Ion-tunable antiambipolarity in mixed ion–electron conducting polymers enables biorealistic organic electrochemical neurons

Nature Materials, Journal Year: 2023, Volume and Issue: 22(2), P. 242 - 248

Published: Jan. 12, 2023

Biointegrated neuromorphic hardware holds promise for new protocols to record/regulate signalling in biological systems. Making such artificial neural circuits successful requires minimal device/circuit complexity and ion-based operating mechanisms akin those found biology. Artificial spiking neurons, based on silicon-based complementary metal-oxide semiconductors or negative differential resistance device circuits, can emulate several features but are complicated fabricate, not biocompatible lack ion-/chemical-based modulation features. Here we report a biorealistic conductance-based organic electrochemical neuron (c-OECN) using mixed ion-electron conducting ladder-type polymer with stable ion-tunable antiambipolarity. The latter is used the activation/inactivation of sodium channels delayed activation potassium neurons. These c-OECNs spike at bioplausible frequencies nearing 100 Hz, most critical features, demonstrate stochastic enable neurotransmitter-/amino acid-/ion-based modulation, which then stimulate nerves vivo. combined impossible achieve previous technologies.

Language: Английский

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Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(6), P. 892 - 904

Published: June 22, 2023

Abstract Progress in understanding brain–viscera interoceptive signaling is hindered by a dearth of implantable devices suitable for probing both brain and peripheral organ neurophysiology during behavior. Here we describe multifunctional neural interfaces that combine the scalability mechanical versatility thermally drawn polymer-based fibers with sophistication microelectronic chips organs as diverse gut. Our approach uses meters-long continuous can integrate light sources, electrodes, thermal sensors microfluidic channels miniature footprint. Paired custom-fabricated control modules, wirelessly deliver optogenetics transfer data physiological recording. We validate this technology modulating mesolimbic reward pathway mouse brain. then apply anatomically challenging intestinal lumen demonstrate wireless sensory epithelial cells guide feeding behaviors. Finally, show optogenetic stimulation vagal afferents from sufficient to evoke phenotype untethered mice.

Language: Английский

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Bioelectronic Medicine: a multidisciplinary roadmap from biophysics to precision therapies

Frontiers in Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 19, 2024

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation nervous system by precise delivery electrical current for treatment conditions, such post-stroke movement recovery or drug-resistant disorders. The unquestionable impact is underscored successful translation to humans in last decades, long list preclinical studies. Given emergency accelerating progress new neuromodulation treatments (i.e., hypertension, autoimmune degenerative diseases), collaboration between multiple fields imperative. This work intends foster multidisciplinary bring together different provide fundamental basis underlying Medicine. In this review we will go from biophysics cell membrane, which consider inner core neuromodulation, patient care. We discuss recently discovered mechanism neurotransmission switching how it design, update on neuronal glial health disease. advances biomedical technology have facilitated collection large amounts data, thereby introducing challenges data analysis. approaches high throughput analysis, encompassing big networks, artificial intelligence, internet things. Emphasis be placed understanding electrochemical properties neural interfaces, along with integration biocompatible reliable materials compliance regulations translational applications. Preclinical validation foundational process, critical aspects animal Finally, focus point-of-care ultimate goal bioelectronic medicine. a call scientists common endeavor: accelerate decoding era therapeutic possibilities.

Language: Английский

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Chronic Stress and Headaches: The Role of the HPA Axis and Autonomic Nervous System

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 463 - 463

Published: Feb. 13, 2025

Chronic stress significantly influences the pathogenesis of headache disorders, affecting millions worldwide. This review explores intricate relationship between and headaches, focusing on dysregulation hypothalamic-pituitary-adrenal (HPA) axis autonomic nervous system (ANS). Persistent could lead to neuroinflammation, increased pain sensitivity, vascular changes that contribute development progression. The bidirectional nature this creates a vicious cycle, with recurrent headaches becoming source additional stress. Dysregulation HPA ANS imbalance amplify susceptibility intensifying their frequency severity. While pharmacological interventions remain common, non-pharmacological approaches targeting reduction, such as cognitive-behavioral therapy, biofeedback, relaxation techniques, offer promising avenues for comprehensive management. By addressing underlying stress-related mechanisms, these provide sustainable strategy reduce improve patients' quality life.

