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Reserpine induced PD-like motor symptoms in mice. (A) Flow chart of the experimental design. (B) Changes in body weights of mice induced by different doses of reserpine (n = 7 for each group, two-way ANOVA with Tukey's post hoc test). (C) The movement time of mice decreased upon induction with different doses of reserpine in the rotarod test (n = 7 for each group, two-way ANOVA with Tukey's post hoc test, **p < 0.01, ***p < 0.001 vs. control). (D) The latency time of mice increased upon induction with different doses of reserpine in the pole-climbing test (n = 7 for each group, two-way ANOVA with Tukey's post hoc test, *p < 0.05, **p < 0.01, ***p < 0.001 vs. control). (E) Moved distances reduced in the openfield test upon induction with different doses of reserpine (n = 7 for each group, two-way ANOVA with Tukey's post hoc test, *p < 0.05, **p < 0.01, ***p < 0.001 vs. control). (F) Representative plots for the movement trajectory. All data are presented as mean ± SEM; Con, control; RES, reserpine.
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Reserpine is an effective drug for the clinical treatment of hypertension. It also induces Parkinson’s disease (PD)-like symptoms in humans and animals possible through the inhibition of monoamine vesicular transporters, thus decreasing the levels of monoamine neurotransmitters in the brain. However, the precise mechanisms remain unclear. Herein, w...
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... 1987). We modified this method by oral administration of different concentrations of reserpine in the drinking water for 12 weeks to establish a preclinical PD mouse model ( Figure 5A). ...
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... in Pharmacology frontiersin.orgweights were observed between the reserpine-treated and the control mice ( Figure 5B). No significant differences in the motor functions of the mice between the lowest dose of reserpine (0.9 μg/ml)-treated and control groups were observed. ...
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... the rotarod test, the total movement time significantly decreased in both 3 μg/ml and 9 μg/ ml reserpine-treated groups (two-way ANOVA, F Dose (12,312) = 9.932, p < 0.0001; F Time (3,312) = 118.1, p < 0.0001; F Interaction (36,312) = 5.176, p < 0.0001; Figure 5C). In the pole-climbing test, the latency time was significantly prolonged in the 3 μg/ml and 9 μg/ml reserpine-treated groups (two-way ANOVA, F Dose (12,455) = 9.674, p < 0.0001; F Time (3,455) = 195.2, ...
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... the pole-climbing test, the latency time was significantly prolonged in the 3 μg/ml and 9 μg/ml reserpine-treated groups (two-way ANOVA, F Dose (12,455) = 9.674, p < 0.0001; F Time (3,455) = 195.2, p < 0.0001; F Interaction (36,455) = 4.751, p < 0.0001; Figure 5D). In the open field test, the total movement distance showed a significant reduction in both 3 μg/ml and 9 μg/ml reserpine-treated groups (two-way ANOVA, F Dose (12,312) = 7.376, p < 0.0001; F Time (3,312) = 71.69, ...
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... the open field test, the total movement distance showed a significant reduction in both 3 μg/ml and 9 μg/ml reserpine-treated groups (two-way ANOVA, F Dose (12,312) = 7.376, p < 0.0001; F Time (3,312) = 71.69, p < 0.0001; F Interaction (36,312) = 1.143, p = 0.2700; Figure 5E). A representative graph of the track at week 12 is shown in Figure 5F. ...
Citations
... Moreover, searching with rare metabolites, such as reserpine was detected in 0.010% of the samples (Supplementary Figure S3). Reserpine is a drug that is used clinically to treat illnesses such as hypertension and Parkinson's disease 44 . It was isolated for the first time from the plant Rauvolfia (=Rauwolfia) serpentina (Apocynaceae) and plays a role by blocking noradrenaline, dopamine, and serotonin reuptake in nerve cells, resulting in relaxing and blood pressure-lowering effects 45 . ...
Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.
... Given the dopamine depleting effects of reserpine and the known co-morbidity of depression and anxiety, we extended our analysis to the open field test. Reserpine at 1 mg/kg dose in our study did not reduce overall traveled distance or speed suggesting that dopamine signaling still acts to perform motor activity primarily via striatum [31]. In addition, no significant effects were observed in the time spent at the center between the R and C groups strengthening the notion that lack of complete dopamine depletion may explain no notable effects on anxiety-like behaviors. ...
