Biology subjects

Vialou, V.

Publications and source records attributed to Vialou, V..

3 recordsLinked to original sources

bioRxiv2023

Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood. We report that astrocyte aquaporin 4 (AQP4) mediates a tonic water efflux in basal conditions. Acute inhibition of astrocyte AQP4 leads to intracellular water accumulation as optically resolved by fluorescence-translated imaging in acute brain slices, and in vivo by fiber photometry in mobile mice. We then show that aquaporin-mediated constant water efflux maintains astrocyte volume and osmotic equilibrium, astrocyte and neuron Ca2+ signaling, and extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance imaging (DW-MRI), we observed that in vivo inhibition of AQP4 water efflux heterogeneously disturbs brain water homeostasis in a region-dependent manner. Our data suggest that astrocyte aquaporin, though bidirectional in nature, mediates a tonic water outflow to sustain cellular and environmental equilibrium in brain parenchyma. Significance statementOur brain is immersed, thus protected, in a water environment. It ensures intra- and extracellular molecular diffusion, which is vital for brain function and health. Brain water homeostasis is maintained by dynamic water transport between different cell types. Astrocytes are a main type of glial cell widely distributed in brain parenchyma, expressing the bidirectional aquaporin water channel. Here we show that in basal conditions, aquaporin channel mediates a tonic water efflux from astrocytes. This mechanism maintains astrocyte volume stability, activity-gated brain parenchyma remodeling and brain water homeostasis. Our finding sheds light on how astrocytes regulate water states in the brain, and will help to understand brain allostasis in specific life contexts.

physiology↗

bioRxiv2023

Astrocytes control cocaine-induced synaptic plasticity and reward through the matricellular protein hevin

Drug addiction involves profound modifications of neuronal plasticity in the nucleus accumbens, which may engage various cell types. Here, we report prominent effects of cocaine on calcium signals in astrocytes characterized by in vivo fiber photometry. Astrocyte calcium signals in the nucleus accumbens are sufficient and necessary for the acquisition of cocaine seeking behavior. We identify the astrocyte-secreted matricellular protein hevin as an effector of the action of cocaine and calcium signals on reward and neuronal plasticity.

neuroscience↗

bioRxiv2023

Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain

Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contributes to the effects of SSRI by regulating the routing of the essential amino acid tryptophan to the brain. Contrarily to wild-type mice, OCT2-invalidated mice failed to respond to prolonged fluoxetine treatment in a chronic depression model induced by corticosterone exposure recapitulating core symptoms of depression, i.e., anhedonia, social withdrawal, anxiety, and memory impairment. After corticosterone and fluoxetine treatment, the levels of tryptophan and its metabolites serotonin and kynurenine were decreased in the brain of OCT2 mutant mice compared to wild-type mice and reciprocally tryptophan and kynurenine levels were increased in mutants plasma. OCT2 was detected by immunofluorescence in several structures at the blood-cerebrospinal fluid (CSF) or brain-CSF interface. Tryptophan supplementation during fluoxetine treatment increased brain concentrations of tryptophan in wild-type and OCT2 mutant mice, yet more efficiently in WT than in mutants, while discretely increasing 5-HT concentrations. Importantly, tryptophan supplementation improved the sensitivity to fluoxetine treatment of OCT2 mutant mice, impacting chiefly anhedonia and short-term memory. Western blot analysis showed that glycogen synthase kinase-3{beta} (GSK3{beta}) and mammalian/mechanistic target of rapamycin (mTOR) intracellular signaling was impaired in OCT2 mutant mice brain after corticosterone and fluoxetine treatment and, conversely, tryptophan supplementation recruited selectively the mTOR protein complex 2. This study provides the first evidence of the physiological relevance of OCT2-mediated tryptophan transport, and its biological consequences on serotonin homeostasis in the brain and SSRI efficacy.

neuroscience↗