Cadmium induces actin cytoskeleton alterations and dysfunction in Neuro‐2a cells

Abstract

Cadmium (Cd) is considered a possible etiological factor in neurodegenerative diseases. However, the exact mechanism by which Cd induces neurotoxicity is not well elucidated. In this study, Neuro-2a cells were treated with 0, 10, 20, and 40 μM cadmium chloride for 24 hours to investigate the effects of Cd on the cytoskeleton of nerve cells. MTT assay and ELISA assay were used to examine cell viability and release of lactate dehydrogenase (LDH) from cells, respectively. Results showed that Cd reduced cell viability and increased the release of LDH in a dose-dependent manner (P < 0.05). The morphology of treated cell was damaged as indicated by cell collapse and dimensionality reduction. Moreover, the axonal spines and normal features of Cd-treated neurons disappeared. We checked the ultrastructure of Neuro-2a cells and found that Cd-induced swelling, membrane damage, overflow of cytoplasm contents, and cell fragmentation. Damaged mitochondria, expanded endoplasmic reticulum, and abnormal microfilaments were found in Cd-treated cells rather than in untreated cells. Compared with the control group, the relative release of glutamate in the supernatant after Cd treatment was reduced, indicating that Cd exposure could reduce the release of glutamate by inhibiting the function of nerve-2a cells. Cd decreased the mRNA and protein expression levels of cytoskeletal proteins including DBN, SYP, and TAU, which might promote cytoskeleton alterations in Cd-treated cells. In conclusion, Cd-induced actin cytoskeleton alterations and dysfunction of cultured neurons. The results of the present study provide new insights for the investigation of Cd-induced neurotoxicity.

Cell organelles as targets of mammalian cadmium toxicity

“…Swollen rough ER has been reported for chromium (Cr 6+ ; K 2 Cr 2 O 7 ) (Venter et al 2017) suggesting that toxic metals can affect ER structure but no evidence for ultrastructural ER changes for cadmium have been observed in electron microscopy studies of liver and kidney rat tissue (Asar et al 2004;Venter et al 2017). In contrast, swollen, disorganized and damaged rough ER by cadmium was observed in insect cells (66 µM CdCl 2 , 24 h) (Braeckman et al 1999), neuroblastoma cells (20-40 µM CdCl 2 , 24 h) (Ge et al 2019) and rat liver (0.84 mg/kg, i.p. CdAc, 48-96 h) (Early et al 1992).…”

“…Though it is not a focus of this review, it is essential to note the effects of cadmium on cytoskeletal proteins, on which trafficking vesicles and organelles travel around the cell interior. Since the cell's cytoskeleton, such as actin filaments, is regulated by calcium (Izadi et al 2018), it is clear to see how cadmium affects the formation of filamentous actin (Liu et al 2018b;Templeton and Liu 2013) and decreases expression of tau, DBN-1 and α-synuclein cytoskeletol proteins (Ge et al 2019). Disruption of these protein tracks will undoubtedly affect organelle communications, vesicular mobility, and downstream signaling (Moujaber and Stochaj 2020).…”

Bisphenol-A Exposure Induced Neurotoxicity and Synapse and Cytoskeleton Dysfunction in Neuro-2a Cells

“…Cell viability was measured using CCK-8 assay as described (Ge et al 2019). In brief, Neuro-2a cells were seeded at a density of 2 × 10 4 cells/well in 96-well plates and treated with 0 (MEM), DMSO, and 150 μM BPA at the designated time points.…”

“…The results of the present study showed that the expression of Dbn decreased with prolonged treatment time. Similarly, cadmium inhibited the mRNA and protein expression levels of Dbn in Neuro-2a cells(Ge et al 2019).…”

Molecular Mechanisms of Environmental Metal Neurotoxicity: A Focus on the Interactions of Metals with Synapse Structure and Function

“…CdCl 2 induces the disassembly of the cytoskeleton in a variety of cultured neuronal cells, targeting both the actin [ 127 ], and the microtubules [ 128 ] networks. Cd induces the destruction of microtubules and decreases acetylated tubulin levels in primary rat cortical neurons [ 129 ].…”