Biology subjects

Harsan, L.-A.

Publications and source records attributed to Harsan, L.-A..

3 recordsLinked to original sources

bioRxiv2025

Exploring sex-specific alterations in early Alzheimer's disease using network MRI analyses

Alzheimers disease (AD) is characterized by the accumulation of amyloid-{beta} plaques and tau neurofibrillary tangles, leading to progressive cognitive decline. Subtle cognitive and neural adaptations mark the preclinical stage of AD, occurring years before mild cognitive impairment and AD diagnosis. Throughout the continuum of AD, women ([~]60% of AD cases) demonstrate faster rates of cognitive decline, greater hippocampal atrophy, and more extensive tau pathology compared to men. This is particularly evident in early AD phases. Therefore, investigating early sex-specific changes is crucial for identifying biomarkers and developing targeted interventions. In the present study, we conducted a longitudinal investigation on the AppNL-F/MAPT double knock-in (dKI) mouse model, to identify sex-specific resting-state functional connectivity (FC) patterns associated with early cognitive deficits. Male and female wild-type and dKI mice were tested for associative and long-term memory deficits, followed by resting-state functional magnetic resonance imaging to examine the default mode network (DMN) connectivity at 2 and 4 months of age. Female dKI mice exhibited earlier and more pronounced memory impairments, with deficits apparent at 2 months, while male deficits emerged at 4 months. FC analyses revealed distinct sex-specific alterations within DMN and between DMN hubs and memory processing nodes. Notably, female dKI mice showed hypersynchrony between the retrosplenial cortex (RSP) and key memory-related regions such as the entorhinal cortex (ENT) and hippocampus (HIP), but also towards subcortical regions overlapping thalamic nuclei, amygdala, and substantia nigra. Meanwhile, male dKI mice exhibited hypoconnectivity along RSP-HIP axis, RSP-reuniens nucleus, and RSP-sensorimotor cortex. Our data particularly highlight sexually dimorphic RSP-ENT and RSP-HIP connectivity. These results underscore the critical role of sex in shaping neural network reorganization and cognitive decline during preclinical AD. These findings position neural network connectivity as a sensitive biomarker of early memory dysfunction and highlight the need for sex-specific investigations and potentially tailored therapeutic strategies in AD.

neuroscience↗

bioRxiv2019

Mapping the living mouse brain neural architecture: strain specific patterns of brain structural and functional connectivity

Mapping the structural and functional brain connectivity fingerprints became an essential approach in neurology and experimental neuroscience because network properties can underlie behavioral phenotypes. In mouse models, revealing strain related patterns of brain wiring have a tremendous importance, since these animals are used to answer questions related to neurological or neuropsychiatric disorders. C57BL/6 and BALB/cJ inbred strains are primary \"genetic backgrounds\" for brain disease modelling and for testing therapeutic approaches. Nevertheless, extensive literature describes basal differences in the behavioral, neuroanatomical and neurochemical profiles of the two strains, which raises the question whether the observed effects are pathology specific or depend on the genetic background. Here we performed a systematic comparative exploration of brain structure and function of C57BL/6 and BALB/cJ mice via Magnetic Resonance Imaging (MRI). We combined voxel-based morphometry (VBM), diffusion MRI and high resolution fiber mapping (hrFM) and resting state functional MRI (rs-fMRI) and depicted brain-wide dissimilarities in the morphology and \"connectome\" features in the two strains. Particularly C57BL/6 animals show bigger and denser frontal cortical areas, cortico-striatal tracts and thalamic and midbrain pathways, and higher density of fibers in the genu and splenium of the corpus callosum. These features are fairly reflected in the functional connectograms that emphasize differences in \"hubness\", frontal cortical and basal forbrain connectivity. We demonstrate strongly divergent reward-aversion circuitry patterns and some variations of the default mode network features. Inter-hemispherical functional connectivity showed flexibility and adjustment regarding the structural patterns in a strain specific manner. We further provide high-resolution tractograms illustrating also inter-individual variability across inter-hemispherical callosal pathways in the BALB/cJ strain.

neuroscience↗

bioRxiv2019

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

neuroscience↗