Study of lead-induced neurotoxicity in cholinergic cells differentiated from bone marrow-derived mesenchymal stem cells

Abstract

The developing brain is susceptible to the neurotoxic effects of lead. Exposure to lead has main effects on the cholinergic system and causes reduction of cholinergic neuron function during brain development. Disruption of the cholinergic system by chemicals, which play important roles during brain development, causes of neurodevelopmental toxicity. Differentiation of stem cells to neural cells is recently considered a promising tool for neurodevelopmental toxicity studies. This study evaluated the toxicity of lead acetate exposure during the differentiation of bone marrow–derived mesenchyme stem cells (bone marrow stem cells, BMSCs) to cholinergic neurons. Following institutional animal care review board approval, BMSCs were obtained from adult rats. The differentiating protocol included two stages that were pre-induction with β-mercaptoethanol (BME) for 24 h and differentiation to cholinergic neurons with nerve growth factor (NGF) over 5 days. The cells were exposed to different lead acetate concentrations (0.1–100 μm) during three stages, including undifferentiated, pre-induction, and neuronal differentiation stages; cell viability was measured by MTT assay. Lead exposure (0.01–100 μg/ml) had no cytotoxic effect on BMSCs but could significantly reduce cell viability at 50 and 100 μm concentrations during pre-induction and neuronal differentiation stages. MAP2 and choline acetyltransferase (ChAT) protein expression were investigated by immunocytochemistry. Although cells treated with 100 μm lead concentration expressed MAP2 protein in the differentiation stages, they had no neuronal cell morphology. The ChAT expression was negative in cells treated with lead. The present study showed that differentiated neuronal BMSCs are sensitive to lead toxicity during differentiation, and it is suggested that these cells be used to study neurodevelopmental toxicity.

Effect of the Sublethal Dose of Lead Acetate on Malondialdehyde, Dopamine, and Neuroglobin Concentrations in Rats

“…The current results are in agreement with those reported by Abdel-Wahab and Metwally (2014), Velaga et al (2014), andSutaria et al (2022). Lead-induced neurotoxicity has been linked to oxidative stress, caused by the disruption of the antioxidant balance in cells (Jafarzadeh et al, 2022), dysregulation of cell signaling, and altered neurotransmission (Li et al, 2016).…”

Temperature- and chemical-induced neurotoxicity in zebrafish

“…Increases in Ach levels were also observed in zebrafish larvae following exposure to hexabromobenzene and pentabromobenzene ( Chen et al, 2021 ). The interference with AchE is a significant pathway through which chemical substances induce neurotoxicity ( Reddy et al, 2007 ; Jafarzadeh et al, 2022 ). For instance, exposure to fluoxetine or a combination of microcystin-LR and nitrite significantly decreased AchE expression and activity in zebrafish brain ( Yang et al, 2022 ; Orozco-Hernandez et al, 2022 ).…”