Temporal development of neurochemical and cognitive impairments following reserpine administration in rats

Pereira, Alice Theresinha Cybis; Poli, Anicleto; Matheus, Filipe C.; Silva, Lucila de Bortoli da; Fadanni, Guilherme Pasetto; Izídio, Geison S.; Latini, Alexandra; Prediger, Rui Daniel

doi:10.1016/j.bbr.2020.112517

Cited by 11 publications

(6 citation statements)

References 27 publications

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“…In the study, a significant decrease in social interaction and object recognition behavior was observed 3 h after reserpine administration. 7 In general, drug discovery research is highly time and costintensive. Since long, researchers have been using rodents as the translational animal models.…”

Section: Introductionmentioning

confidence: 99%

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by¹H Nuclear Magnetic Resonance-Based Metabolomics

et al. 2021

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Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1 H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1 H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and c-amino butyric acid (GABA), b-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.

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Section: Introductionmentioning

confidence: 99%

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by¹H Nuclear Magnetic Resonance-Based Metabolomics

et al. 2021

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“…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). In this study, we sought to extend the validation of this protocol, by verifying if neuroinflammation is induced concomitantly to the other alterations related to PD pathophysiology seen in previous studies (decreased dopaminergic markers, increased alpha-synuclein and oxidative stress).…”

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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“…23 As per the study of Periera et al (2020) reduction in straiatal dopamine levels and short-term memory impairments are seen after Reserpine administration in rats which mimics the pre-motor phase of Parkinson's disease. 24 Dopamine depletion causes hypersensitivity of D2 receptors in corticostriatal terminals hence dopamine metabolism results in reduced dopamine release in synaptic cleft shows early and late impairment in behavior and social recognition tasks (Periera et al 2020). 24 Dopamine and 5 hydroxy tryptamine are responsible for regulation of mood in brain, however our study reveals that improved in locomotion activity with Camelia sinensis was might be due to its effect on increased levels of 5 hydroxy tryptamine in brain region.…”

Section: Discussionmentioning

confidence: 99%

“…24 Dopamine depletion causes hypersensitivity of D2 receptors in corticostriatal terminals hence dopamine metabolism results in reduced dopamine release in synaptic cleft shows early and late impairment in behavior and social recognition tasks (Periera et al 2020). 24 Dopamine and 5 hydroxy tryptamine are responsible for regulation of mood in brain, however our study reveals that improved in locomotion activity with Camelia sinensis was might be due to its effect on increased levels of 5 hydroxy tryptamine in brain region. 25 In present study we observe that the extract of Camelia sinensis significantly shows improvements in haloperidol induced catalepsy, reserpine induced hypolocomotion and tacrine induced vacuous chewing movements and are due to the direct or indirect effect of chemical constituents present in extract.…”

Section: Discussionmentioning

confidence: 99%

Antiparkinsonian and Antioxidant Effects of Hydroalcoholic Extract of Camellia sinensis, Asparagus racemosus, Mucuna pruriens and their Combination

Giri¹,

Bhalke

Prakash³

et al. 2020

IJPI

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Temporal development of neurochemical and cognitive impairments following reserpine administration in rats

Cited by 11 publications

References 27 publications

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by¹H Nuclear Magnetic Resonance-Based Metabolomics

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by¹H Nuclear Magnetic Resonance-Based Metabolomics

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

Antiparkinsonian and Antioxidant Effects of Hydroalcoholic Extract of Camellia sinensis, Asparagus racemosus, Mucuna pruriens and their Combination

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Temporal development of neurochemical and cognitive impairments following reserpine administration in rats

Cited by 11 publications

References 27 publications

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by1H Nuclear Magnetic Resonance-Based Metabolomics

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by1H Nuclear Magnetic Resonance-Based Metabolomics

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

Antiparkinsonian and Antioxidant Effects of Hydroalcoholic Extract of Camellia sinensis, Asparagus racemosus, Mucuna pruriens and their Combination

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Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by¹H Nuclear Magnetic Resonance-Based Metabolomics

Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by¹H Nuclear Magnetic Resonance-Based Metabolomics