Large-scale EM data reveals myelinated axonal changes and altered connectivity in the corpus callosum of an autism mouse model

Frontiers in Neuroinformatics, Journal Year: 2025, Volume and Issue: 19

Published: April 11, 2025

Introduction Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders with complex etiologies, including genetic, environmental, and neuroanatomical factors. While the exact mechanisms underlying ASD remain unclear, structural abnormalities in brain offer valuable insights into its pathophysiology. The corpus callosum, largest white matter tract brain, plays crucial role interhemispheric communication, may contribute to ASD-related phenotypes. Methods To investigate ultrastructural alterations callosum associated ASD, we utilized serial scanning electron microscopy (sSEM) mice. A dataset entire sagittal sections from wild-type Shank3B mutant mice was acquired at 4 nm resolution, enabling precise comparisons myelinated axon properties. Leveraging fine-tuned EM-SAM model for automated segmentation, quantitatively analyzed key metrics, G-ratio, myelin thickness, axonal density. Results In autism mouse, observed significant increase density, accompanied by thinner sheaths compared wild-type. Additionally, identified diameter distribution axons deviations G-ratio. Notably, these were widespread across suggesting global disruption integrity. Discussion This study provides novel microstructural supporting hypothesis that myelination deficits communication impairments between hemispheres. However, given focus this study, further research integrating functional assessments is necessary establish direct link morphological changes neural dysfunction.

Language: Английский

Age-dependent cortical overconnectivity in Shank3 mice is reversed by anesthesia

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 19, 2025

Growing evidence points to brain network dysfunction as a central neurobiological basis for autism spectrum disorders (ASDs). As result, studies on Functional Connectivity (FC) have become pivotal understanding the large-scale alterations associated with ASD. Despite ASD being neurodevelopmental disorder, and FC significantly influenced by state, existing in mouse models predominantly focus adult subjects under anesthesia. The differential impact of anesthesia age cortical functional networks remains unexplored. To fill this gap, we conducted longitudinal evaluation across three states ages Shank3b model autism. We utilized wide-field calcium imaging monitor activity Shank3b+/- Shank3b+/+ mice from late development (P45) through adulthood (P90), isoflurane manipulate state. Our findings reveal that hyperconnectivity, emerging barrel-field cortices during juvenile stage, progressively expands encompass entire dorsal cortex mice. Notably, severity imbalance is highly dependent state: global are more pronounced awake state strongly reduced These results underscore crucial role detecting autism-related identify significant early This represents potential target non-invasive translational treatments.

Language: Английский

Age-dependent cortical overconnectivity revers under anesthesia in Shank3 mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

Growing evidence points to brain network dysfunction as a central neurobiological basis for autism spectrum disorders (ASDs). As result, studies on Functional Connectivity (FC) have become pivotal understanding the large-scale alterations associated with ASD. Despite ASD being neurodevelopmental disorder, and FC significantly influenced by state, existing in mouse models predominantly focus adult subjects under anesthesia. The differential impact of anesthesia age cortical functional networks remains unexplored. To fill this gap, we conducted longitudinal evaluation across three states ages Shank3b model autism. We utilized wide-field calcium imaging monitor activity Shank3b+/- Shank3b+/+ mice from late development (P45) through adulthood (P90), isoflurane manipulate state. Our findings reveal that hyperconnectivity, emerging barrel-field cortices during juvenile stage, progressively expands encompass entire dorsal cortex mice. Notably, severity imbalance is highly dependent state: are more pronounced awake state shift towards hypoconnectivity These results underscore crucial role detecting autism-related identify significant early This represents potential target non-invasive translational treatments.

Language: Английский