Central alteration in peripheral neuropathy of Trembler-J mice: hippocampal pmp22 expression and behavioral profile in anxiety tests

Damián, Juan Pablo - Vázquez Alberdi, Lucía - Canclini, Lucía - Rosso, Gonzalo - Olivera Bravo, Silvia - Martínez Barreiro, Mariana - Uriarte, Natalia - Ruiz, Paul - Calero, Miguel - Di Tomaso, María Vittoria - Kun González, Alejandra E.

Resumen:

Charcot–Marie–Tooth (CMT) type 1 disease is the most common human hereditary demyelinating neuropathy. Mutations in pmp22 cause about 70% of all CMT1. Trembler-J (TrJ/+) mice are an animal model of CMT1E, having the same spontaneous pmp22 mutation that is found in humans. We compared the behavior profile of TrJ/+ and +/+ (wild-type) in open-field and elevated-plus-maze anxiety tests. In these tests, TrJ/+ showed an exclusive head shake movement, a lower frequency of rearing, but a greater frequency of grooming. In elevated-plus-maze, TrJ/+ defecate more frequently, performed fewer total entries, and have fewer entries to closed arms. These hippocampus-associated behaviors in TrJ/+ are consistent with increased anxiety levels. The expression of pmp22 and soluble PMP22 were evaluated in E17-hippocampal neurons and adult hippocampus by in situ hybridization and successive immunohistochemistry. Likewise, the expression of pmp22 was confirmed by RT-qPCR in the entire isolated hippocampi of both genotypes. Moreover, the presence of aggregated PMP22 was evidenced in unmasked granular hippocampal adult neurons and shows genotypic differences. We showed for the first time a behavior profile trait associated with anxiety and a differential expression of pmp22/PMP22 in hippocampal neurons of TrJ/+ and +/+ mice, demonstrating the involvement at the central level in an animal model of peripheral neuropathy (CMT1E).


Detalles Bibliográficos
2021
ANII: FCE_1_2019_155539
Charcot–Marie–Tooth
Hippocampus
Peripheral-myelin-protein-22
Anxiety
Trembler-J
CA3 neurons
Inglés
Universidad de la República
COLIBRI
https://hdl.handle.net/20.500.12008/38314
Acceso abierto
Licencia Creative Commons Atribución (CC - By 4.0)