Sex differences in the progressive model of parkinsonism induced by reserpine in rats

Bispo, José M.M.; Melo, João E C; Gois, Auderlan M.; Leal, Pollyana Caldeira; Lins, Lucas Correia; Souza, Marina F.; Medeiros, Katty A.A.L.; Ribeiro, Alessandra Mussi; Silva, Regina H.; Marchioro, Murilo; Santos, José R.

doi:10.1016/j.bbr.2019.01.041

Cited by 21 publications

(14 citation statements)

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“…Nevertheless, Restreated rats, irrespective of sex, presented a significant decrease in motor activity 48 h after the 10th and 15th injections. In this regard, other studies have described similar effects for males (Santos et al, 2013;Leão et al, 2017;Lins et al, 2018;Bispo et al, 2019) and females (Bispo et al, 2019). Although there is a visually more pronounced reduction in locomotion in reserpine females than in males in the second open field session, statistical analysis did not show a significant interaction between time (repeated sessions) and sex.…”

Section: Discussionsupporting

confidence: 64%

“…In this work, we investigated sex differences in motor, cognitive and neurochemical alterations at different stages of repeated low-dose reserpine administration, a progressive animal model of PD ( Santos et al, 2013 ; Leão et al, 2015 , 2017 ; Peres et al, 2016 ; Campelo et al, 2017 ; Lins et al, 2018 ; Bispo et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, whether or not estradiol protects the dopaminergic pathways in experimental PD appears to vary according some experimental conditions (e.g., neurotoxin used, the severity of the lesion, the strain and species of rodent and the treatment regimen) as well as sex (McArthur et al, 2007). For example, in a previous study Bispo et al (2019) have shown that ovariectomized females have decreased catalepsy compared to intact male and female rats, although showing a loss in TH + cells in SNpc.…”

Section: Introductionmentioning

confidence: 99%

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

Lima

Meurer

Bioni

et al. 2021

Front. Aging Neurosci.

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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.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lima

Meurer

Bioni

et al. 2021

Front. Aging Neurosci.

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“…Female dopaminergic cells generally show lesser vulnerability to factors inducing degeneration than male neurons. Accordingly, reserpine-treated female rats did not show any reduction of tyrosine hydroxylase immunoreactivity in the SNc and dorsal striatum compared to males [90]. The lack of Ras homolog enriched in striatum (Rhes), a protein that exert pleiotropic effects on cell function, in KO mice induced a decrease in tyrosine hydroxylase expression in males only, while KO females showed resistance to DA neuron degeneration, which tended to decrease only with aging [91,92].…”

Section: Dopaminergic Neurodegenerationmentioning

confidence: 88%

Parkinson’s Disease in Women and Men: What’s the Difference?

Cerri¹,

Mus²,

Blandini³

2019

Journal of Parkinson’s Disease

484

309

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Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.

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“…Motor deficits are associated with the dopaminergic reduction in PD 19,58 . Repeated administrations of RES decrease the density of fibres in the STR and the number of TH + neurons in the SNpc 59 . In addition, RES‐treatment also increases striatal lipid peroxidation 42 .…”

Section: Discussionmentioning

confidence: 99%

Myrtenol complexed with β‐cyclodextrin ameliorates behavioural deficits and reduces oxidative stress in the reserpine‐induced animal model of Parkinsonism

Silva-Martins

Beserra-Filho

Maria-Macêdo

et al. 2021

Clin Exp Pharma Physio

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Current pharmacological approaches to treat Parkinson’s disease have low long‐term efficacy and important adverse side effects. The development of new pharmacological therapies has focused on novel plant‐derived phytochemicals. The alcoholic monoterpene myrtenol has been isolated from several plant species, and has anxiolytic, analgesic, anti‐inflammatory and antioxidant actions. Our study evaluated the neuroprotective potential of myrtenol complexed with β‐cyclodextrin (MYR) on a progressive parkinsonism model induced by reserpine (RES) in mice. The complexation with cyclodextrins enhances the pharmacological action of monoterpenes. Male Swiss mice were treated daily with MYR (5 mg/kg, p.o.) and with RES (0.1 mg/kg, s.c.) every other day during 28 days. Behavioural evaluations were conducted across treatment. At the end of the treatment, immunohistochemistry for tyrosine hydroxylase (TH) and oxidative stress parameters were evaluated. Chronic MYR‐treatment protected against olfactory sensibility loss, restored short‐term memory and decreased RES‐induced motor impairments. Moreover, this treatment prevented dopaminergic depletion and reduced the oxidative status index in the dorsal striatum. Therefore, MYR ameliorated motor and non‐motor impairments in the progressive animal model of parkinsonism, possibly by an antioxidant action. Additional research is needed to investigate the mechanisms involved in this neuroprotective effect.

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Sex differences in the progressive model of parkinsonism induced by reserpine in rats

Cited by 21 publications

References 50 publications

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

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

Parkinson’s Disease in Women and Men: What’s the Difference?

Myrtenol complexed with β‐cyclodextrin ameliorates behavioural deficits and reduces oxidative stress in the reserpine‐induced animal model of Parkinsonism

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