MPTP toxicity causes vocal, auditory, orientation and movement defects in the echolocation bat

Wu, Wan Jhen; Lu, Chen Wen; Wang, Sheue Er; Lin, Ching Lung; Su, Li; Wu, Chung Hsin

doi:10.1097/wnr.0000000000001574

Cited by 3 publications

(3 citation statements)

References 40 publications

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“…MPTP is converted into MPP + , which can damage dopaminergic neurons in many mammals with biochemical and cellular changes that are relatively similar to those observed in PD [34]. Therefore, MPTP treatment is widely used to induce neural degeneration for the PD mice model.…”

Section: Discussionmentioning

confidence: 99%

Gastrodin ameliorated features of MPTP-induced Parkinson's disease via activating VMAT2 maintained dopamine homeostasis

Zhao

Xia

Wang

et al. 2022

Preprint

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The vesicular monoamine transporter (VMAT2) plays a crucial role in maintaining dopamine (DA) homeostasis through packaged DA into vesicles, which has been suggested to being an excellent marker for presynaptic dopaminergic nerve terminals in the nigrostriatal of Parkinson's disease. Gastrodin (GTD), the major bioactive compound of Gastrodia elata, has shown neuroprotective in animal models for many neurological disorders. However, it is unclear whether GTD confers neuroprotection via activating VMAT2 to maintain DA homeostasis in an animal model of Parkinson's disease (PD) using the DA neuron-specific toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we first identified that GTD could ameliorate cell damage and the dysfunction of DA homeostasis in PC12 cells induced by MPTP via up-regulating VMAT2 expression. Moreover, GTD could enhance VMAT2 protein expression, increase striatal vesicle volume, and ameliorate DA dysregulation in MPTP-induced PD mice. Furthermore, we found that the DA homeostasis and therapeutic effect of GTD could be reversed by the VMAT2 inhibitor in vitro and in vivo. Finally, we confirmed that GTD could increase VMAT2 expression by activating MEK/ERK pathway. In summary, our data showed that GTD attenuated MPTP neurotoxicity through activating of the MEK/ERK/VMAT2 signaling pathway maintained DA homeostasis, suggesting that the manipulation of VMAT2 by GTD may provide a potential therapeutic strategy for PD.

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Section: Discussionmentioning

confidence: 99%

Gastrodin ameliorated features of MPTP-induced Parkinson's disease via activating VMAT2 maintained dopamine homeostasis

Zhao

Xia

Wang

et al. 2022

Preprint

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“…DA neurons in the SNpc then selectively capture MPP+ from the intercellular space using the membrane transporter DAT due to its structural similarities to the dopamine molecule [ 93 ]. MPP+ accumulates in the mitochondria where it inhibits complex I of the electron transport chain, leading to the inhibition of cellular respiration [ 94 , 95 ], decreased ATP production [ 96 , 97 ], oxidative stress [ 98 , 99 ], the activation of the caspase cascade [ 100 ], and, ultimately, cell death.…”

Section: Parkinson’s Disease Is a Form Of Synucleinopathymentioning

confidence: 99%

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

et al. 2022

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Parkinson’s disease (PD) is one of the key neurodegenerative disorders caused by a dopamine deficiency in the striatum due to the death of dopaminergic (DA) neurons of the substantia nigra pars compacta. The initially discovered A53T mutation in the alpha-synuclein gene was linked to the formation of cytotoxic aggregates: Lewy bodies in the DA neurons of PD patients. Further research has contributed to the discovery of beta- and gamma-synucleins, which presumably compensate for the functional loss of either member of the synuclein family. Here, we review research from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity models and various synuclein-knockout animals. We conclude that the differences in the sensitivity of the synuclein-knockout animals compared with the MPTP neurotoxin are due to the ontogenetic selection of early neurons followed by a compensatory effect of beta-synuclein, which optimizes dopamine capture in the synapses. Triple-knockout synuclein studies have confirmed the higher sensitivity of DA neurons to the toxic effects of MPTP. Nonetheless, beta-synuclein could modulate the alpha-synuclein function, preventing its aggregation and loss of function. Overall, the use of knockout animals has helped to solve the riddle of synuclein functions, and these proteins could be promising molecular targets for the development of therapies that are aimed at optimizing the synaptic function of dopaminergic neurons.

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“…In this study, the protein expression of SOD2, TNF-α, and caspase 3 in the liver tissue was assessed through Western blotting. Similar to our previous study [13][14][15][16], we homogenized and quantified liver tissues and then transferred them onto polyvinylidene difluoride membranes (GE Healthcare Life Sciences, Barrington, IL, USA). Antibodies against β-actin ( ermo Fisher Scientific), SOD2, TNF-α, and caspase 3 (Cell Signaling Technology) were detected, visualized, and quantified using ImageJ analysis software (version 1.48t, NIH, Wayne Rasband, Washington DC, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Traditional Chinese Medicine Yang-Gan-Wan Alleviated Experimental Hepatic Damage by Inhibiting Oxidation, Inflammation, and Apoptosis in Cell and Mouse Models

Yeh

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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A hepatoprotective medicine, Yang-Gan-Wan (YGW), was used to treat hepatic damage in cell and mouse models. We performed a 1,1-diphenyl-2- picrylhydrazyl (DPPH) assay and found that YGW exhibited a significantly high free radical scavenging ability. Furthermore, the results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that YGW treatment could alleviate lipopolysaccharide (LPS)-induced damage in Kupffer cells (liver macrophages). Enzyme-linked immunosorbent assay results demonstrated that YGW treatment could alleviate LPS-induced inflammation in Kupffer cells by inhibiting the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. By quantifying the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), we found that YGW treatment could alleviate hepatic damage and improve immunity in acetaminophen- (APAP-) treated mice by inhibiting the expression of ALT and AST. The findings of hematoxylin and eosin and Masson’s trichrome staining indicated that YGW treatment could alleviate hepatic damage and reduce collagen fiber formation in the liver tissue of APAP-treated mice. Furthermore, immunohistochemistry staining and Western blot results showed that YGW treatment could alleviate oxidative stress, inflammation, and apoptosis in the liver tissue of APAP-treated mice by enhancing superoxide dismutase 2 (SOD2) expression but inhibiting TNF-α and caspase 3 expression. Our results suggest that YGW treatment exerted hepatoprotective effects on LPS-treated Kupffer cells and APAP-treated mice by inhibiting oxidation, inflammation, and apoptosis.

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MPTP toxicity causes vocal, auditory, orientation and movement defects in the echolocation bat

Cited by 3 publications

References 40 publications

Gastrodin ameliorated features of MPTP-induced Parkinson's disease via activating VMAT2 maintained dopamine homeostasis

Gastrodin ameliorated features of MPTP-induced Parkinson's disease via activating VMAT2 maintained dopamine homeostasis

Synuclein Proteins in MPTP-Induced Death of Substantia Nigra Pars Compacta Dopaminergic Neurons

Traditional Chinese Medicine Yang-Gan-Wan Alleviated Experimental Hepatic Damage by Inhibiting Oxidation, Inflammation, and Apoptosis in Cell and Mouse Models

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