TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways
Methamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant te...
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doaj-11a5c505db9b4c14878fddc14ef257572020-11-25T03:05:54ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942020-01-01202010.1155/2020/87871568787156TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling PathwaysXianyi Meng0Chenghong Zhang1Yu Guo2Ying Han3Chunyang Wang4Haiying Chu5Li Kong6Haiying Ma7Department of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaDepartment of Histology and Embryology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, ChinaMethamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant tertiary butylhydroquinone (TBHQ) can alleviate neurotoxicity through both antioxidative stress and antiapoptotic signaling pathways in the VTA. Rats were randomly divided into a control group, a METH-treated group (METH group), and a METH+TBHQ-treated group (METH+TBHQ group). Intraperitoneal injections of METH at a dose of 10 mg/kg were administered to the rats in the METH and METH+TBHQ groups for one week, and METH was then administered at a dose that increased by 1 mg/kg per week until the sixth week, when the daily dosage reached 15 mg/kg. The rats in the METH+TBHQ group received 12.5 mg/kg TBHQ intragastrically. Chronic exposure to METH resulted in increased immobility times in the forced swimming test (FST) and tail suspension test (TST) and led to depression-like behavior. The production of reactive oxygen species (ROS) and apoptosis levels were increased in the VTA of animals in the METH-treated group. METH downregulated Nrf2, HO-1, PI3K, and AKT, key factors of oxidative stress, and the apoptosis signaling pathway. Moreover, METH increased the caspase-3 immunocontent. These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity.http://dx.doi.org/10.1155/2020/8787156 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xianyi Meng Chenghong Zhang Yu Guo Ying Han Chunyang Wang Haiying Chu Li Kong Haiying Ma |
spellingShingle |
Xianyi Meng Chenghong Zhang Yu Guo Ying Han Chunyang Wang Haiying Chu Li Kong Haiying Ma TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways Oxidative Medicine and Cellular Longevity |
author_facet |
Xianyi Meng Chenghong Zhang Yu Guo Ying Han Chunyang Wang Haiying Chu Li Kong Haiying Ma |
author_sort |
Xianyi Meng |
title |
TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways |
title_short |
TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways |
title_full |
TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways |
title_fullStr |
TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways |
title_full_unstemmed |
TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways |
title_sort |
tbhq attenuates neurotoxicity induced by methamphetamine in the vta through the nrf2/ho-1 and pi3k/akt signaling pathways |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0900 1942-0994 |
publishDate |
2020-01-01 |
description |
Methamphetamine (METH) leads to nervous system toxicity. Long-term exposure to METH results in damage to dopamine neurons in the ventral tegmental area (VTA), and depression-like behavior is a clinical symptom of this toxicity. The current study was designed to investigate whether the antioxidant tertiary butylhydroquinone (TBHQ) can alleviate neurotoxicity through both antioxidative stress and antiapoptotic signaling pathways in the VTA. Rats were randomly divided into a control group, a METH-treated group (METH group), and a METH+TBHQ-treated group (METH+TBHQ group). Intraperitoneal injections of METH at a dose of 10 mg/kg were administered to the rats in the METH and METH+TBHQ groups for one week, and METH was then administered at a dose that increased by 1 mg/kg per week until the sixth week, when the daily dosage reached 15 mg/kg. The rats in the METH+TBHQ group received 12.5 mg/kg TBHQ intragastrically. Chronic exposure to METH resulted in increased immobility times in the forced swimming test (FST) and tail suspension test (TST) and led to depression-like behavior. The production of reactive oxygen species (ROS) and apoptosis levels were increased in the VTA of animals in the METH-treated group. METH downregulated Nrf2, HO-1, PI3K, and AKT, key factors of oxidative stress, and the apoptosis signaling pathway. Moreover, METH increased the caspase-3 immunocontent. These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity. |
url |
http://dx.doi.org/10.1155/2020/8787156 |
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