Biology subjects

Langlois, L.

Publications and source records attributed to Langlois, L..

4 recordsLinked to original sources

bioRxiv2026

Chronic Activity-Based Anorexia triggers a glial response in the hippocampus independent of intestinal epithelial Toll-Like Receptor 4

Anorexia nervosa is characterized by maladaptive eating behavior and cognitive dysfunction, which could be explained by a neuroinflammation. A gut dysbiosis could link gastrointestinal alterations to central dysfunctions, particularly via the toll-like receptor 4 (TLR4), which has been shown to play a key role in the activity-based anorexia (ABA) model. We aimed to evaluate the neuroinflammation and its behavioral consequences in the ABA model, and to decipher the role of the microbiota-gut-brain axis, and more specifically of TLR4, in these alterations of the central nervous system. We show that chronic restriction is more strongly associated with gut inflammation, cecal microbiota alteration and neuroinflammatory processes in the hippocampus than acute restriction. The hippocampal glial response is characterized by a loss of astrocyte density, and an increased number of deramified microglia. We further demonstrate that these alterations are independent of TLR4 expressed by intestinal epithelial cells. In conclusion, our results highlight that the chronicity of ABA-associated undernutrition alters the response of glial cells in the hippocampus that is linked with changes in microbiota composition, highlighting the importance of faster diagnosis and treatment of AN.

neuroscience↗

bioRxiv2025

Glutamine alters the response to stress in mice with diet-induced obesity in a sex-dependent manner.

RationalePatients with class III obesity often suffer from irritable bowel syndrome (IBS) while obesity and IBS share common pathophysiological mechanisms such as altered intestinal barrier function and gut microbiota dysbiosis. Oral glutamine (Gln) supplementation previously showed beneficial effects on gut barrier function in a sex-dependent manner and reduced abdominal pain in IBS patients. Thus, we assessed the sex-dependent response to an oral Gln supplementation in mice with diet-induced obesity and subjected to a chronic restraint stress to mimic IBS. MethodsMale (M) and female (F) C57BL/6 mice received a high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14) and were subjected or not to a restraint stress (S) for the 4 last days. From W12, mice received or not Gln in drinking water (2g/kg/day; n=12/group). Plasma corticosterone, body composition, glucose tolerance (OGTT), intestinal permeability, inflammatory markers in colonic and white adipose tissues, cecal microbiota and short-chain fatty acid (SCFA) composition have been assessed. Within each sex, groups were compared by Kruskal-Wallis test or a 1-way ANOVA test. ResultsIn M-HFD mice, chronic restraint stress was associated with a better glucose tolerance (-15,46% AUC) and a reduced fasting glycemia that was not observed in F-HFD mice. Gln partially prevented body weight loss, reduced plasma resistin, plasma corticosterone and colonic permeability in female stressed obese mice. In male stressed obese mice, Gln limited lean mass loss, reduced colonic permeability and Ccl2 mRNA level in the subcutaneous adipose tissue. Chronic restraint stress and Gln modified cecal microbiota in both sexes but cecal SCFA composition only in male mice. In particular, stress induced an increased abundance of Pseudomonadota in male mice that was partially restored after Gln supplementation. In addition, cecal total SCFA were reduced in Gln-supplemented stressed HFD male mice compared to unstressed HFD mice. In female HFD mice, stress associated to Gln supplementation increased the abundance of Thermodesulfobacteriota and reduced colonic expression of Cxcr3 mRNA. ConclusionsChronic restraint stress has beneficial effects on glycemia control in male HFD mice without additive effects of Gln supplementation. By contrast, Gln reduces stress-induced corticosterone level and body weight loss only in females. These data, as well as the differential impact of Gln on intestinal permeability and gut microbiota according to the sex, deserves further investigations to decipher the underlying mechanisms.

pathology↗

bioRxiv2025

Sex-dependent effects of intestinal epithelial TLR4 deletion induced before activity-based anorexia

