Functional ultrasound and brain connectivity reveal central nervous system compromise in Trembler-J mice model of Charcot-Marie-Tooth disease
The Charcot-Marie-Tooth-1E (CMT1E) disease is typically described as a peripheral neuropathy in humans, causing decreased nerve conduction, spastic paralysis, and tremor. The Trembler-J (TrJ) mice serve as a high fidelity model of this disease. Here, we use functional ultrasound (fUS) and functional connectivity (FC) to analyze TrJ mice's brain activity during sensory stimulation and resting state experiments against wild type (WT) mice - the healthy counterpart. fUS is an imaging technique that measures cerebral blood volume (CBV) temporal changes. We study these changes in the primary somatosensory cortex barrel field (S1BF) of both mice populations during periodic vibrissae stimulation, measuring the number of pixels that correlate to the stimulation (i.e., the size of the activation area), the average correlation of these pixels (i.e., the response strength), and the CBV's rate of change for each stimulation (i.e., the hemodynamic response). Then, we construct a FC matrix for each genotype and experiment by correlating the CBV signals from the eight cortical regions defined by the Paxinos and Franklin atlas. Our results show that TrJ mice have significantly diminished neurovascular responses and altered brain connectivity with respect to WT mice, pointing to central nervous system effects that could shift our understanding of the CMT1E disease.
Authors
- Nicolás Rubido (ORCID: https://orcid.org/0000-0002-0616-2479)
- Maximiliano Anzibar Fialho (ORCID: https://orcid.org/0000-0001-8075-5195)
- María Vittoria Di Tomaso (ORCID: https://orcid.org/0000-0001-8026-584X)
- Miguel Calero (ORCID: https://orcid.org/0000-0001-5366-3324)
- Alejandra Kun (ORCID: https://orcid.org/0000-0002-7070-0171)
- Jérôme Baranger (ORCID: https://orcid.org/0000-0002-2311-716X)
- Javier Brum (ORCID: https://orcid.org/0000-0002-3429-126X)
- Lucía Vázquez Alberdi (ORCID: https://orcid.org/0000-0002-3398-4961)
- Carlos Negreira (ORCID: https://orcid.org/0000-0002-2640-9352)
- Juan Pablo Damián (ORCID: https://orcid.org/0000-0001-8042-5743)
- Mariana Martínez Barreiro
- Mickaël Tanter (ORCID: https://orcid.org/0000-0001-7739-8051)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Universidad de la República de Uruguay (UY)
- University of Aberdeen (GB)
- Université Paris Sciences et Lettres (FR)
- Instituto de Salud Carlos III (ES)
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Unidad Funcional de Investigación de Enfermedades Crónicas (ES)
- Instituto de Investigaciones Biológicas Clemente Estable (UY)
- Physique pour la médecine Paris (FR)
- Universidad de Montevideo (UY)
- ESPCI Paris (FR)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-12-03
- DOI
- https://doi.org/10.1038/s41598-024-80022-z
- Citations
- 1
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.27
Funders
- Agencia Nacional de Investigación e Innovación
- Centre National de la Recherche Scientifique
- Universidad de la República Uruguay
- Comisión Sectorial de Investigación Científica