Biology subjects

Tognini, P.

Publications and source records attributed to Tognini, P..

7 recordsLinked to original sources

bioRxiv2026

The Critical Period Microbiota Shape Brain Plasticity

The gut microbiota is increasingly recognized as a regulator of brain function, yet its role in experience-dependent plasticity during postnatal development remains largely unknown. Here, we show that disrupting the gut microbiota with antibiotics during critical periods of visual cortex development impairs ocular dominance plasticity (ODP) in juvenile mice. Antibiotic treatment induces marked changes in microbial community composition and is accompanied by extensive transcriptional remodeling of the visual cortex, including pathways involved in extracellular matrix organization, blood-brain barrier function, and myelination. Remarkably, fecal transplantation of the juvenile microbiota into adult recipients restores ODP. These findings identify the gut microbiota as a previously unrecognized regulator of neurodevelopmental plasticity and support the existence of microbiota-dependent critical periods of brain development. More broadly, our results suggest that early-life microbial perturbations may have lasting consequences for lifelong brain function and reveal that juvenile microbiota-derived signals could be exploited to promote plasticity in the adult brain.

neuroscience↗

bioRxiv2025

Succinate Modulation as a Novel Mechanism Underlying the Effects of Intermittent Fasting on Brain Function and Metabolism in Diet-Induced Obesity

Obesity significantly impacts the central nervous system (CNS), increasing risks of neuropsychiatric disorders and dementia. Intermittent fasting (IF) shows promise for improving peripheral and CNS health, but its mechanisms are unclear. Using a diet-induced obesity mouse model (10 weeks high fat diet (HFD), then 4 weeks intervention), we compared HFD, HFD-IF, ad libitum control chow (CC), and CC-IF groups. Switching to CC or IF reduced body weight, fat mass, and improved glucose tolerance. Notably, CC-IF uniquely enhanced exploration and reduced anxiety-like behavior. Transcriptomics revealed HFD-induced hippocampal neuroinflammation, while metabolomics identified a specific succinate signature in CC-IF mice: plasma concentration decreased while liver and brown adipose tissue (BAT) levels increased. Succinate supplementation mimicked CC-IF metabolic and behavioral benefits and reduced hippocampal inflammation. These findings suggest that regulating plasma succinate and its metabolism in liver and BAT may represent a novel mechanism underlying the metabolic, neuroinflammatory, and behavioral improvements induced by IF.

neuroscience↗

bioRxiv2024

Multi-Site Investigation of Gut Microbiota in CDKL5 Deficiency Disorder Mouse Models: Targeting Dysbiosis to Improve Neurological Outcomes

BackgroundCyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) is a rare X-linked developmental encephalopathy caused by pathogenic variants of the CDKL5 gene. In addition to a diverse range of neurological symptoms, CDD patients frequently manifest gastrointestinal (GI) issues and subclinical immune dysregulation. This comorbidity suggests a potential association with the intestinal microbiota, prompting an investigation into whether gut dysbiosis contributes to the severity of both GI and neurological symptoms. MethodsWe examined the gut microbiota composition in two CDKL5 null (KO) mouse models in males at three different developmental stages: postnatal day (P) 25 and P32 during youth, and P70 during adulthood. ResultsChanges in diversity and composition were observed, particularly during juvenile ages, suggesting a potential gut microbiota dysbiosis in the CDD mouse models. To further understand the role of the gut microbiota in CDD, we administered an antibiotic cocktail to the mice and conducted functional and behavioral assessments. Remarkably, significant improvement in visual cortical responses and reductions in hyperactive behavior were observed. To shed light on the cellular mechanisms we focused on microglia. Alterations in specific aspects of microglia morphology, indicative of activation state and surveillance of the microenvironment, were observed in the CDKL5 KO mice and ameliorated by antibiotic administration. ConclusionsOur findings highlight the potential impact of modifications in the intestinal microbiota on the severity of CDD symptoms, expanding our understanding beyond GI disturbances to encompass influences on neurological outcomes. This cross-border study provides valuable insights into the intricate interplay between gut microbiota and neurodevelopmental disorders.

neuroscience↗

bioRxiv2023

Gut microbiota profile in CDKL5 deficiency disorder patients as a potential marker of clinical severity

