Functional ultrasound and brain connectivity reveal central nervous system compromise in Trembler-J mice model of Charcot-Marie-Tooth disease

Anzibar Fialho, Maximiliano - Martínez Barreiro, Mariana - Vázquez Alberdi, Lucía - Damián Cabrera, Juan Pablo - Di Tomaso, María Vittoria - Baranger, Jerome - Tanter, Mickael - Calero, Miguel - Negreira, Carlos - Rubido, Nicolás - Kun González, Alejandra E. - Brum, Javier

Resumen:

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.

Detalles Bibliográficos
2024
ANII: FCE_1_2019_1_155539
ANII: POS_NAC_M_2020_1_164127
ANII: POS_FCE_2020_1_1009181
ANII: POS_NAC_2022_1_173578
CSIC: 2018-FID 13-Grupo ID 722.
CSIC: I+D 497725-2023-2027
Biological physics
Diseases of the nervous system
Imaging techniques
Neuro–vascular interactions
Neuroscience
Peripheral nervous system
Physiology
Somatosensory system
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/48667
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)