Martinez-Tazo, P. | bioRxiv Science

bioRxiv2026

Longitudinal MRI reveals hormone-dependent brain remodeling supporting preserved cognition in aged females

Adaptive plasticity, the brains capacity to counteract structural decline and preserve performance with age, is a hallmark of successful aging, yet its biological underpinnings remain poorly understood. Here, we combined longitudinal magnetic resonance imaging (MRI) spanning the entire lifespan with electrophysiology, immunohistochemistry, and behavioral assays in female and male rats to identify key region- and systems-level mechanisms underlying this process. Resting-state functional MRI revealed a striking sex-specific pattern of connectivity reorganization in anterior brain regions, emerging in midlife and more pronounced in females. Microstructural MRI and histological analyses linked increased connectivity to prolonged white matter preservation and downstream maintenance of neuronal function in the female prefrontal cortex, while electrophysiological recordings demonstrated enhanced effective connectivity in the same region in aged females. Behaviorally, enhanced anterior connectivity was associated with superior memory performance. Ovariectomy at a critical time point for white matter maturation compromised this female-specific neuroprotection, disrupting microstructural integrity and functional reorganization, thereby highlighting the role of sex hormones in shaping these trajectories. Together, these findings identify a novel sexually dimorphic pattern of functional reorganization in anterior brain regions and point to estrogen availability during critical periods as a key modulator of brain aging.

neuroscience↗

bioRxiv2023

Sex matters: the MouseX DW-ALLEN Atlas for mice diffusion-weighted MR imaging

Overcoming sex bias in preclinical research requires not only including animals of both sexes in the experiments, but also developing proper tools to handle such data. Recent work revealed sensitivity of diffusion-weighted MRI to glia morphological changes in response to inflammatory stimuli, opening up exciting possibilities to characterize inflammation in a variety of preclinical models of pathologies, the great majority of them available in mice. However, there are limited resources dedicated to mouse imaging, like those required for the data processing and analysis. To fill this gap, we build a mouse MRI template of both structural and diffusion contrasts, with anatomical annotation according to the Allen Mouse Brain Atlas, the most detailed public resource for mouse brain investigation. To achieve a standardized resource, we use a large cohort of animals in vivo, and include animals of both sexes. To prove the utility of this resource to integrate imaging and molecular data, we demonstrate significant association between the mean diffusivity from MRI and gene expression-based glial counting. To demonstrate the need of equitable sex representation, we compared across sexes the warp fields needed to match a male-based template, and our template built with both sexes. Then, we use both templates for analysing mice imaging data obtained in animals of different ages, demonstrating that using a male-based template creates spurious significant sex effects, not present otherwise. All in all, our MouseX DW-ALLEN Atlas will be a widely useful resource getting us one step closer to equitable healthcare. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/568800v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@b3a616org.highwire.dtl.DTLVardef@5d2b3corg.highwire.dtl.DTLVardef@c1767borg.highwire.dtl.DTLVardef@149a259_HPS_FORMAT_FIGEXP M_FIG C_FIG

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