Lead, cadmium, arsenic, and mercury combined exposure disrupted synaptic homeostasis through activating the Snk-SPAR pathway

Lee

2021

IJERPH

Environmental exposure to arsenic (As), lead (Pb), and cadmium (Cd) frequently occurs; however, data on the specific effects of combined exposure on neurotransmission, specifically dopaminergic neurotransmission, are lacking. In this study, motor coordination and dopamine content, along with the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors (DRs), were examined in the striatum of adult male mice following exposure to drinking water containing As, Pb, and/or Cd. We found that exposure to a metal mixture impaired motor coordination. After 4 weeks of treatment, a significant decrease in dopamine content and expression of TH, DAT, and VMAT2 was observed in the striatum of metal-mixture-treated mice, compared to the controls or single-metal-exposed groups. However, DRD1 and DRD2 expression did not significantly change with metal treatment. These results suggest that altered dopaminergic neurotransmission by the collective action of metals may contribute to metal-mixture-induced neurobehavioral disorders.

Section: Discussionmentioning

confidence: 99%

Combined Exposure to Metals in Drinking Water Alters the Dopamine System in Mouse Striatum

Lee

2021

IJERPH

“…In our study, we also found that expressions of RhoA and ROCK were increased in AD mice and xanthoceraside significantly reversed these abnormal expressions. SPAR, a large multimodular scaffold protein in the PSD, combines with a complex of PSD-95 to regulate spine morphogenesis [61]. Snk induces the degradation of SPAR, further leading to spine shrinkage and loss.…”

Section: Discussionmentioning

confidence: 99%

Xanthoceraside prevented synaptic loss and reversed learning-memory deficits in APP/PS1 transgenic mice

et al. 2019

Xanthoceraside, a novel triterpenoid saponin, has been found to attenuate learning and memory impairments in AD animal models. However, whether xanthoceraside has a positive effect on synaptic morphology remains unclear. Herein, we evaluated the effects of xanthoceraside on learning and memory impairments and the abnormalities of synaptic structure in APP/PS1 transgenic mice. The behavioral experiments demonstrated that xanthoceraside attenuated the imaginal memory and spatial learning impairments, and improved social interaction. Transmission electron microscopy and Golgi staining showed that xanthoceraside ameliorated synapse morphology abnormalities and dendritic spine density deficits, respectively. Western-blot analysis identified that xanthoceraside increased the expression of SYP and PSD95, activated BDNF/TrkB/MAPK/ERK and PI3K/Akt signaling pathways, meanwhile decreased the expression of RhoA, ROCK and Snk, increased the levels of SPAR, and activated the BDNF/TrkB/cofilin signaling pathway. Taken together, our study indicated that xanthoceraside improved cognitive function and protected both synaptic morphology and dendritic spine in APP/PS1 transgenic mice, which might be related in part to its activation in the BDNF/TrkB pathway.

“…26 Zhou et al also suggested that co-exposure to Cd, Pb, As and Hg may disrupt synaptic homeostasis and induce neurotoxicity. 27 According to a study on PC-12 cells, Rahman 28 Besides, some studies on the coexposure of Cd and nanoparticles have been reported. According to the research studies of Ahamed et al, silica nanoparticles 29 and TiO 2 nanoparticles 30 increased the bioaccumulation and toxicity of Cd in cells.…”

Section: Introductionmentioning

confidence: 99%

“…26 Zhou et al also suggested that co-exposure to Cd, Pb, As and Hg may disrupt synaptic homeostasis and induce neurotoxicity. 27 According to a study on PC-12 cells, Rahman et al proposed that Zn could suppress Cd-induced oxidative stress and apoptosis. 28 Besides, some studies on the co-exposure of Cd and nanoparticles have been reported.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the effect of nitrate and chloride on Cd(ii)-induced cell oxidative stress by scanning electrochemical microscopy

Pan

Zhang

et al. 2022

Anal. Methods