Biology subjects

Boda, E.

Publications and source records attributed to Boda, E..

5 recordsLinked to original sources

bioRxiv2026

Oligodendroglial deletion of the microcephaly gene Cit-k disrupts cortical connectivity and cognitive function

Neurodevelopmental disorders (NDDs) are increasingly recognized as disorders of brain connectivity and circuit dysfunction. Growing evidence suggests that glial cell and myelin abnormalities may actively contribute to these alterations. Yet, they have been often considered secondary consequences of impaired neuronal development rather than primary drivers of circuit dysfunction. Primary autosomal recessive microcephaly type 17 (MCPH17) is a severe NDD caused by mutations in the CIT gene, encoding Citron kinase (CIT-K). The disease is associated with cognitive and motor deficits, epilepsy susceptibility, and marked hypomyelination in both patients and mouse models, suggesting a contribution of oligodendroglial dysfunction to disease pathophysiology. Here, we investigated the specific role of oligodendroglial Cit-k loss using Sox10Cre;Cit-kfl/fl mice, in which Cit-k is selectively deleted in oligodendrocyte-lineage cells. Mutant mice displayed impaired forebrain myelination at juvenile stages and persistent cortical hypomyelination in adulthood. Despite preserved gross motor function, adult mutants showed deficits in fine motor control, working and recognition memory, and auditory fear memory. These impairments were associated with altered cortico-cortical and cortico-hippocampal functional connectivity. Moreover, consistent with the clinical MCPH17 phenotype, mutant mice exhibited increased susceptibility to kainate-induced seizures. Together, our findings show that oligodendroglial Cit-k loss and the resulting hypomyelination are sufficient to produce long-lasting neurological and behavioral impairments independently of primary neuronal defects. These results identify oligodendrocytes as active contributors to MCPH17 and support a broader role for myelin abnormalities in NDDs. HighlightsO_LICit-k deletion in oligodendroglia disrupts forebrain myelination C_LIO_LICortical hypomyelination persists in adult mutant mice C_LIO_LIMutant mice show deficits in motor control and memory C_LIO_LICortico-cortical and cortico-hippocampal connectivity are altered C_LIO_LIligodendrocytes contribute to microcephaly-associated dysfunctions C_LI

neuroscience↗

bioRxiv2026

Transcranial direct current stimulation (tDCS) promotes myelin repair and plasticity in the mouse motor cortex

Cortical myelin loss and oligodendroglial dysfunction, hallmarks of numerous neurodegenerative and psychiatric disorders, compromise executive, sensory, and cognitive functions by altering circuit activity and integrity. Promoting cortical myelin repair therefore represents a critical therapeutic goal. In this frame, modulation of neuronal activity through non-invasive brain stimulation may represent a promising non-pharmacological approach to support remyelination. To address this issue, we investigated the effects of anodal transcranial direct current stimulation (A-tDCS) in a mouse model of unilateral myelin injury in the motor cortex. A-tDCS was delivered over the contralateral uninjured cortex during a bilateral motor task (locomotion), to enhance the physiological activity of interhemispheric M1-M1 projections and indirectly stimulate the lesioned cortex. When applied during the late phase of demyelination and the onset of repair, A-tDCS accelerated remyelination and increased oligodendroglial survival and maturation in the lesioned cortex, compared with unstimulated controls. Increased myelin was also detected in the directly stimulated uninjured cortex despite unchanged oligodendroglial cell numbers, suggesting de novo myelin formation or remodeling of existing internodes. These structural changes were accompanied by preservation of interhemispheric M1-M1 functional connectivity upon injury. Collectively, our findings demonstrate that A-tDCS promotes cortical myelin repair in vivo, supporting its therapeutic potential for disorders characterized by myelin damage. Notably, the observed effects of tDCS on myelin plasticity in the uninjured cortex - reported here for the first time - reveal a previously unrecognized mechanism underlying tDCS-mediated neuromodulation. HighlightsO_LIAnodal tDCS (A-tDCS) promotes remyelination in the mouse motor cortex (M1) and restores M1-M1 synchrony after demyelinating injury C_LIO_LIA-tDCS enhances oligodendroglial survival and maturation in the injured motor cortex C_LIO_LIA-tDCS induces myelin plasticity in the uninjured cortex C_LI

neuroscience↗

bioRxiv2025

A single-cell transcriptomic atlas maps cerebellar astrocyte diversity and uncovers the transcriptional code underlying their maturation trajectories

