Biology subjects

Chevillard, P.-M.

Publications and source records attributed to Chevillard, P.-M..

4 recordsLinked to original sources

bioRxiv2025

Microglia regulate neuronal activity via structural remodeling of astrocytes

Neuron-glia interactions play a central role in regulating synaptic transmission and neuronal excitability. Structural plasticity of astrocytes is associated with numerous physiological and pathological conditions, however, the mechanism underlying this process remains unknown. To examine the basis for structural astrocyte plasticity, we used the classic example of the loss of astrocytic processes that takes place in the hypothalamic magnocellular system during chronic high-salt intake. We discovered that a high-salt diet triggers a local accumulation of reactive microglia around vasopressin-secreting neurons, but not in other brain areas. Microglia phagocytose astrocytic processes, reducing astrocytic coverage of vasopressin neurons. The pruning of astrocytic processes impairs synaptic glutamate clearance, enabling activation of extrasynaptic glutamate NMDA receptors and increasing the activity of vasopressin neurons. Inhibiting microglia-mediated astrocyte pruning attenuates the increased neuronal activity and vasopressin-dependent hypertensive phenotype of rats fed high-salt diet. Thus, microglia orchestrate neuron-glia interactions and regulate neuronal activity through astrocyte pruning.

neuroscience↗

bioRxiv2022

1H-MRS characterization of metabolic changes induced by photoperiod in the sheep brain: a promising eye into in-vivo adult neurogenesis?

The hypothalamus is a central structure of the mammalian brain, which controls physiological, endocrine and metabolic brain homeostasis. Despite this essential role, little is known about the normal and altered neurochemical changes occurring within the hypothalamic structures. Here, the metabolism of the hypothalamus of ewes was investigated at 3T using proton magnetic resonance spectroscopy (1H-MRS). We used the sensitivity of these animals to photoperiod i.e. the ratio of day to night length, to investigate the hypothalamic metabolic changes and their relationship to hypothalamic adult neurogenesis. A longitudinal study involving 4 ewes per timepoint was conducted at 4 time points (P01, P02, P03 and P04) during long days (LD) and 4 time points during short days (SD). Significant metabolic changes were found between LD and SD at all time points in particular for glutamate (Glu), glutamine, myo-inositol and total N-acetyl-Aspartate (NAA). During SD, glutamate and glutamine concentrations were significantly smaller at P01 compared to all other time points while significant neurochemical changes occurred during the entire LD period. Neurochemical changes relative to P01 remained stable during LD and SD except for Glu and Gln which increased between P01 and P02 during SD. Relative metabolic changes were significantly higher on average for NAA and Glu and significantly smaller on average for total choline during SD compared to LD, respectively, paralleling the average changes in the numbers of neural stem cells and glial and oligodendrocyte progenitors found by immunohistochemistry. Despite important differences between MRS and immunohistochemistry in terms of spatial resolution, both techniques suggest complementary findings that should contribute to a better characterization of the hypothalamus during photoperiodism and adult neurogenesis. We conclude that 1H-MRS could be a promising non-invasive translational technique to investigate the existence of adult neurogenesis in-vivo in gyrencephalic brains.

neuroscience↗

bioRxiv2020

The sheep brain: an interesting translational model for functional MRI studies?

Biomedical investigations in clinically relevant animal models is of crucial interest for faster and appropriate transfer to human. The ovine model has already demonstrated its potential compared to rodents and non-human primates (NHP) in various studies: sheep possess a gyrencephalic brain, captivity is not an issue and can undergo magnetic resonance imaging (MRI) in routine clinical scanners (1.5T, 3T) under identical conditions using similar techniques to humans. To date, the effects of anesthesia have been poorly explored and only few functional MRI (fMRI) studies were conducted in sheep. Here, Blood Oxygen Level dependent fMRI and perfusion MRI were conducted in lambs and adult ewes at 3 T. Robust but weak BOLD responses to visual stimulation were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. BOLD responses were weaker in adult sheep than in lambs while relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher in lambs than in adult sheep for both gray and white matter in accordance with previous findings in the human. Assessment of functional responses in healthy individuals under adequate physiological conditions is essential for robust translational studies.

neuroscience↗

bioRxiv2020

Proteomic and functional mapping of cardiac NaV1.5 channel phosphorylation reveals multisite regulation of surface expression and gating

Phosphorylation of NaV1.5 channels regulates cardiac excitability, yet the phosphorylation sites regulating channel function and the underlying mechanisms remain largely unknown. Using a systematic quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from non-failing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines-664 and -667 regulate the voltage-dependence of channel activation in a cumulative manner, whereas phosphorylation of the nearby serine-671, which is increased in failing hearts, decreases cell surface NaV1.5 expression and peak Na+ current. No additional roles could be assigned to the other clusters of phosphosites. Taken together, the results demonstrate that ventricular NaV1.5 is highly phosphorylated, and that the phosphorylation-dependent regulation of NaV1.5-encoded channels is highly complex, site-specific and dynamic. AbbreviationsA, alanine; E, glutamate; HEK-293, Human Embryonic Kidney 293 cells; INa, peak Na+ current; INaL, late Na+ current; IP, immunoprecipitation; mNaVPAN, anti-NaV channel subunit mouse monoclonal antibody; MS, Mass Spectrometry; MS1, mass spectrum of peptide precursors; MS2 or MS/MS, fragmentation mass spectrum of peptides selected in narrow mass range (2 Da) from MS1 scan; NaV, voltage-gated Na+ channel; pS, phosphoserine; pT, phosphothreonine; S, serine; T, threonine; TAC, Transverse Aortic Constriction; TMT, Tandem Mass Tag.

physiology↗