Female Rats Are Resistant to Cognitive, Motor and Dopaminergic Deficits in the Reserpine-Induced Progressive Model of Parkinson's Disease.

Autor:	Lima AC; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Meurer YSR; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil.; Memory and Cognition Studies Laboratory, Department of Psychology, Universidade Federal da Paraíba, João Pessoa, Brazil., Bioni VS; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Cunha DMG; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Gonçalves N; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Lopes-Silva LB; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Becegato M; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Soares MBL; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Marinho GF; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil., Santos JR; Behavioral and Evolutionary Neurobiology Laboratory, Department of Biosciences, Universidade Federal de Sergipe, Itabaiana, Brazil., Silva RH; Behavioral Neuroscience Laboratory, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in aging neuroscience [Front Aging Neurosci] 2021 Oct 25; Vol. 13, pp. 757714. Date of Electronic Publication: 2021 Oct 25 (Print Publication: 2021).
DOI:	10.3389/fnagi.2021.757714
Abstrakt:	Parkinson's disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10-15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Lima, Meurer, Bioni, Cunha, Gonçalves, Lopes-Silva, Becegato, Soares, Marinho, Santos and Silva.)
Databáze:	MEDLINE
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