Alpha-Synuclein deficiency ameliorates chronic methamphetamine induced neurodegeneration in mice

Ding, Jiuyang; Hu, Shanshan; Meng, Yunle; Li, Chen; Huang, Jian; He, Yitong; Qiu, Pingming

doi:10.1016/j.tox.2020.152461

Cited by 21 publications

(19 citation statements)

References 56 publications

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“…Also, withdrawal from chronic or sub-chronic METH exposure induces anxiety and depression-like behaviors in several animal models ( McCoy et al, 2011 ; North et al, 2013 ). The dose and duration of chronic METH usage range from 2 to 10 mg/kg and 7 days to 8 weeks, respectively ( Ding et al, 2020 ). In addition, a binge dose (5–10 mg/kg × 4 at 2 h intervals) and the acute bolus drug administration (20–40 mg/kg) of METH have been employed frequently to study its neurotoxicity ( Zhu et al, 2006 ; Melega et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

“…Two batches of mice were administered 14 and 28 doses of 10 mg/kg METH injections (twice per day with 2-h interval) over 7 and 14 days, respectively. One batch was given four 15 mg/kg METH injections with 2-h interval for 3 days and one batch was given gradually increasing doses (2,2,5,5,5,5,10,10,10,10,15, and 15 mg/kg) of METH in 3 days (Martins et al, 2011;Ding et al, 2020;Chen et al, 2021). These experiments were all performed under NAT of 22 • C. The depression-like behaviors were tested 7 and 14 days after METH exposure.…”

Section: Effect Of Drug Exposure Regimen and Dose On Methamphetamine-induced Depression-like Behaviorsmentioning

confidence: 99%

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The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride

Wang

Tong

Hui

et al. 2022

Front. Mol. Neurosci.

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Methamphetamine (METH) abuse causes irreversible damage to the central nervous system and leads to psychiatric symptoms including depression. Notably, METH-induced hyperthermia is a crucial factor in the development of these symptoms, as it aggravates METH-induced neurotoxicity. However, the role of hyperthermia in METH-induced depression-like behaviors needs to be clarified. In the present study, we treated mice with different doses of METH under normal (NAT) or high ambient temperatures (HAT). We found that HAT promoted hyperthermia after METH treatment and played a key role in METH-induced depression-like behaviors in mice. Intriguingly, chronic METH exposure (10 mg/kg, 7 or 14 days) or administration of an escalating-dose (2 ∼ 15 mg/kg, 3 days) of METH under NAT failed to induce depression-like behaviors. However, HAT aggravated METH-induced damage of hippocampal synaptic plasticity, reaction to oxidative stress, and neuroinflammation. Molecular hydrogen acts as an antioxidant and anti-inflammatory agent and has been shown to have preventive and therapeutic applicability in a wide range of diseases. Coral calcium hydride (CCH) is a newly identified hydrogen-rich powder which produces hydrogen gas gradually when exposed to water. Herein, we found that CCH pretreatment significantly attenuated METH-induced hyperthermia, and administration of CCH after METH exposure also inhibited METH-induced depression-like behaviors and reduced the hippocampal synaptic plasticity damage. Moreover, CCH effectively reduced the activity of lactate dehydrogenase and decreased malondialdehyde, TNF-α and IL-6 generation in hippocampus. These results suggest that CCH is an efficient hydrogen-rich agent, which has a potential therapeutic applicability in the treatment of METH abusers.

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Section: Discussionmentioning

confidence: 99%

Section: Effect Of Drug Exposure Regimen and Dose On Methamphetamine-induced Depression-like Behaviorsmentioning

confidence: 99%

The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride

Wang

Tong

Hui

et al. 2022

Front. Mol. Neurosci.

