Atorvastatin improves motor function, anxiety and depression by NOX2-mediated autophagy and oxidative stress in MPTP-lesioned mice

Yan, Jize; Huang, Jiarui; Liu, Anran; Wu, Jiannan; Fan, Hua; Shen, Mengmeng; Lai, Xiaoyi; Ma, Hongxia; Sun, Wenjie; Yang, Juan; Xu, Yunqi

doi:10.18632/aging.202189

Cited by 20 publications

(12 citation statements)

References 23 publications

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“…In this model, the striatal contents of dopamine, dopamine metabolite dihydroxyphenylacetic acid (DOPAC), 5-HT, and 5-HIAA, were all decreased (Silva et al 2016 ). Another neurotoxin, MPTP, also increases depression-like behavior and decreases TH expression (Zhang et al 2016 ; Yan et al 2020 ). Further, upregulation of monoamine oxidase A (MAO-A) and a decrease in noradrenaline and 5-HT in hippocampus were shown in the brain of a-synuclein A53T transgenic mice (Li et al 2020a ).…”

Section: Depressionmentioning

confidence: 99%

Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson’s disease: clues to early diagnosis and effective treatment

2021

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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by movement dysfunction due to selective degeneration of dopaminergic neurons in the substantia nigra pars compacta. Non-motor symptoms of PD (e.g., sensory dysfunction, sleep disturbance, constipation, neuropsychiatric symptoms) precede motor symptoms, appear at all stages, and impact the quality of life, but they frequently go unrecognized and remain untreated. Even when identified, traditional dopamine replacement therapies have little effect. We discuss here the pathology of two PD-associated non-motor symptoms: olfactory dysfunction and depression. Olfactory dysfunction is one of the earliest non-motor symptoms in PD and predates the onset of motor symptoms. It is accompanied by early deposition of Lewy pathology and neurotransmitter alterations. Because of the correlation between olfactory dysfunction and an increased risk of progression to PD, olfactory testing can potentially be a specific diagnostic marker of PD in the prodromal stage. Depression is a prevalent PD-associated symptom and is often associated with reduced quality of life. Although the pathophysiology of depression in PD is unclear, studies suggest a causal relationship with abnormal neurotransmission and abnormal adult neurogenesis. Here, we summarize recent progress in the pathology of the non-motor symptoms of PD, aiming to provide better guidance for its effective management.

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Section: Depressionmentioning

confidence: 99%

Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson’s disease: clues to early diagnosis and effective treatment

2021

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“…Previous studies have shown that PINK-1/Parkin pathway is related to mitochondrial damage, Parkin translocation to damaged mitochondria induces mitochondrial autophagy Quinn et al, 2020). Common antioxidants can reduce oxidative stress damage, but they cannot eliminate the increase of misfolded α-synuclein and other proteins (Yan et al, 2020). Here, we found that Cannabidiol could increase the LC3 levels and decrease the protein expression of p62 and α-synuclein.…”

Section: Discussionmentioning

confidence: 63%

Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways

Kang

Yao

et al. 2021

Front. Cell. Neurosci.

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The protective effect of Cannabidiol on Parkinson’s disease (PD) has been found in recent study. However, the specific mechanism of the protective effect of Cannabidiol on PD nerve damage require further exploration. This study aims to investigate effect of Cannabidiol on MMP-induced Neural Cells (SH-SY5Y) mitochondrial dysfunction. MMP+ and Cannabidiol were used to treat SH-SY5Y cells, the cells viability was measured by MTT assay. The expression of Tyrosine hydroxylase (TH) in cells was measured by western blotting and Immunofluorescence staining. The relationship among Cannabidiol, Silent mating type information regulation 2 homolog-1 (SIRT1) and NOTCH signaling, NF-κB signaling was examined by western blotting. The effect of Cannabidiol on MMP+-induced mitochondrial dysfunction of SH-SY5Y cells was measured by western blotting. Cannabidiol alleviated loss of TH expression and cytotoxicity in the MPP+-induced SH-SY5Y cells. Further mechanistic investigation showed that Cannabidiol induced SH-SY5Y cells autophagy to protects cells from mitochondrial dysfunction by upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways. Taken together, Cannabidiol acts as a protector in PD.

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“…When co-administered with an opioid receptor antagonist (naloxone), the antidepressant effect of simvastatin was reduced, suggesting that opioid receptors could be involved in statin's mechanism of action [268]. Atorvastatin decreased depressive-like behaviors in several mouse models of depression by decreasing TNF-α, IL-1β, and NF-κB p65, or by increasing hippocampal BDNF [269][270][271].…”

Section: Cholesterol Biosynthesis Pathwaymentioning

confidence: 99%

Novel Pharmacological Approaches to the Treatment of Depression

Elias

Zhang

Manners

2022

Life

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Major depressive disorder is one of the most prevalent mental health disorders. Monoamine-based antidepressants were the first drugs developed to treat major depressive disorder. More recently, ketamine and other analogues were introduced as fast-acting antidepressants. Unfortunately, currently available therapeutics are inadequate; lack of efficacy, adverse effects, and risks leave patients with limited treatment options. Efforts are now focused on understanding the etiology of depression and identifying novel targets for pharmacological treatment. In this review, we discuss promising novel pharmacological targets for the treatment of major depressive disorder. Targeting receptors including N-methyl-D-aspartate receptors, peroxisome proliferator-activated receptors, G-protein-coupled receptor 39, metabotropic glutamate receptors, galanin and opioid receptors has potential antidepressant effects. Compounds targeting biological processes: inflammation, the hypothalamic-pituitary-adrenal axis, the cholesterol biosynthesis pathway, and gut microbiota have also shown therapeutic potential. Additionally, natural products including plants, herbs, and fatty acids improved depressive symptoms and behaviors. In this review, a brief history of clinically available antidepressants will be provided, with a primary focus on novel pharmaceutical approaches with promising antidepressant effects in preclinical and clinical studies.

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Atorvastatin improves motor function, anxiety and depression by NOX2-mediated autophagy and oxidative stress in MPTP-lesioned mice

Cited by 20 publications

References 23 publications

Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson’s disease: clues to early diagnosis and effective treatment

Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson’s disease: clues to early diagnosis and effective treatment

Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways

Novel Pharmacological Approaches to the Treatment of Depression

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