acupressure from January 1, 2004 through May 1, 2024 were retrieved from the Web of Science database. The extracted records underwent thorough analysis based on publication year, research area, journal, countries/regions, organization, authors, and keywords. The bibliometric analysis was conducted using Citespace and Microsoft Excel software.

RESULTS: Of the 1,929 screened records, 770 publications were identified. The annual number of acupressure has gradually increased, with the 45 % of the total publication occurring from 2020 to 2024. Among countries and institutions, China (252 articles) and Hong Kong Polytechnic University (41 articles) have the highest number of publications. Notably, USA and Hong Kong Polytechnic University exhibits the highest centrality score in cooperative network among countries/regions and institutions. Chao Hsing Yeh from the Cizik School of Nursing, University of Texas Health Science Center, was the most prolific author with 22 papers. Evidence-Based Comple Alt, with 53 articles, is the journal with the most publications. According to the keyword, timeline diagram and prominence mapping analysis, we believe that “insomnia”, “labor”, “waist circumference”, “reliability” and “vagus nerve stimulation” related clusters may be new hotspots in the field of acupressure.

CONCLUSION: This study presents the research trajectory of acupressure over the past 20 years, providing a foundation for future research and highlighting the significant contributions of nursing researchers. By analyzing research trends and hotsport, nursing professionals can integrate acupressure more effectively into holistic patient care, improving quality of life, and contributing to traditional Chinese medicine.

PMID:39568827 | PMC:PMC11577180 | DOI:10.1016/j.heliyon.2024.e38675

Seizure. 2024 Nov 8;123:148-151. doi: 10.1016/j.seizure.2024.11.005. Online ahead of print.

ABSTRACT

INTRODUCTION: Individuals with tuberous sclerosis complex (TSC) often present with refractory epilepsy and may be undergoing treatment with vagus nerve stimulation (VNS) to control seizures. Surveillance magnetic resonance imaging (MRI) is necessary to monitor for the renal angiomyolipomas associated with TSC; however, MRI of the abdomen is not approved for patients withVNS therapy. We have many TSC patients with refractory epilelpsy who benefitted from VNS therapy, so we developed an MRI protocol that allows MRI of the abdomen to be performed in these patients to permit safe imaging of their kidneys. Here we report our results using this protocol.

METHODS: We performed a retrospective review for all TSC patients seen from 01/01/1997 to 10/01/2022 at a single center to determine VNS implantation status. Patients with VNS implants and abdomen imaging performed according to the protocol for kidney surveillance were included.

RESULTS: Sixteen patients with 48 total MRIs of the abdomen were found: 34 (71 %) scans were conducted under sedation and 14 (29 %) without sedation. None of the patients reported any adverse effects (pain or discomfort). No instances of VNS dysfunction were noted when re-interrogating the device immediately after completion of the imaging studies or at later neurology follow-up appointments. All MRI scans were of good quality for interpretation.

CONCLUSION: Abdominal MRIs performed in typical VNS exclusion zones were not associated with adverse events or VNS dysfunction. We believe this protocol is safe and permits the best method for monitoring renal disease in TSC patients with VNS.

PMID:39571475 | DOI:10.1016/j.seizure.2024.11.005

Sci Transl Med. 2024 Nov 20;16(774):eadl2184. doi: 10.1126/scitranslmed.adl2184. Epub 2024 Nov 20.

ABSTRACT

Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which are unknown, that shorten the lifespans of 7 million patients worldwide by nearly 10%. Here, we found that decreased autonomic parasympathetic tone resulted in increased IBD susceptibility and mortality in mouse models of disease. Conversely, vagal stimulation restored neuromodulation and ameliorated colitis by inhibiting the posttranslational modification SUMOylation through a mechanism independent of the canonical interleukin-10/α7 nicotinic cholinergic vagal pathway. Colonic biopsies from patients with IBDs and mouse models showed an increase in small ubiquitin-like modifier (SUMO)2 and SUMO3 during active disease. In global genetic knockout mouse models, the deletion of Sumo3 protected against development of colitis and delayed onset of disease, whereas deletion of Sumo1 halted the progression of colitis. Bone marrow transplants from Sumo1-knockout (KO) but not Sumo3-KO mice into wild-type mice conferred protection against development of colitis. Electric stimulation of the cervical vagus nerve before the induction of colitis inhibited SUMOylation and delayed the onset of colitis in Sumo1-KO mice and resulted in milder symptoms in Sumo3-KO mice. Treatment with TAK-981, a first-in-class inhibitor of the SUMO-activating enzyme, ameliorated disease in three murine models of IBD and reduced intestinal permeability and bacterial translocation in a severe model of the disease, suggesting the potential to reduce progression to sepsis. These results reveal a pathway of vagal neuromodulation that reprograms endogenous stress-adaptive responses through inhibition of SUMOylation and suggest SUMOylation as a therapeutic target for IBD.

PMID:39565873 | DOI:10.1126/scitranslmed.adl2184