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“…METH-induced α-syn accumulation directly leads to mitochondrial damage, myelin sheath degeneration, and failure to form synaptic vesicles, and can indirectly lead to the overexpression of CDK5, tau phosphorylation, and autophagy blockage. Both pathways can synergistically enhance the breakdown of neurons (Ding et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Moderate-intensity interval training (MIT) can protect rats against Methamphetamine –induced injuries

Bafti

Haghighi

Askari

et al. 2021

Preprint

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Methamphetamine (METH) can cause neurotoxicity and increase the risk of neurodegenerative disorders such as Alzheimer disease and Parkinson disease. This study aimed to investigate the effect of moderate-intensity interval training (MIT) on gene expression and antioxidant status of the hippocampus of METH-dependent rats. Twenty-eight male Wistar rats were randomly divided into four equal groups (n=7): saline, METH, MIT, and METH+MIT. METH was injected intraperitoneally at 5 mg/kg for 21 days. The MIT (intermittent running) was performed on the treadmill 5 days a week for 8 weeks. Morris Water Maze test was performed to measure learning and memory. Then, the hippocampal tissue was extracted to evaluate changes in gene expression and biochemical enzymes. The data were analyzed using one-way and two-way ANOVA methods at P<0.05. The results showed that METH injection significantly reduced spatial memory and antioxidant enzymes and increased the expression of α-synuclein (α-syn), cyclin-dependent kinase 5 (CDK5), tau and phosphorylated tau (p-Tau) genes compared to the saline group. MIT significantly increased spatial memory and antioxidant enzymes. However, it reduced α-syn, CDK5, tau and p-tau expression. Thus, METH caused neural damage, and MIT could protect the neural system against METH-induced insults in male rats.

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“…A recent study indicated that the METH treatment upregulated a-syn in neurons, which may directly induce mitochondrial damage, myelin sheath destruction, and synaptic failure. The excess a-syn might also indirectly promote tau phosphorylation through tau kinase, glycogen synthase kinase 3 beta (GSK3b) and cyclindependent kinase 5 (CDK5), leading to microtubule depolymerization and eventually fusion deficit of autophagosome and lysosome (Ding et al 2020). Other studies reported that METH affected the expression of many lysosome proteins, such as lysosomal integral membrane protein type-2 (LIMP-2) (Li et al 2018), microtubule-associated protein 1 light chain 3 (LC3) (Zhao et al 2018), lysosome-associated membrane proteins (LAMPS), and suppressed the activity of cathepsin L (Nara et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Methamphetamine leads to the alterations of microRNA profiles in the nucleus accumbens of rats

Yang

Hong

et al. 2020

Pharmaceutical Biology

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Context: MicroRNA (miRNA) is an important regulator of gene expression. Methamphetamine (METH) induces a variety of alterations in different systems by affecting gene expression, but the effects of METH on miRNA profiles need to be elucidated. Objectives: This study develops a rat model of METH addiction, and analyzes the expression profile alterations of miRNA in nucleus accumbens (NAc) of the METH-addicted rats. Materials and methods: Sprague-Dawley rats were administered 10 mg/kg METH or vehicle twice a day for 4 weeks. The addictive behaviour of rats was estimated by CPP test. The pathological changes of brain tissues were then observed by HE and Glee silver staining. The miRNA profile analysis of the NAc of the rats was performed using an Illumina HiSeq TM 2500 sequencing system. Results: CPP test indicated that METH significantly prolonged the residence time of the rats in the drug box (from 307 ± 97 to 592 ± 96 s). The pathological staining showed the distorted axons, and fewer polarized neurons in the METH-treated rats. We further identified 40 differential miRNAs (17 up-and 23 downregulated) and three novel miRNAs (novel 237, 296 and 501) that responded to METH. The bioinformatic analysis for the potential targets of the differential miRNA suggests that the downstream were concentrated in the Wnt signalling pathway, tuberculosis, toxoplasmosis, spliceosome, lysosome, and axon guidance. Discussion and conclusions: A number of miRNAs responding to METH were identified in the NAc of rats. These METH-regulated miRNAs provide a new perspective for revealing the molecular mechanisms of METH addiction.

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Alpha-Synuclein deficiency ameliorates chronic methamphetamine induced neurodegeneration in mice

Cited by 21 publications

References 56 publications

The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride

The Role of Hyperthermia in Methamphetamine-Induced Depression-Like Behaviors: Protective Effects of Coral Calcium Hydride

Moderate-intensity interval training (MIT) can protect rats against Methamphetamine –induced injuries

Methamphetamine leads to the alterations of microRNA profiles in the nucleus accumbens of rats

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