Neural mechanisms of host-microbiota interaction in hypertension: a potential for bio-electronic medicine

高血压宿主-微生物群相互作用的神经机制：生物电子医学的潜力

• 批准号: 10625276
• 负责人: Jasenka Zubcevic
• 金额: $ 45.13万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625276
• 关键词: Address; Affect; Afferent Neurons; American; Anatomy; Animals; Autonomic nervous system; Blood Pressure; Brain; Calcium; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Chronic; Colon; Data; Dementia; Diabetes Mellitus; Disease; Effectiveness; Electric Stimulation; Electrophysiology (science); Event; Feedback; Fiber; Functional disorder; Future; HTR3A gene; Health; Human; Hypertension; Impairment; Investigation; Kidney Diseases; Length; Life Style Modification; Link; Maps; Mediating; Medicine; Modeling; Molecular; Monitor; Nerve; Neurons; Nodose Ganglion; Norepinephrine; Nucleus solitarius; Obstructive Sleep Apnea; Outcome; Patients; Pattern; Pharmacotherapy; Plasma; Prevention; Production; Public Health; Rat Transgene; Rattus; Receptor Signaling; Reflex action; Refractory; Regulation; Research; Resistance; Resistant Hypertension; Risk Factors; Rodent; Role; Serotonin; Signal Transduction; Site; Stroke; Telemetry; Therapeutic; Time; Tracer; Transgenic Organisms; Transplantation; Vasomotor; Viral; aggressive therapy; bioelectronics; blood pressure elevation; blood pressure reduction; comorbidity; dysbiosis; experimental study; fecal transplantation; gut dysbiosis; gut microbiota; gut-brain axis; host microbiota; human microbiota; hypertension treatment; hypertensive; improved; in vivo imaging; innovation; microbiota; nerve supply; nervous system disorder; neural; neural stimulation; neuromechanism; normotensive; novel; optogenetics; prevent; receptor; reduce symptoms; response; social; translational impact; translational model

Abstract Hypertension (HTN) is a prevalent cardiovascular condition and a leading risk factor for other cardiovascular diseases. If it remains untreated, HTN can lead to numerous comorbidities such as stroke, dementia, diabetes, kidney disease, obstructive sleep apnea, and neurological disorders. Despite advances in prevention and multi- drug therapy, a significant proportion of patients remain resistant or refractory to current treatments. In most cases, treatment-resistant HTN is strongly neurogenic, characterized by a dysfunctional autonomic nervous system (ANS) most recently linked to gut dysbiosis. However, mechanisms of host-microbiota interaction in HTN are not well defined. Our new preliminary data suggests that a breakdown in the neural gut-brain communication resulting from gut dysbiosis may be mediated by reduced serotonergic receptor signaling on the vagal afferent projections from the gut to the nucleus of the solitary tract. In this application, we propose to use state of the art in vivo imaging, electrophysiology and neural stimulation approaches in transgenic and humanized rats in order to interrogate specific molecular and neural mechanisms of host-microbiota interaction in health and HTN, while evaluating the potential of sub-diaphragmatic vagal stimulation for bio-electronic medicine to alleviate the symptoms of gut dysbiosis in HTN.

摘要

项目成果

Impact of exercise on brain-bone marrow interactions in chronic stress: potential mechanisms preventing stress-induced hypertension

运动对慢性应激中脑-骨髓相互作用的影响：预防应激性高血压的潜在机制

• DOI: 10.1152/physiolgenomics.00168.2022
• 发表时间: 2023
• 期刊: Physiological Genomics
• 影响因子: 4.6
• 作者: Thu Van Nguyen;Ko Yamanaka;Keisuke Tomita;Jasenka Zubcevic;Sabine S S Gouraud;Hidefumi Waki
• 通讯作者: Hidefumi Waki

Central Administration of Hydrogen Sulfide Donor NaHS Reduces Iba1-Positive Cells in the PVN and Attenuates Rodent Angiotensin II Hypertension.

• DOI: 10.3389/fnins.2021.690919
• 发表时间: 2021
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Donertas Ayaz B;Oliveira AC;Malphurs WL;Redler T;de Araujo AM;Sharma RK;Sirmagul B;Zubcevic J
• 通讯作者: Zubcevic J

Nicotine Exposure during Rodent Pregnancy Alters the Composition of Maternal Gut Microbiota and Abundance of Maternal and Amniotic Short Chain Fatty Acids.

• DOI: 10.3390/metabo12080735
• 发表时间: 2022-08-09
• 期刊: Metabolites
• 影响因子: 4.1

Small fish, big discoveries: zebrafish shed light on microbial biomarkers for neuro-immune-cardiovascular health.

• DOI: 10.3389/fphys.2023.1186645
• 发表时间: 2023
• 期刊: Frontiers in physiology
• 影响因子: 4

Central and Systemic Effects of Subdiaphragmatic Vagus Nerve Stimulation during the Development of Hypertension in the SHR.

膈下迷走神经刺激在 SHR 高血压发生过程中的中枢和系统效应。

• 发表时间: 2022
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Dirr,ElliottW;Martyniuk,ChristopherJ;Otto,KevinJ;Zubcevic,Jasenka
• 通讯作者: Zubcevic,Jasenka