The toxic influence of paraquat on hippocampal neurogenesis in adult mice

Li, Kaikai; Cheng, Xinran; Jiang, Jinhua; Wang, Jiutao; Xie, Jiongfang; Xiu, Hu; Huang, Yingxue; Song, Lingzhen; Liu, Mengmeng; Cai, Leiming; Chen, Liezhong; Zhao, Shanting

doi:10.1016/j.fct.2017.05.067

Cited by 34 publications

(13 citation statements)

References 45 publications

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“…Impairment of adult neurogenesis specifically exacerbates AD neuropathology in APPswe/PS1ΔE9 AD trangenic mice [ 150 ]. In this connection, Paraquat has been specifically shown to inhibit hippocampal neurogenesis in adult mice, as intraperitoneal administration of the compound for 3 weeks inhibited neural progenitor cell proliferation, altered developmental fate of newly generated cells in the hippocampus and impaired hippocampus-dependent learning and memory [ 153 ]. Perinatal exposure of the herbicide glufosinate-ammonium (GLA) to pregnant mothers inhibits SVG neurogenesis in newborn mice and altered the neuro-glial differentiation of cultured mouse primary neural stem cells [ 154 , 155 ].…”

Section: Speculative Neuropathological Mechanisms Of Pesticidesmentioning

confidence: 99%

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

Tang

2020

Toxics

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Environmental toxicants have been implicated in neurodegenerative diseases, and pesticide exposure is a suspected environmental risk factor for Alzheimer’s disease (AD). Several epidemiological analyses have affirmed a link between pesticides and incidence of sporadic AD. Meanwhile, in vitro and animal models of AD have shed light on potential neuropathological mechanisms. In this paper, a perspective on neuropathological mechanisms underlying pesticides’ induction of AD is provided. Proposed mechanisms range from generic oxidative stress induction in neurons to more AD-specific processes involving amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau). Mechanisms that are more speculative or indirect in nature, including somatic mutation, epigenetic modulation, impairment of adult neurogenesis, and microbiota dysbiosis, are also discussed. Chronic toxicity mechanisms of environmental pesticide exposure crosstalks in complex ways and could potentially be mutually enhancing, thus making the deciphering of simplistic causal relationships difficult.

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Section: Speculative Neuropathological Mechanisms Of Pesticidesmentioning

confidence: 99%

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

Tang

2020

Toxics

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“…In supervised trials, PQ has been detected in many farm products (Francesquett et al, ; Lei, Li, Chen, & Xu, ; Zhang et al, ), and epidemiological investigation found that PQ even exists in neonatal meconium (Konthonbut et al, ), highlighting the need to study the adverse effects of PQ on the health of the general population. Owing to the structural similarity with the neurotoxicant MPP+ and induction of oxidative stress (Cocheme & Murphy, ), the neurotoxicity of PQ on human as well as animal models has been generally accepted (Costello, Cockburn, Bronstein, Zhang, & Ritz, ; Li et al, ; Tanner et al, ).…”

Section: Introductionmentioning

confidence: 99%

N‐acetylcysteine alleviated paraquat‐induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells

Xiong

Zhao

Yan

et al. 2019

J of Applied Toxicology

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The developing brain is uniquely vulnerable to toxic chemical exposures. Studies indicate that neural stem cell (NSC) self‐renewal is susceptible to oxidative stress caused by xenobiotics. However, the impact of antioxidants on NSC self‐renewal and the potential mechanisms remain elusive. In this study, primary murine neural progenitor cells (mNPCs) from the subventricular zone were used as a research model. In addition, paraquat (PQ) was used to elicit oxidative stress and N‐acetylcysteine (NAC) was used as a powerful antioxidant. mNPCs were treated with 80 μm PQ for 24 hours with or without 4 hours of NAC pretreatment. Our results showed that PQ treatment increased intracellular reactive oxygen species production, decreased cell viability and DNA synthesis, and promoted cell apoptosis. Meanwhile, pretreatment with NAC alleviated PQ‐induced cytotoxicity in mNPCs. To elucidate the mechanisms further, we found that NAC pretreatment prevented PQ‐induced reactive oxygen species production, mitochondrial fragmentation and autophagy in mNPCs. NAC‐pretreated cells showed increased anti‐apoptotic protein Bcl‐2 and decreased pro‐apoptotic protein Bax expression. Similarly, NAC pretreatment increased p‐mTOR and decreased LC3B‐II protein expression. Moreover, NAC decreased mitophagy related mRNA Pink1 and Parkin expression. Taken together, our results suggested that the antioxidant NAC treatment significantly attenuated PQ‐induced mNPC self‐renewal disruption through decreasing autophagy and salvaging mitochondrial morphology. These findings revealed a potential mechanism for neurological treatment relating to antioxidant and suggested potentially relevant implications for PQ‐related neurodegenerative disorders. Thus, our study also provided insight into therapeutic strategies for the neurotoxic effects of oxidative stress‐associated toxicants.

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“…The pro-inflammatory cytokines in SGZ and SVZ, including IL-6, IL-1β, TNF-α, were significantly increased in mice treated with 20 mg/kg PQ, indicating that the neuroinflammation indeed occurred. Previously, others and we reported that PQ-induced damages of brain function were associated with neuroinflammation, increased ROS and mitochondrial dysfunction 14,[38][39][40] . Upon environmental stresses, neuroinflammation could be induced by microglia and/ or astrocytes which were regarded as the main pro-inflammatory cytokines secreting cells in the brain 28 .…”

Section: Discussionmentioning

confidence: 74%

Endoplasmic reticulum stress-related neuroinflammation and neural stem cells decrease in mice exposure to paraquat

Yang

Shao

Zhao

et al. 2020

Sci Rep

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Paraquat (PQ), a widely used herbicide, could cause neurodegenerative diseases, yet the mechanism remains incompletely understood. This study aimed to investigate the direct effect of PQ on NSC in vivo and its possible mechanism. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control once a week for 2 weeks, and sacrificed 1 week after the last PQ injection. Furthermore, extra experiments with Tauroursodeoxycholic Acid (TUDCA) intervention were performed to observe the relationship between ER stress, neuroinflammation and the neural stem cell (NSC) impairment. The results showed that 20 mg/kg PQ caused the NSC number decrease in both subgranular zones (SGZ) and subventricular zone (SVZ). Further analysis indicated that the 20 mg/kg PQ suppressed the proliferation of NSC, without affecting the apoptosis. Moreover, 20 mg/kg PQ also induced ER stress in microglia and caused neuroinflammation in SGZ and SVZ. Interestingly, the ER stress inhibitor could simultaneously ameliorate the neuroinflammation and NSC reduction. These data suggested that increased ER stress in microglia might be a possible pathway for PQ-induced neuroinflammation and NSC impairment. That is a previously unknown mechanism for PQ neurotoxicity.

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The toxic influence of paraquat on hippocampal neurogenesis in adult mice

Cited by 34 publications

References 45 publications

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

Neuropathological Mechanisms Associated with Pesticides in Alzheimer’s Disease

N‐acetylcysteine alleviated paraquat‐induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells

Endoplasmic reticulum stress-related neuroinflammation and neural stem cells decrease in mice exposure to paraquat

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