Alpha-Tocopherol Counteracts Cognitive and Motor Deficits Induced by Repeated Treatment with Reserpine

Sarmento-Silva, Aldair J.; Lima, Ramón Hypolito; Cabral, Alícia; Meurer, Ywlliane da Silva Rodrigues; Aless,; Ribeiro, Alessandra Mussi; Silva, Regina H.

doi:10.4172/2167-0501.1000153

Cited by 10 publications

(5 citation statements)

References 61 publications

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“…For this reason, treatment with antioxidants is able to revert reserpine‐induced oxidative stress and oral dyskinesia . Finally, the treatment with 40 mg/kg vitamin E concomitant to the repeated treatment with 0.1 mg/kg reserpine prevented cognitive and motor impairments , as well as the reduction of TH immunostaining in rats (unpublished data).…”

Section: Pharmacological and Predictive Quality Of The Reserpine Modelmentioning

confidence: 86%

Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long‐Standing Model

et al. 2015

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The administration of reserpine to rodents was one of the first models used to investigate the pathophysiology and screening for potential treatments of Parkinson's disease (PD). The reserpine model was critical to the understanding of the role of monoamine system in the regulation of motor and affective disorders, as well as the efficacy of current PD treatments, such as L-DOPA and dopamine agonists. Nevertheless, with the introduction of toxin-induced and genetic models of PD, reserpine became underused. The main rationale to this drawback was the supposed absence of reserpine construct validity with PD. Here, we highlight classical and recent experimental findings that support the face, pharmacological, and construct validity of reserpine PD model and reason against the current rationale for its underuse. We also aim to shed a new perspective upon the model by discussing the main challenges and potentials for the reserpine model of PD.

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Section: Pharmacological and Predictive Quality Of The Reserpine Modelmentioning

confidence: 86%

Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long‐Standing Model

et al. 2015

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“…Consistent with our data, Guimaraes et al (2015) showed that α-Tocopherol could modulate memory formation and preserve cognition in the Stork model ( Guimaraes et al, 2015 ). Sarmento-Silva et al (2014) conducted the antioxidant effects of α-Tocopherol in improving motor and cognitive deficits induced by chronic reserpine in rats. Therefore, these data showed that α-Tocopherol could eliminate STZ-induced effects by using its antioxidant capacity and regulating glucose metabolism (as two proposed mechanisms), which is essential in improving cognition and memory function.…”

Section: Discussionmentioning

confidence: 99%

Pre- and post-treatment of α-Tocopherol on cognitive, synaptic plasticity, and mitochondrial disorders of the hippocampus in icv-streptozotocin-induced sporadic Alzheimer’s-like disease in male Wistar rat

et al. 2023

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ObjectiveMost dementia cases in the elderly are caused by Alzheimer’s disease (AD), a complex, progressive neurological disease. Intracerebroventricular (ICV) administration of streptozotocin (STZ) in rat’s results in aberrant brain insulin signaling, oxidative stress, and mitochondrial dysfunction that impair cognition change neural plasticity, and eventually lead to neuronal death. The current study aims to define the neuroprotective action of alpha-tocopherol in enhancing mitochondrial function and the function of synapses in memory-impaired rats brought on by icv-STZ.MethodsMale Wistar rats were pre-treated with (α-Tocopherol 150 mg/kg) orally once daily for 7 days before and 14 days after being bilaterally injected with icv-STZ (3 mg/kg), while sham group rats received the same volume of STZ solvent. After 2 weeks of icv-STZ infusion, rats were tested for cognitive performance using a behaviors test and then were prepared electrophysiology recordings or sacrificed for biochemical and histopathological assays.ResultsThe cognitive impairment was significantly minimized in the behavioral paradigms for those who had taken α-Tocopherol. In the hippocampus of icv-STZ rat brains, α-Tocopherol ocopherol effectively prevented the loss of glutathione levels and superoxide dismutase enzyme activity, lowered mitochondrial ROS and mitochondrial membrane potential, and also brought about a decrease in Aβ aggregation and neuronal death.ConclusionOur findings demonstrated that by lowering neurobehavioral impairments caused by icv-STZ, oxidative stress, and mitochondrial dysfunction, α-Tocopherol enhanced intracellular calcium homeostasis and corrected neurodegenerative defects in the brain. These findings examine the available approach for delaying AD connected to mitochondrial malfunction and plasticity issues.

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“…The animal model of PD proposed by Fernandes et al (2012) is induced by repeated administrations of a low dose (0.1 mg/kg) of reserpine. This protocol induces progressive motor changes (catalepsy, decreased spontaneous motor activity and oral dyskinesia), in addition to non-motor signs and neuronal changes compatible with the pathophysiology of PD in both rats (Fernandes et al, 2012;Santos et al, 2013;Sarmento-Silva, 2015;Brandão et al, 2017;Leão et al, 2017;Lins et al, 2017) and mice (Campêlo et al, 2017;Beserra-Filho et al, 2019). Recent adaptations of this protocol have also shown the applicability of reserpine in the study of several aspects of parkinsonism (Pereira et al, 2020;Rahman et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats

et al. 2022

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Parkinson’s disease (PD) is characterized by motor and non-motor signs, which are accompanied by progressive degeneration of dopaminergic neurons in the substantia nigra. Although the exact causes are unknown, evidence links this neuronal loss with neuroinflammation and oxidative stress. Repeated treatment with a low dose of reserpine—inhibitor of VMAT2—has been proposed as a progressive pharmacological model of PD. The aim of this study was to investigate whether this model replicates the neuroinflammation characteristic of this disease. Six-month-old Wistar rats received repeated subcutaneous injections of reserpine (0.1 mg/kg) or vehicle on alternate days. Animals were euthanized after 5, 10, or 15 injections, or 20 days after the 15th injection. Catalepsy tests (motor assessment) were conducted across treatment. Brains were collected at the end of each treatment period for immunohistochemical and RT-PCR analyzes. Reserpine induced a significant progressive increase in catalepsy duration. We also found decreased immunostaining for tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNpc) and increased GFAP + cells in the SNpc and dorsal striatum after 10 and 15 reserpine injections. Phenotyping microglial M1 and M2 markers showed increased number of CD11b + cells and percentage of CD11b + /iNOS + cells in reserpine-treated animals after 15 injections, which is compatible with tissue damage and production of cytotoxic factors. In addition, increased CD11b + /ArgI + cells were found 20 days after the last reserpine injection, together with an increment in IL-10 gene expression in the dorsal striatum, which is indicative of tissue repair or regeneration. Reserpine also induced increases in striatal interleukin TNF-alpha mRNA levels in early stages. In view of these results, we conclude that reserpine-induced progressive parkinsonism model leads to neuroinflammation in regions involved in the pathophysiology of PD, which is reversed 20 days after the last injection. These findings reveal that withdrawal period, together with the shift of microglial phenotypes from the pro-inflammatory to the anti-inflammatory stage, may be important for the study of the mechanisms involved in reversing this condition, with potential clinical applicability.

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Alpha-Tocopherol Counteracts Cognitive and Motor Deficits Induced by Repeated Treatment with Reserpine

Cited by 10 publications

References 61 publications

Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long‐Standing Model

Molecular, Neurochemical, and Behavioral Hallmarks of Reserpine as a Model for Parkinson's Disease: New Perspectives to a Long‐Standing Model

Pre- and post-treatment of α-Tocopherol on cognitive, synaptic plasticity, and mitochondrial disorders of the hippocampus in icv-streptozotocin-induced sporadic Alzheimer’s-like disease in male Wistar rat

Neuroinflammation in early, late and recovery stages in a progressive parkinsonism model in rats

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