Introduction: Due to lack of effective and fast-acting therapy, depression can become a life-threatening condition if not treated adequately. In fibromyalgia animal models, pregabalin has shown antidepressant properties. Compared to fluoxetine, the unusual fast-acting antidepressant properties of pregabalin offers the possibility to explore this GABA analogue in the context of depression. Objective: we evaluated the acute effect of pregabalin in a reserpine-induced animal models of depression. Method: rats were organized into four groups regarding their planned drug regimen: control (C), reserpine (R), reserpine + fluoxetine (RF) and reserpine + pregabalin (RP). The C group received only saline throughout the study. Depressive and anxiety-like behavior were tested using the force swimming test (FST) and the open field test (OFT), respectively. Results: Our data shows that both RP and RF groups have a significant longer mobility time (seconds) than the C group during the FST (RP: 44.76 ± 8.37 and RF: 65.86 ± 34.10 vs C: 21.80 ± 11.10, p<0.05 for both). No significant differences were observed in immobility time and climbing across all groups (p>0.05). On the other hand, RF and RP groups showed a reduced time spent in the center of the arena compared to control (p<0.05) in
... We sought in the present work to investigate the efficacy of PBM to alleviate motor deficits, oxidative stress, enzymatic inhibition/activation, and decreased monoamine levels induced by reserpine in two PD-related brain regions: midbrain and striatum. Reserpine induces PD symptoms in animals via the disruption of monoamine transport into synaptic vesicles by blocking the vesicular monoamine transporter (VMAT), which is responsible for the transport of DA, 5-HT, and NE into synaptic vesicles [45], thus decreasing the availability of these neurotransmitters in the synaptic cleft and causing motor and non-motor symptoms of PD [46]. In addition, C reserpine has been shown to decrease mitochondrial respiration and ATP production, as well as increase oxidative stress and mitochondrial DNA damage [47]. ...
Photobiomodulation (PBM) of deep brain structures through transcranial infrared irradiation might be an effective treatment for Parkinson’s disease (PD). However, the mechanisms underlying this intervention should be elucidated to optimize the therapeutic outcome and maximize therapeutic efficacy. The present study aimed at investigating the oxidative stress-related parameters of malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) and the enzymatic activities of sodium–potassium-ATPase (Na ⁺ , K ⁺ -ATPase), Acetylcholinesterase (AChE), and monoamine oxidase (MAO) and monoamine levels (dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the midbrain and striatum of reserpine-induced PD in an animal model treated with PBM. Furthermore, the locomotor behavior of the animals has been determined by the open field test. Animals were divided into three groups; the control group, the PD-induced model group, and the PD-induced model treated with the PBM group. Non-invasive treatment of animals for 14 days with 100 mW, 830 nm laser has demonstrated successful attainment in the recovery of oxidative stress, and enzymatic activities impairments induced by reserpine (0.2 mg/kg) in both midbrain and striatum of adult male Wistar rats. PBM also improved the decrease in DA, NE, and 5-HT in the investigated brain regions. On a behavioral level, animals showed improvement in their locomotion activity. These findings have shed more light on some mechanisms underlying the treatment potential of PBM and displayed the safety, easiness, and efficacy of PBM treatment as an alternative to pharmacological treatment for PD.
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... Venlafaxine, as an antidepressant, may inhibit HDAC6 expression by further enhancing autophagy markers (beclin-1, p62 and LC3) and restoring histidine-3 acetylation, thereby suppressing depressive symptoms (El-Saiy et al. 2022). Chronic reserpine exposure increased the LC3-II/LC3-I ratio and p62 expression in the substantia nigra of mice, leading to depression-like behavior (Li et al. 2022). These findings suggested a close association between LC3 and p62 with the development of depressive symptoms in PD. ...
Depressive symptoms are common in Parkinson’s disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50–80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = – 0.002, t = − 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = − 0.001, t = − 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall.
... Recent studies have discovered a downregulation of autophagic components, including Lc3, Beclin-1, p62 and ATG5, in peripheral blood cells of patients with Pd (46,47). Abnormal expression of these autophagy-related proteins in the SN of Pd-related mice is accompanied by both upregulated α-synuclein and clinical symptoms, such as constipation, olfactory impairment and depression-like behaviors (48). Therefore, these findings indicate that autophagy is involved in the pathological process of Pd. ...
