Progressive tremor and motor impairment in seizure-prone mutant tremor mice are associated with neurotransmitter dysfunction.

Autor: Gonçalves FB; Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP 04026-002, Brazil., Garcia-Gomes MSA; Department of Psychiatric, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada., Silva-Sampaio AC; Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP 04026-002, Brazil., Kirsten TB; Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP 04026-002, Brazil., Bondan EF; Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP 04026-002, Brazil., Sandini TM; Department of Psychiatric, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada., Flório JC; Program in Experimental and Comparative Pathology, Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo, SP 05508-270, Brazil., Lebrun I; Laboratory of Biochemistry and Biophysics, Program in Toxinology, Butantan Institute, Brazil., Coque AC; Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP 04026-002, Brazil., Alexandre-Ribeiro SR; Department of Immunology at the Institute of Biomedical Sciences/São Paulo University, Brazil., Massironi SMG; Program in Experimental and Comparative Pathology, Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo, SP 05508-270, Brazil., Mori CMC; Program in Experimental and Comparative Pathology, Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo, SP 05508-270, Brazil., Bernardi MM; Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, Rua Dr. Bacelar, 1212, São Paulo, SP 04026-002, Brazil. Electronic address: maria.bernardi@docente.unip.br.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2023 Apr 12; Vol. 443, pp. 114329. Date of Electronic Publication: 2023 Feb 04.
DOI: 10.1016/j.bbr.2023.114329
Abstrakt: Background: The tremor mutant mice present motor impairments comprised of whole-body tremors, ataxia, decreased exploratory behavior, and audiogenic seizures.
Objectives: This study aims to investigate the development of motor dysfunction in this mutant mouse and the relationships with cortical, striatal, and cerebellar levels of GABA, glutamate, glycine, dopamine (DA), serotonin (5-HT), noradrenaline (NOR), and its metabolites. The serum cytokines levels, myelin content, and the astrocytic expression of the glial fibrillary acidic protein (GFAP) investigated the possible influence of inflammation in motor dysfunction.
Results: Relative to wild-type (WT) mice, the tremor mice presented: increased tremors and bradykinesia associated with postural instability, decreased range of motion, and difficulty in initiating voluntary movements directly proportional to age; reduced step length for right and left hindlimbs; reduced cortical GABA, glutamate and, aspartate levels, the DOPAC/DA and ratio and increased the NOR levels; in the striatum, the levels of glycine and aspartate were reduced while the HVA levels, the HVA/DA and 5HIAA/5-HT ratios increased; in the cerebellum the glycine, NOR and 5-HIAA levels increased.
Conclusions: We suggest that the motor disturbances resulted mainly from the activation of the indirect striatal inhibitory pathway to the frontal cortex mediated by GABA, glutamate, and aspartate, reducing the dopaminergic activity at the prefrontal cortex, which was associated with the progressive tremor. The reduced striatal and increased cerebellar glycine levels could be partially responsible for the mutant tremor motor disturbances.
Competing Interests: Conflict of Interest Statement The authors declare no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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