The absence of the aryl hydrocarbon receptor in the R6/1 transgenic mouse model of Huntington's disease improves the neurological phenotype.

Autor: Angeles-López QD; Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, 07360, Mexico; Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, 14269, Mexico., García-Lara L; Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, 14269, Mexico., Aguirre-Pineda N; Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, 07360, Mexico., Castañeda-Arellano R; Departamento de Ciencias Biomédicas, Centro Universitario de Tonalá, Universidad de Guadalajara 45425, Jalisco, Mexico., Elizondo-Azuela G; Departamento de Biología Celular, Centro de Investigación y de Estudios Avanzados del IPN, 07360, Mexico., Pérez-Severiano F; Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, 14269, Mexico., Segovia J; Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, 07360, Mexico. Electronic address: jsegovia@fisio.cinvestav.mx.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2021 Jun 25; Vol. 408, pp. 113230. Date of Electronic Publication: 2021 Mar 05.
DOI: 10.1016/j.bbr.2021.113230
Abstrakt: Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an abnormal CAG repeat expansion in the huntingtin gene coding for a protein with an elongated polyglutamine sequence. HD patients present choreiform movements, which are caused by the loss of neurons in the striatum and cerebral cortex. Previous reports indicate that the absence of the aryl hydrocarbon receptor (AhR) protects mice from excitotoxic insults and increases the transcription of neurotrophic factors. Based on these data, we evaluated the effects of the lack of the AhR on a mice model of HD, generating a double transgenic mouse, expressing human mutated huntingtin (R6/1 mice) and knockout for the AhR. Our results show that the body weight of 30-week-old double transgenic mice is similar to that of R6/1 mice; however, feet clasping, an indicative of neuronal damage in the R6/1 animals, was not observed. In addition, motor coordination and ambulatory behavior in double transgenic mice did not deteriorate over time as occur in the R6/1 mice. Moreover, the anxiety behavior of double transgenic mice was similar to wild type mice. Interestingly, astrogliosis is also reduced in the double transgenic mice. The present data demonstrate that the complete loss of the AhR reduces the motor and behavioral deterioration observed in R6/1 mice, suggesting that the pharmacological modulation of the AhR could be a therapeutic target in HD.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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