Parkinson's disease (PD) is a neurodegenerative disorder that has a high incidence during the aging process and is characterized by the loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunctions and non‑motor symptoms. Impaired clearance and excessive accumulation of aberrantly modified proteins or damaged organelles, such as aggregated α‑synuclein and dysfunctional mitochondria, are regarded as the main causes of nigrostriatal neurodegeneration. As one of the major degradation pathways, autophagy can recycle these useless or toxic substances to maintain cellular homeostasis and it plays a crucial role in PD progression. MicroRNAs (miRNAs) are a group of small non‑coding RNA molecules that regulate gene expression by silencing targeted mRNAs. Recent studies have illustrated that autophagy‑regulating miRNA has been implicated in pathological processes of PD, including α‑synuclein accumulation, mitochondrial damage, neuroinflammation and neuronal apoptosis, which suggests that targeting autophagy‑regulating miRNAs may provide novel therapeutic strategies for this disease. The present review summarizes the role of autophagy in PD and emphasizes the role of miRNA‑mediated autophagy in PD, for the development of promising interventions in this disease.
... Recently, Li et al. (2022) demonstrated that reserpine induced motor and non-motor symptoms similar to PD. The authors found that reserpine caused alpha-synuclein deposition, autophagy impairment and tyrosine hydroxylase reduction in the substantia nigra and proposed reserpine model as a valuable tool in PD studies. ...
... The repeated administration of a low dose of reserpine results in a progressive appearance of motor symptoms in rats which supports the use of reserpine to induce PD animal models (Fernandes et al. 2012;Li et al. 2022). These motor impairments are accompanied by an enhanced oxidative stress which has been implicated as a possible pathophysiological mechanism in PD (Gaki and Papavassiliou 2014;de Farias et al. 2016]. ...
Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease worldwide and represents a challenge for clinicians. The present study aims to investigate the effects of cerebrolysin and/or lithium on the behavioral, neurochemical and histopathological alterations induced by reserpine as a model of PD. The rats were divided into control and reserpine-induced PD model groups. The model animals were further divided into four subgroups: rat PD model, rat PD model treated with cerebrolysin, rat PD model treated with lithium and rat PD model treated with a combination of cerebrolysin and lithium. Treatment with cerebrolysin and/or lithium ameliorated most of the alterations in oxidative stress parameters, acetylcholinesterase and monoamines in the striatum and midbrain of reserpine-induced PD model. It also ameliorated the changes in nuclear factor-kappa and improved the histopathological picture induced by reserpine. It could be suggested that cerebrolysin and/or lithium showed promising therapeutic potential against the variations induced in the reserpine model of PD. However, the ameliorating effects of lithium on the neurochemical, histopathological and behavioral alterations induced by reserpine were more prominent than those of cerebrolysin alone or combined with lithium. It can be concluded that the antioxidant and anti-inflammatory effects of both drugs played a significant role in their therapeutic potency.
Depression is one of the common non-motor symptoms of Parkinson's disease (PD). In the clinic, botulinum neurotoxin A (BoNT/A) has been used to treat depression. In this study, we investigated the mechanisms underlying the anti-depressive effect of BoNT/A in a PD mouse model. Mice were administered reserpine (3 μg/mL in the drinking water) for 10 weeks. From the 10th week, BoNT/A (10 U·kg-1·d-1) was injected into the cheek for 3 consecutive days. We showed that chronic administration of reserpine produced the behavioral phenotypes of depression and neurochemical changes in the substantia nigra pars compacta (SNpc) and striatum. BoNT/A treatment significantly ameliorated the depressive-like behaviors, but did not improve TH activity in SNpc of reserpine-treated mice. We demonstrated that BoNT/A treatment reversed reserpine-induced complement and microglia activation in the hippocampal CA1 region. Furthermore, BoNT/A treatment significantly attenuated the microglial engulfment of presynaptic synapses, thus ameliorating the apparent synapse and spine loss in the hippocampus in the reserpine-treated mice. Moreover, BoNT/A treatment suppressed microglia-mediated expression of pro-inflammatory cytokines TNF-α and IL-1β in reserpine-treated mice. In addition, we showed that BoNT/A (0.1 U/mL) ameliorated reserpine-induced complement and microglia activation in mouse BV2 microglial cells in vitro. We conclude that BoNT/A ameliorates depressive-like behavior in a reserpine-induced PD mouse model through reversing the synapse loss mediated by classical complement induced-microglial engulfment as well as alleviating microglia-mediated proinflammatory responses. BoNT/A ameliorates depressive-like behavior, and reverses synapse loss mediated by classical complement pathway-initiated microglia engulfment as well as alleviates microglia-mediated proinflammatory response in the reserpine-induced Parkinson's disease mouse model.
