Sharlen Moore, Swati Subramanian, Martin Meschkat, Jonas W. Hemesath, Torben Ruhwedel, Wiebke Möbius, Klaus-Armin Nave, Livia de Hoz
{"title":"Early Myelination Supports the Establishment of Consistent Handedness","authors":"Sharlen Moore, Swati Subramanian, Martin Meschkat, Jonas W. Hemesath, Torben Ruhwedel, Wiebke Möbius, Klaus-Armin Nave, Livia de Hoz","doi":"10.1002/glia.70161","DOIUrl":"10.1002/glia.70161","url":null,"abstract":"<p>Lateralization of brain functions, such as handedness, is thought to enhance cortical efficacy by reducing redundancy and speeding up decision-making. The corpus callosum (CC), one of the brain's largest myelinated tracts, is critical for interhemispheric connectivity and has been implicated in lateralization. However, it is unclear whether the myelination of transcallosal axons contributes causally to lateralized functions. Here, we assessed the impact of myelin integrity in the circuits that regulate paw laterality in mice. We hypothesized that myelin, an essential component of CC architecture and required for rapid axonal impulse conduction, is necessary for the establishment and maintenance of handedness. To test this, we behaviorally assessed paw preference by differentially controlling the degree, localization, and timing of hypomyelination in different mouse models. As expected, control mice were strongly lateralized and showed an equal distribution of paw preference directionality (right or left). In contrast, dysmyelinated (<i>Mbp</i><sup><i>shi/shi</i></sup>) mice, which mastered the task without obvious impairments, exhibited reduced lateralization scores and were either ambidextrous or left-pawed. Interestingly, neither congenital myelination reduction (<i>Mbp</i><sup><i>neo/neo</i></sup>) nor forebrain-specific disruption of developmental myelination had an effect on paw lateralization. Similarly, demyelination induced in adulthood had no impact on paw preference. We conclude that the presence of compact myelin during early brain development is essential for the establishment of handedness, in a manner that is likely independent of fine axonal conduction velocity control. We propose a model in which developmental myelination is timed to support the establishment of key functional aspects of brain function, such as lateralization.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mickaël Pereira, Benjamin Vidal, Marco Valdebenito, Fatima Cheataini, Caroline Bouillot, Louis Vidal, Liam Nestor, Dimitri De Bundel, Ilse Smolders, Marine Droguerre, Luc Zimmer
{"title":"Dissociation Between Hemodynamic and Metabolic Responses to Chemogenetic Modulation of Astrocytes in Mouse Visual Cortex","authors":"Mickaël Pereira, Benjamin Vidal, Marco Valdebenito, Fatima Cheataini, Caroline Bouillot, Louis Vidal, Liam Nestor, Dimitri De Bundel, Ilse Smolders, Marine Droguerre, Luc Zimmer","doi":"10.1002/glia.70171","DOIUrl":"10.1002/glia.70171","url":null,"abstract":"<p>Astrocytes play a critical role in brain homeostasis and energetics, yet their exact contribution to neurovascular and neurometabolic coupling is not fully elucidated. In particular, how astrocytic activity participates in shaping the functional neuroimaging signals relying on these processes remains unclear. In this study, we used chemogenetic modulation of astrocytes in the primary visual cortex, by activation of Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs), to investigate their influence on spontaneous or sensory-driven hemodynamic fluctuations using functional ultrasound imaging (fUSi), as well as glucose uptake using [<sup>18</sup>F]FDG-positron emission tomography (PET). We found that astrocytic Gq-DREADD activation using clozapine-N-oxide (CNO) locally increased the amplitude of functional hyperemia during visual stimulation and vasomotion during resting-state. [<sup>18</sup>F]FDG signal was not significantly impacted, but changes in radiotracer uptake negatively correlated to changes in functional hyperemia across DREADDs-expressing mice. Our findings confirm that astrocytes are important players of sensory-driven as well as spontaneous cerebral hemodynamics, and nuance the view that astrocytic activity is the primary contributor of [<sup>18</sup>F]FDG PET. Moreover, they highlight astrocytes as a source of discrepancy between neurovascular and neurometabolic signals, both classically interpreted in terms of neuronal activity.</p>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/glia.70171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guanyu Li, Hong Liu, Zhida Lan, Yimin Yuan, Jiali Li, Ziwei Dai, Chao Huang, Cheng He, Shangyao Qin, Zhida Su
{"title":"Harnessing Microglial Repopulation: From Inflammatory Drivers to Therapeutic Allies in CNS Diseases","authors":"Guanyu Li, Hong Liu, Zhida Lan, Yimin Yuan, Jiali Li, Ziwei Dai, Chao Huang, Cheng He, Shangyao Qin, Zhida Su","doi":"10.1002/glia.70169","DOIUrl":"10.1002/glia.70169","url":null,"abstract":"<div>\u0000 \u0000 <p>Microglia, the tissue-resident macrophages of the central nervous system (CNS), execute essential functions in neural development, homeostasis, and repair. However, their persistent or dysregulated activation is a hallmark of diverse neurological disorders, where they transition from protective sentinels to drivers of chronic neuroinflammation and tissue damage. This duality has spurred the development of therapeutic strategies aimed not merely at suppressing microglial activity, but at fundamentally resetting the CNS immune landscape. Here, we review the paradigm of transient microglial depletion followed by endogenous repopulation, a strategy that effectively replaces a dysfunctional or pathologically primed microglial compartment with a rejuvenated cohort. Emerging evidence demonstrates that repopulated microglia exhibit a distinct phenotype—characterized by attenuated inflammatory profiles, upregulated homeostatic and neurotrophic gene expression, and enhanced phagocytic capacity—thereby conferring neuroprotection and promoting functional recovery across preclinical models of acute injury, neurodegeneration, and demyelinating disease. We critically evaluate the pharmacological and genetic tools used to achieve depletion, synthesize the context-dependent outcomes across disease spectra, and discuss the mechanistic basis for the superior therapeutic profile of the repopulation phase. Finally, we address the key translational challenges—including therapeutic windows, age- and sex-dependent effects, and the gap between rodent models and human biology—that must be overcome to transform this innovative strategy from a powerful experimental tool into a viable clinical modality for reprogramming CNS immunity.</p>\u0000 </div>","PeriodicalId":174,"journal":{"name":"Glia","volume":"74 7","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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