Language: Английский

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Neuroinflammation through the vagus nerve-dependent gut–microbiota–brain axis in treatment-resistant depression

Progress in brain research, Journal Year: 2023, Volume and Issue: unknown, P. 61 - 77

Published: Jan. 1, 2023

Language: Английский

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B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract The rapid onset of innate immune defenses is critical for early control viral replication in an infected host and yet it can also lead to irreversible tissue damage, especially the respiratory tract. Sensitive regulators must exist that modulate inflammation, while controlling infection. In present study, we identified acetylcholine (ACh)-producing B cells as such regulators. are most prevalent ACh-producing leukocyte population tract demonstrated with choline acetyltransferase (ChAT)-green fluorescent protein (GFP) reporter mice, both before after infection influenza A virus. Mice lacking ChAT cells, disabling their ability generate ACh (ChatBKO), but not those T significantly, selectively directly suppressed α7-nicotinic-ACh receptor-expressing interstitial, alveolar, macrophage activation secrete tumor necrosis factor (TNF), better virus at 1 d postinfection. Conversely, TNF blockade via monoclonal antibody treatment increased loads time. By day 10 infection, ChatBKO mice showed local systemic inflammation reduced signs lung epithelial repair despite similar clearance. Thus, key participants immediate regulatory cascade controls damage shifting balance toward cost enhanced replication.

Language: Английский

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Cholinergic signaling via the α7 nicotinic acetylcholine receptor regulates the migration of monocyte-derived macrophages during acute inflammation

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 4, 2024

The involvement of the autonomic nervous system in regulation inflammation is an emerging concept with significant potential for clinical applications. Recent studies demonstrate that stimulating vagus nerve activates cholinergic anti-inflammatory pathway inhibits pro-inflammatory cytokines and controls inflammation. α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages plays a key role mediating effects through downstream intracellular mechanism involving inhibition NF-κB signaling, which results suppression cytokine production. However, α7nAChR other aspects immune response, including recruitment monocytes/macrophages to site remained poorly understood. We observed increased mortality α7nAChR-deficient mice (compared wild-type controls) endotoxemia, was paralleled reduction number monocyte-derived lungs. Corroborating these results, fluorescently labeled monocytes adoptively transferred WT showed significantly diminished inflamed tissue. deficiency did not affect monocyte 2D transmigration across endothelial monolayer, but it decreased migration 3D fibrin matrix. In vitro analysis major adhesive receptors (L-selectin, β1 β2 integrins) chemokine (CCR2 CCR5) revealed reduced expression integrin αM αX macrophages. Decreased αMβ2 confirmed labeled, lungs endotoxemic mice, indicating α7nAChR-mediated migration. novel macrophage tissue, indicates important new aspect responses

Language: Английский

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Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 120, P. 630 - 639

Published: April 24, 2024

Language: Английский

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Morphoceuticals: Perspectives for discovery of drugs targeting anatomical control mechanisms in regenerative medicine, cancer and aging

Drug Discovery Today, Journal Year: 2023, Volume and Issue: 28(6), P. 103585 - 103585

Published: April 12, 2023

Morphoceuticals are a new class of interventions that target the setpoints anatomical homeostasis for efficient, modular control growth and form. Here, we focus on subclass: electroceuticals, which specifically cellular bioelectrical interface. Cellular collectives in all tissues form networks via ion channels gap junctions process morphogenetic information, controlling gene expression allowing cell to adaptively dynamically pattern formation. Recent progress understanding this physiological system, including predictive computational models, suggests targeting interfaces can embryogenesis maintain shape against injury, senescence tumorigenesis. We propose roadmap drug discovery focused manipulating endogenous bioelectric signaling regenerative medicine, cancer suppression antiaging therapeutics.

Language: Английский

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Repeated use of 3,4-methylenedioxymethamphetamine is associated with the resilience in mice after chronic social defeat stress: A role of gut–microbiota–brain axis

Psychiatry Research, Journal Year: 2022, Volume and Issue: 320, P. 115020 - 115020

Published: Dec. 21, 2022

3,4-Methylenedioxymethamphetamine (MDMA), the most widely used illicit compound worldwide, is attractive therapeutic drug for post-traumatic stress disorder (PTSD). Recent observational studies of US adults demonstrated that lifetime MDMA use was associated with lower risk depression. Here, we examined whether repeated administration can affect resilience versus susceptibility in mice exposed to chronic social defeat (CSDS). CSDS produced splenomegaly, anhedonia-like phenotype, and higher plasma levels interleukin-6 (IL-6) saline-treated mice. In contrast, did not cause these changes MDMA-treated Analysis gut microbiome found several microbes altered between saline + group group. Untargeted metabolomics analysis showed N-epsilon-methyl-L-lysine were significantly than those control groups. Interestingly, there positive correlations IL-6 abundance (or N-epsilon-methyl-L-lysine) three Furthermore, also conclusion, data suggest might contribute subjected through gut–microbiota–brain axis.

Language: Английский

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