Biology subjects

Gauvrit, T.

Publications and source records attributed to Gauvrit, T..

3 recordsLinked to original sources

bioRxiv2025

A cluster of three snoRNAs including jouvence required in the gut determines lifespan and confers neuroprotection through metabolic parameters

In our society, the aging of the population is a major concern of public health. Recently we have identified a new snoRNA (jouvence) in Drosophila, and showed that its deletion (F4) reduces lifespan, while its overexpression increases it. F4 deleted flies also present neurodegenerative lesions and a deregulation of metabolic parameters as triglycerides and sterol. However, a deeper characterization of this genomic locus has revealed the presence of two other snoRNAs. Here, we have characterized at the whole organismal level, the role of each them. First, we show that each snoRNAs are expressed in the epithelium of the gut (enterocytes), and in the fat body. Second, in F4 deletion, the re-expression of each snoRNA in the enterocytes or in the fat body is sufficient to improve lifespan, and protect against neurodegeneration in old flies. In addition, depending of the snoRNAs, it rescues the expression of specific deregulated genes within the epithelium of the gut, involved in lipids and sterol metabolism. Consequently, these two metabolic parameters are also rescued, establishing a relationship between the lesions of the brain, the metabolic disorders, the lifespan, and each snoRNAs respectively. Finally, histological stainings as Nile Red and BODIPY C11-581/591 have revealed that the neurodegenerative lesions are due to an increase of free sterol within the brain, and lipid peroxydation in the pericerebral fat body. Altogether, these results point-out a causal relationship between the epithelium of the gut and the neurodegenerative lesions through the metabolic parameters, indicating a gut-brain axis.

neuroscience↗

bioRxiv2025

Sex-dependent effects of maternal high-fat diet during lactation in adult THY-Tau22 mice offspring

The perinatal environment has been suggested to participate to the development of tauopathies and Alzheimers disease but the molecular and cellular mechanisms involved remain contradictory and under-investigated. Here, we evaluated the effects of a maternal high-fat diet (HFD) during lactation on the development of tauopathy in the THY-Tau22 mouse strain, a model of progressive tau pathology associated with cognitive decline. During lactation, dams were fed either a chow diet (13.6% of fat) or a HFD (58% of fat). At weaning, offspring was fed a chow diet until sacrifice at 4 months of age (the onset of tau pathology) or 7 months of age (the onset of cognitive impairment). During lactation, maternal HFD increased body weight gain in offspring. At 3 months of age, maternal HFD led to a mild glucose intolerance only in male offspring. Moreover, it impaired spatial memory in both male and female 6-month-old offspring, with males being more impacted. These cognitive deficits were associated with increased phosphorylation of hippocampal tau protein-observed at 4 months in males and at 7 months in females, highlighting a sex-specific temporal shift. Additionally, maternal HFD modified adult hippocampal neurogenesis (AHN), leading to an increase of mature neuronal cells number in females and of dendritic arborization length in males. Synaptic analysis further revealed that maternal HFD led to synaptic loss only in males. Finally, multi-omics approaches showed that maternal HFD has long-term consequences on both transcriptome, proteome and regulome, this effect being also sex-dependent with mitochondrial pathways, ribosomal activity, cilium and the extracellular matrix predominantly impacted in males, while gliogenesis, myelination and synaptic plasticity were primarily affected in females. Regulome analysis suggested that this sex-dependent phenotype was more related to a temporal shift rather than distinct sex-specific alterations. Collectively, our data suggest that maternal malnutrition accelerates the development of tauopathy in THY-Tau22 offspring, with sex-dependent effects, males being impacted earlier than females. These findings highlight the critical role of the perinatal environment as a key window of opportunity for interventions aimed at preventing the development of neurodegenerative diseases.

neuroscience↗

bioRxiv2024

Disrupted stimulus encoding shapes tactile perception in autism.

Touch is essential for interacting with the world, and atypical tactile experience is a core feature of autism that profoundly affects daily life. However, we do not know the neural mechanisms of low-level tactile perception and their alterations in autism. Using a translational perceptual task, we recapitulate the multifaceted tactile features of autistic individuals in the Fmr1-/y mouse model of autism, showing tactile hyposensitivity, interindividual variability, and unreliable responses. We reveal that impaired detection decoding in Fmr1-/y-hyposensitive mice stems from diminished single-neuron signal-to-noise ratio in the primary somatosensory cortex that leads to weak population encoding of the tactile stimulus and its detection. This manifests as reduced stimulus-dependent neural recruitment, impaired response precision, and disrupted ensemble dynamics. Decreasing neuronal hyperexcitability strengthens sensory encoding and improves tactile perception. This work provides a translational framework for probing neuronal-perceptual changes in neurodevelopmental conditions, reveals inter-individual variability in preclinical models, and uncovers the neural basis of tactile hyposensitivity in autism.

neuroscience↗