Biology subjects

Thirard, S.

Publications and source records attributed to Thirard, S..

3 recordsLinked to original sources

bioRxiv2025

Dorsal Striatum Parvalbumin interneurons translatome unveiled

Parvalbumin (PV) interneurons in the dorsal striatum (DS) are fast-spiking GABAergic cells critical for feedforward inhibition and synaptic integration within basal ganglia circuits. Despite their well-characterized electrophysiological roles, their molecular identity remains incompletely defined. Using the Ribotag approach in Pvalb-Cre mice, we profiled the translatome of DS PV interneurons and identified over 2,700 transcripts significantly enriched (fold-change > 1.5) in this population. Our data validate established PV markers and reveal a distinct molecular signature of DS PV neurons compared to PV interneurons from the nucleus accumbens. Gene ontology analyses highlight prominent expression of genes related to extracellular matrix components, cell adhesion molecules, synaptic organization, ion channels, and neurotransmitter receptors, particularly those mediating glutamatergic and GABAergic signaling. Notably, perineuronal net markers were robustly expressed in DS PV interneurons and confirmed by immunofluorescence. Transcriptomic analysis of DS PV neurons following repeated d-amphetamine exposure identified Gm20683 as the only differentially expressed transcript between treated groups. Furthermore, RNAseq analysis of mice subjected to an operant behavior paradigm with two types of food reward (high-palatable diet or standard chow) identified over 1,000 and 100 genes enriched in DS PV neurons from standard and high-palatable masters, respectively. These findings provide a comprehensive molecular profile of DS PV interneurons, distinguishing them from other striatal PV populations, and reveal specific gene expression changes associated with psychostimulant exposure and reward-driven behaviors. Our findings deepen insight into the molecular mechanisms of PV interneuron activity in striatal circuits and their potential roles in neuropsychiatric, motor and reward-related disorders.

neuroscience↗

bioRxiv2025

Daily intermittent fasting is an effective multiscale treatment in preclinical models of absence epilepsy

Absence epilepsy (AE) is characterized by brief but frequent seizures with loss of consciousness. Existing treatments have heavy side effects, are only partially effective and do not address the comorbidities, including cognitive and social deficits. A tripartite link between seizures, cognitive deficits and diet has been established. We focused on intermittent fasting (IF), a regime where daily periods of fasting alternate with periods of food intake, with no restrictions in the type or quantity of food consumed. To date, the effects of IF on infantile epilepsy have not been addressed. We evaluated the therapeutic potential of a daily, one-month protocol of IF on three established mouse models of AE: the Grm7AAA KI mouse, the Scn2a haploinsufficiency mouse and the pharmacologically-induced AY-9944 mouse model. We show a reduction of the seizure frequency in all models, as well as an improvement of the sociability deficits observed in two of the models, with no adverse effects. Focusing on the Grm7AAA KI model, we performed RNA sequencing in a one of the key brain areas of the absence seizure circuit, the thalamus. We detected a deregulation of genes involved in vascularization associated with the development of malformed blood vessels in epileptic mice. Along with its anti-seizure effects, IF was able to counteract both abnormal gene expression and vessel morphology. This study demonstrates for the first time the positive effects of IF on AE and could facilitate the implementation of the diet in clinical trials.

neuroscience↗

bioRxiv2023

Tuft cell-derived acetylcholine is an effector of type 2 immunity and directly targets helminth parasites in the gut lumen

Upon parasitic helminth infection, activated intestinal tuft cells secrete IL-25, which initiates a type 2 immune response during which lamina propria ILC2s produce IL-13. This causes epithelial remodelling, including tuft cell hyperplasia with an unknown function. We describe a novel cholinergic effector function of tuft cells, which we show are the only epithelial cells expressing Choline Acetyltransferase (ChAT). During parasite infections, mice with epithelial-specific deletion of ChAT have increased worm burden and faecal egg counts although they are able to mount a comparable type 2 immune response. Mechanistically, IL-13-amplified tuft cells release acetylcholine (ACh) into the gut lumen. We demonstrate a direct effect of ACh on worms, reducing their viability and fecundity via helminth muscarinic ACh receptors, with effects promoted by inhibition of acetylcholinesterase, an helminth-secreted enzyme. Thus, tuft cells are sentinels in naive mice, and their amplification upon helminth infections serves an additional type 2 immune response effector function.

immunology↗