Biology subjects

Monai, H.

Publications and source records attributed to Monai, H..

5 recordsLinked to original sources

bioRxiv2025

Microglia-astrocyte interaction underlies aquaporin-4 dysregulation in the mouse cortex

Brain water homeostasis relies on the coordinated actions of glial cells. In particular, astrocytes play an essential role in facilitating perivascular water exchange between cerebrospinal fluid and interstitial fluid through aquaporin-4 (AQP4), a water channel highly concentrated at astrocytic endfeet. Dysregulation of AQP4 localization is implicated in various neuropathologies, but its underlying mechanisms are unclear. Although astrocytes and microglia both express {beta}-adrenergic receptors ({beta}-AdRs), whether {beta}-AdR signaling modulates astrocytic AQP4 polarization through microglial activation has not yet been investigated. Here, we hypothesized that microglial activation mediates the {beta}-AdR-induced loss of astrocytic AQP4 polarization. To test this hypothesis, we topically applied the {beta}-AdR agonist, isoproterenol, to the primary visual cortex of anesthetized mice and evaluated AQP4 polarization using double immunohistochemistry. Acute {beta}-AdR activation (3 h) significantly reduced perivascular AQP4 polarization and enhanced local microglial reactivity. Both pharmacological inhibition of microglial activity with minocycline and microglial depletion via dietary administration of the CSF1R antagonist, PLX5622, prevented AQP4 dysregulation induced by isoproterenol. These findings demonstrate that microglial activation is required for {beta}-AdR agonist-induced AQP4 dysregulation in the mouse cortex, revealing a previously unrecognized microglia-astrocyte interaction linking adrenergic signaling to glial water homeostasis.

neuroscience↗

bioRxiv2024

Immediate glucose signaling transmitted via the vagus nerve in gut-brain neural communication

Sucrose consumption is influenced by certain gut-brain signaling mechanisms. Among these, one pathway involves neuropod cells, which form synaptic connections with the vagus nerve, leading to the immediate activation of central dopaminergic pathways. This study explored the role of the frontal cortex in its process. We found that the vagus nerves immediate activation is mediated by the sodium-glucose cotransporter 1 (SGLT1) of neuropod cells after the intragastric glucose injection in mice. Also, we showed that the involvement of both astrocytes and neurons in the frontal cortex via D2 and D1 dopamine receptors, respectively, by in vivo Ca2+ imaging. Finally, we revealed that psychological stress, which induces a reduction in sucrose preference, significantly diminishes the activation levels of both the vagus nerve and the frontal cortex. These findings highlight the role of a comprehensive gut-brain network in modulating sucrose preference, involving neuropod cells, the vagus nerve, and the frontal cortex. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/586971v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1f28baeorg.highwire.dtl.DTLVardef@b053a9org.highwire.dtl.DTLVardef@449431org.highwire.dtl.DTLVardef@5d3ad9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Transcranial direct current stimulation alters cerebrospinal fluid-interstitial fluid exchange in mouse brain

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has gained prominence recently. Clinical studies have explored tDCS as an adjunct to neurologic disease rehabilitation, with evidence suggesting its potential in modulating brain clearance mechanisms. The glymphatic system, a proposed brain waste clearance system, posits that cerebrospinal fluid-interstitial fluid (CSF-ISF) exchange aids in efficient metabolic waste removal. While some studies have linked tDCS to astrocytes inositol trisphosphate (IP3)/Ca2+ signaling, the impact of tDCS on CSF-ISF exchange dynamics remains unclear. HypothesistDCS influences the dynamics of CSF-ISF exchange through astrocytic IP3/Ca2+ signaling. MethodsIn this study, we administered tDCS (0.1mA for 10 minutes) to C57BL/6 mice anesthetized with ketamine-xylazine (KX). The anode was positioned on the cranial bone above the cortex, and the cathode was inserted into the neck. Following tDCS, we directly assessed brain fluid dynamics by injecting biotinylated dextran amine (BDA) as a CSF tracer into the cisterna magna (CM). The brain was then extracted after either 30 or 60 minutes and fixed. After 24 hours, the sectioned brain slices were stained with Alexa 594-conjugated streptavidin (SA) to visualize BDA using immunohistochemistry. We conducted Electroencephalography (EEG) recordings and aquaporin 4 (AQP4)/CD31 immunostaining to investigate the underlying mechanisms of tDCS. Additionally, we monitored the efflux of Evans blue, injected into the cisterna magna, using cervical lymph node imaging. The experiments were subsequently repeated with inositol trisphosphate receptor type 2 (IP3R2)-knockout mice. ResultsPost-tDCS, we observed an increased CSF tracer influx, indicating a modulation of CSF-ISF exchange by tDCS. Additionally, tDCS appeared to enhance the brains metabolic waste efflux. EEG recordings showed an increase in delta wave post-tDCS. But no significant change in AQP4 expression was detected 30 minutes post-tDCS. ConclusionOur findings suggest that tDCS augments the glymphatic systems influx and efflux. Through astrocyte IP3/Ca2+ signaling, tDCS was found to modify the delta wave, which correlates positively with brain clearance. This study underscores the potential of tDCS in modulating brain metabolic waste clearance.

neuroscience↗

bioRxiv2022

Spatial frequency-based correction of the spherical aberration in living brain imaging

We previously developed a fully automated spherical aberration compensation microscope system, Deep-C, to obtain spherical aberration-free images, but the contrast-based algorithm (Peak-C) may limit applications for low signal-to-noise ratio images. Herein we propose a new spatial frequency-based algorithm called Peak-F and compared its performance to Peak-C. Unlike Peak-C, Peak-F is robust to any noise level since it is independent of the dynamic range of the images, and it does not suffer from image saturation. Finally, Peak-F was implemented in a two-photon microscope to observe living aged and young mouse brains. Consequently, the average refractive index of brain tissue was higher in old mice than in young mice. The Peak-F algorithm determines high-resolution microscopic images stably and robustly.

biophysics↗

bioRxiv2020

A computationally designed fluorescent biosensor for D-serine

Solute-binding proteins (SBPs) have evolved to balance the demands of ligand affinity, thermostability and conformational change to accomplish diverse functions in small molecule transport, sensing and chemotaxis. Although the ligand-induced conformational changes that occur in SBPs make them useful components in biosensors, they are challenging targets for protein engineering and design. Here we have engineered a D-alanine-specific SBP into a fluorescent biosensor with specificity for the signaling molecule D-serine (D-serFS). This was achieved through binding site and remote mutations that improved affinity (KD = 6.7 {+/-} 0.5 M), specificity (40-fold increase vs. glycine), thermostability (Tm = 79 {degrees}C) and dynamic range (~14%). This sensor allowed measurement of physiologically relevant changes in D-serine concentration using two-photon excitation fluorescence microscopy in rat brain hippocampal slices. This work illustrates the functional trade-offs between protein dynamics, ligand affinity and thermostability, and how these must be balanced to achieve desirable activities in the engineering of complex, dynamic proteins.

biochemistry↗