Astrocytes are increasingly recognized as key regulators of neural circuit development and function, with mounting evidence revealing substantial heterogeneity within and across brain regions. Yet, the full extent of this diversity and its developmental mechanisms remain poorly understood. To address this, we leveraged the uniqueness of the mouse cerebellum, which hosts well-defined astrocyte types and established progenitor pools. Through complementary multi-modal omic approaches, including single-cell RNA sequencing, spatial transcriptomics, trajectory inference, clonal lineage reconstruction, and gene expression and regulatory network analyses, we systematically dissected the molecular diversity and ontogenesis of cerebellar astrocytes. We identified known types and uncovered new subtypes with functional specialization, inferring their developmental trajectories from multiple embryonic niches and postnatal progenitor sources with fate divergence, convergence, and restriction. We further predicted a hierarchical transcriptional regulator code governing this diversification, operating at multiple levels: distinct regulatory modules i) reflect embryonic regionalization and lineage; ii) determine broad astroglial identity; specify iii) Bergmann versus non-Bergmann fates; and guide iv) astrocyte type and v) subtype acquisition. Our findings map and temporally organize transcriptional programs that capture key determinants of astrocyte fate, integrating them along defined trajectories toward diverse astrocyte identities. This high-resolution framework for cerebellar glial diversification offers a model to be challenged across other brain regions.

neuroscience↗

bioRxiv2025

Acute particulate matter (PM10) exposure selectively triggers behavioral alterations in the presymptomatic Experimental Autoimmune Encephalomyelitis (EAE) mouse model of Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic disease of the Central Nervous System, where neuroinflammation and autoimmune response against myelin lead to functional impairments, cognitive and psychiatric symptoms. Exposure to air pollution - in particular to peaks of particulate matter (PM) - has been associated with an increase of hospital admissions for MS onset and relapses and exacerbated neuroinflammation in MS patients. Here, in the MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) mouse model of MS, we tested the hypothesis that exposure to PM10 might influence the disease course and severity in individuals with a predisposing background. Short-term PM10 exposures - occurring either before immunization or during the pre-symptomatic phase - did not modify disease manifestation in EAE mice, as assessed by clinical and neuropathological analyses. Yet, presymptomatic EAE - but not healthy - mice selectively showed increased disinhibited, risk-taking and novelty-seeking behaviors early after being exposed to PM10. These data show a selective vulnerability of immunologically primed mice toward the effects of PM10, occurring before the emergence of overt motor impairment and presenting as specific behavioral alterations.

neuroscience↗

bioRxiv2023

Mecp2 knock-out astrocytes affect synaptogenesis by IL-6 dependent mechanisms

Synaptic abnormalities represent a hallmark for several neurological diseases and clarification of the underlying mechanisms constitutes a crucial step towards the development of therapeutic strategies. Rett syndrome (RTT) is a rare neurodevelopmental disorder, mainly affecting females, caused by heterozygous mutations in the X-linked Methyl-CpG-Binding Protein 2 (MECP2) gene, leading to a deep derangement of synaptic connectivity. Although initial studies have supported the exclusive involvement of neurons, recent data have highlighted the pivotal contribution of astrocytes in RTT pathogenesis through non-cell autonomous mechanisms. Since astrocytes regulate synaptogenesis by releasing multiple molecules, we investigated the influence of soluble factors secreted by Mecp2 KO astrocytes on synaptic density. We found that Mecp2 deficiency in astrocytes negatively affects their ability to support synapse formation by releasing synaptotoxic molecules, among which we identified interleukin-6 (IL-6). Notably, aberrant IL-6 expression exclusively emerges from a dysfunctional astrocyte-neuron crosstalk, and blocking IL-6 activity prevents synaptic alterations.

neuroscience↗