CDKL5 deficiency disorder (CDD) is a neurodevelopmental condition characterized by global developmental delay, early-onset seizures, intellectual disability, visual and motor impairments. Unlike Rett Syndrome (RTT), CDD lacks a clear regression period. CDD patients frequently encounter gastrointestinal (GI) disturbances and exhibit signs of subclinical immune dysregulation. However, the underlying causes of these conditions remain elusive. Emerging studies indicate a potential connection between neurological disorders and gut microbiota, an area completely unexplored in CDD. We conducted a pioneering study, analyzing fecal microbiota composition in CDD patients and their healthy relatives. Notably, differences in intestinal bacterial diversity and composition were identified in CDD patients. We further investigated microbiota changes based on the severity of GI issues, seizure frequency, sleep disorders, food intake type, impairment in neuro-behavioral features (assessed through the RTT Behaviour Questionnaire - RSBQ), and ambulation capacity. Our findings hint at a potential connection between CDD, microbiota, and symptom severity. This study marks the first exploration of the gut-microbiota-brain axis in CDD patients. It adds to the growing body of research emphasizing the role of the gut microbiota in neurodevelopmental disorders and opens doors to potential interventions that target intestinal microbes with the aim of improving the lives of CDD patients.

microbiology↗

bioRxiv2023

A Comprehensive Atlas of Perineuronal Net Distribution and Colocalization with Parvalbumin in the Adult Mouse Brain

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved in various forms of plasticity and clinical conditions. However, our understanding of the PNN role in these phenomena is limited by the lack of highly quantitative maps of PNN distribution and association with specific cell types. Here, we present the first comprehensive atlas of PNN distribution (in Allen Brain Atlas coordinates) and colocalization with parvalbumin (PV) cells for over 600 regions of the adult mouse brain. Data analysis showed that PV expression is a good predictor of PNN aggregation. In the cortex, PNNs are dramatically enriched in layer 4 of all primary sensory areas in correlation with thalamocortical input density, and their distribution mirrors intracortical connectivity patterns. Gene expression analysis identified many PNN correlated genes. Strikingly, PNN anticorrelated transcripts were enriched in synaptic plasticity genes, generalizing PNN role as circuit stability factors. Overall, this atlas offers novel resources for understanding the organizational principles of the brain extracellular matrix.

neuroscience↗

bioRxiv2021

The gut microbiota of environmentally enriched mice regulates visual cortical plasticity

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function and plasticity. The poorly known "EE derived signals" mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis of intestinal bacteria composition in EE mice revealed striking differences from standard condition (ST) animals and enhanced levels of short-chain fatty acids (SCFA). Depleting the EE mice gut microbiota with an antibiotic cocktail decreased SCFA and prevented EE induction of adult ocular dominance (OD) plasticity, spine dynamics and microglia rearrangement. SCFA treatment in ST mice mimicked the EE induction of adult OD plasticity and morphological microglial rearrangement. Remarkably, transferring the microbiota of EE mice to ST recipients activated adult OD plasticity. Thus, taken together our data suggest that experience-dependent changes in gut microbiota regulate brain plasticity.

neuroscience↗

bioRxiv2021

Brain histone beta-hydroxy-butyrylation couples metabolism with gene expression

Little is known about the impact of metabolic stimuli on brain tissue at a molecular level. The ketone body beta-hydroxybutyrate (BHB) can be a signaling molecule regulating gene transcription. Thus, we assessed lysine beta-hydroxybutyrylation (K-bhb) levels in proteins extracted from the cerebral cortex of mice undergoing a ketogenic metabolic challenge (48 hrs fasting). We found that fasting enhanced K-bhb in a variety of proteins including histone H3. ChIP-seq experiments showed that K9 beta-hydroxybutyrylation of H3 (H3K9-bhb) was significantly enriched by fasting on more than 8000 DNA loci. Transcriptomic analysis showed that H3K9-bhb on enhancers and promoters correlated with active gene expression. One of the most enriched functional annotations both at the epigenetic and transcriptional level was "circadian rhythms. Indeed, we found that the diurnal oscillation of specific transcripts was modulated by fasting at distinct zeitgebers both in the cortex and suprachiasmatic nucleus. Moreover, specific changes in locomotor activity daily features were observed during re-feeding after 48-hour fasting. Thus, our results suggest that fasting dramatically impinges on the cerebral cortex transcriptional and epigenetic landscape, and BHB acts as a powerful epigenetic molecule in the brain through direct and specific histone marks remodeling in neural tissue cells.

neuroscience↗