RationaleA role for the microbiota-gut-brain axis in the pathophysiology of anorexia nervosa (AN) has emerged in the last decade. An alteration of intestinal Toll-like receptor type 4 (TLR4) has been reported in the activity-based anorexia (ABA) model with an increase in its expression at the cell surface of colonic epithelial cells. In addition, inducible TLR4 invalidation in intestinal epithelial cells (IECs) was associated with behavioral and energy balance changes in ABA mice. The aim of this study was to assess the intestinal response, e.g. inflammation, gut barrier function and gut microbiota composition, to TLR4 invalidation in IEC in ABA mice. MethodsMale and female Villin-CreERT2-TLR4 LoxP C57Bl/6 mice were injected with tamoxifen to induce a specific invalidation of TLR4 in IECs (TLR4IEC-/- mice). Then, wild-type (wt) and TLR4IEC-/- mice were subjected or not to the ABA protocol which combines an access to a running wheel and a progressively limited access to food. After 12 days, colon samples were collected and the expression of 44 mRNAs encoding proteins involved in inflammatory response, gut barrier function and homeostatic regulation was measured by qPCR. Results were compared by a two-way ANOVA (ABA x TLR4IEC-/-). Gut microbiota composition was analysed by 16S rRNA Illumina sequencing. ResultsIn both male and female ABA TLR4IEC-/- mice, the kinetics of body weight loss was slowed down. In addition, male and female ABA TLR4IEC-/- mice showed an increase and a decrease in food intake, respectively. In males, TLR4 invalidation in IEC was associated with a reduction of Tlr2, Ticam1, Myd88, Tnf, I{kappa}B, Irf3, Cxcr3 and Tgf{beta} mRNA expression and fecal calprotectin levels under control conditions but not in response to the ABA model. In females, Myd88, Il6, Cxcl1 and Ccl2 mRNA levels were increased by TLR4IEC invalidation in control mice but not in ABA, except for Ccl2. TLR4 invalidation also affected the expression of genes involved in gut barrier function in control and ABA mice in a sex-dependent manner. Male mice exhibited more marked alterations. For instance, male CT TLR4IEC-/- showed a decrease of numerous targets (Ocln, Marveld2, F11r, Tjp1, Cldn7, Cldn12, Cldn15). ABA TLR4IEC-/- mice did not exhibit this decrease but other changes were observed such as an increase in Cldn3 and Cldn7 mRNA levels. Finally, TLR4IEC invalidation in control mice, but not in ABA, altered the gut microbiota in a sex dependent manner with an increase in the abundance of Parasutterella and Desulfovibrio genera in females and males, respectively. Interestingly, the ABA model per se induced an increase in the abundance of the Lactobacillus genus in both sexes, which was not observed in ABA TLR4IEC-/-. ConclusionsOur study shows for the first time the impact of inducible TLR4 invalidation in IEC on the intestinal response. We highlighted numerous colonic alterations regarding epithelial permeability, mucosal inflammation and gut microbiota composition, in control and ABA conditions: all were partially reversed in ABA TLR4IEC-/-. TLR4 invalidation in IEC also induced changes in energy homeostasis in response to the ABA model both in female and male mice. Further studies are warranted to deeply evaluate the underlying mechanisms.

physiology↗

bioRxiv2019

Atrx deletion in neurons leads to sexually-dimorphic dysregulation of miR-137 and spatial learning and memory deficits

Mutations in the ATRX chromatin remodeler are associated with syndromic and non-syndromic intellectual disability. Emerging evidence points to key roles for ATRX in preserving neuroprogenitor cell genomic stability, whereas ATRX function in differentiated neurons and memory processes are still unresolved. Here, we show that Atrx deletion in mouse forebrain glutamatergic neurons causes distinct hippocampal structural defects identified by magnetic resonance imaging. Ultrastructural analysis revealed fewer presynaptic vesicles and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. These synaptic defects are associated with impaired long-term contextual memory in male, but not female mice. Mechanistically, we identify ATRX-dependent and sex-specific alterations in synaptic gene expression linked to Mir137 levels, a known regulator of presynaptic processes and spatial memory. We conclude that ablation of Atrx in excitatory forebrain neurons leads to sexually dimorphic outcomes on miR-137 and on spatial memory, identifying a promising therapeutic target for neurological disorders caused by ATRX dysfunction.\n\nSummary statementAblation of the ATRX chromatin remodeler specifically in forebrain excitatory neurons of mice causes male-specific deficits in long-term spatial memory associated with miR-137 overexpression, transcriptional changes and structural alterations corresponding to pre- and post-synaptic abnormalities.

neuroscience↗