Biology subjects

Helyes, Z.

Publications and source records attributed to Helyes, Z..

3 recordsLinked to original sources

bioRxiv2025

Focal infrared stimulation modulates somatosensory cortical activity in mice: evidence for TRPV1 ion channel involvement

Infrared neural stimulation (INS) is a promising approach for minimally invasive modulation of neuronal activity, yet its cellular and molecular mechanisms in the intact brain remain incompletely understood. Here, we investigated focal INS in the somatosensory cortex of anesthetized mice using high-density Neuropixels recordings combined with histological analysis. Continuous-wave and pulsed (500 Hz) infrared illumination elicited robust modulation of cortical activity, with approximately half of recorded neurons exhibiting either increased or suppressed firing. The modulatory effects of stimulation were comparable across cortical layers and neuron types. While both stimulation modes were effective, continuous-wave stimulation typically produced stronger changes in firing rates and network dynamics than pulsed illumination. To explore molecular contributions, we compared responses in wild-type and TRPV1 knockout mice. Neuronal responses to INS were significantly reduced in knockout animals, indicating a key role for TRPV1 channels. We also observed layer- and neuron-type-specific differences in firing rate modulation between wild-type and knockout animals. Histological analysis confirmed that TRPV1-expressing neurons are distributed throughout cortical layers, supporting their involvement in the observed responses. These findings provide direct evidence that TRPV1 contributes to INS-evoked cortical activity and advance our understanding of the mechanisms underlying infrared neuromodulation. This work lays a foundation for the future use of infrared light as a precise and minimally invasive tool for cortical circuit manipulation.

neuroscience↗

bioRxiv2022

Hydrogen Peroxide Production by Epidermal Dual Oxidase 1 Regulates Nociceptive Sensory Signals

Keratinocytes of the mammalian skin provide not only mechanical protection for the tissues, but also transmit mechanical, chemical, and thermal stimuli from the external environment to the sensory nerve terminals. Sensory nerve fibers penetrate the epidermal basement membrane and function in the tight intercellular space among keratinocytes. Here we show that epidermal keratinocytes produce hydrogen peroxide upon the activation of the NADPH oxidase dual oxidase 1 (DUOX1). This enzyme can be activated by increasing cytosolic calcium levels. Using DUOX1 knockout animals as a model system we found an increased sensitivity towards certain noxious stimuli in DUOX1-deficient animals, which is not due to structural changes in the skin as evidenced by detailed immunohistochemical and electron-microscopic analysis of epidermal tissue. We show that DUOX1 is expressed in keratinocytes but not in the neural sensory pathway. The release of hydrogen peroxide by activated DUOX1 alters both the activity of neuronal TRPA1 and redox-sensitive potassium channels expressed in dorsal root ganglia primary sensory neurons. We describe hydrogen peroxide, produced by DUOX1 as a paracrine mediator of nociceptive signal transmission. Our results indicate that a novel, hitherto unknown redox mechanism modulates noxious sensory signals.

physiology↗

bioRxiv2020

The Anti-histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits SARS-CoV-2 Infection in Reconstituted Human Nasal Tissue In Vitro

BackgroundThe COVID-19 pandemic is an enormous threat for healthcare systems and economies worldwide that urgently demands effective preventive and therapeutic strategies. Unlike the development of vaccines and new drugs specifically targeting SARS-CoV-2, repurposing of approved or clinically tested drugs can provide an immediate solution. MethodsWe applied a novel computational approach to search among approved and clinically tested drugs from the DrugBank database. Candidates were selected based on Shannon entropy homology and predefined activity profiles of three small molecules with proven anti-SARS-CoV activity and a published data set. Antiviral activity of a predicted drug, azelastine, was tested in vitro in SARS-CoV-2 infection assays with Vero E6 monkey kidney epithelial cells and reconstituted human nasal tissue. The effect on viral replication was assessed by quantification of viral genomes by droplet digital PCR. FindingsThe computational approach with four independent queries identified major drug families, most often and in overlapping fashion anti-infective, anti-inflammatory, anti-hypertensive, anti-histamine and neuroactive drugs. Azelastine, an histamine 1 receptor-blocker, was predicted in multiple screens, and based on its attractive safety profile and availability in nasal formulation, was selected for experimental testing. Azelastine significantly reduced cytopathic effect and SARS-CoV-2 infection of Vero E6 cells with an EC50 of [~]6 M both in a preventive and treatment setting. Furthermore, azelastine in a commercially available nasal spray tested at 5-fold dilution was highly potent in inhibiting viral propagation in SARS-CoV-2 infected reconstituted human nasal tissue. InterpretationsAzelastine, an anti-histamine, available in nasal sprays developed against allergic rhinitis may be considered as a topical prevention or treatment of nasal colonization with SARS-CoV-2. As such, it could be useful in reducing viral spread and prophylaxis of COVID-19. Ultimately, its potential benefit should be proven in clinical studies. Fundingprovided by the Hungarian government to the National Laboratory of Virology and by CEBINA GmbH.

microbiology↗