Neurodegeneration, demyelination, and astrogliosis in rat spinal cord by chronic lead treatment

Abstract

Early exposure to lead (Pb) has been associated with an elevated risk of developing neurodegenerative diseases. There is evidence that neuronal damage in chronic Pb exposure can be caused by the convergence of glial damage. Apoptosis may be a possible mechanism of Pb‐induced cell death in the central nervous system. We tested cellular damage and apoptosis in the spinal cord of Wistar rats treated with Pb. Twelve rats were divided into two groups (n = 6): the control group was treated with only drinking water and the other group received 500 ppm of Pb acetate. After 3 months of Pb treatment, all animals were euthanized and spinal cords were extracted. Morphology was evaluated by Nissl and Kluver‐Barrera stainings. Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Specific antibodies were used to evaluate Pb damage in oligodendrocytes, astrocytes, and microglia. A large number of apoptotic bodies was observed in the white matter of the Pb‐treated group. The Pb‐treated group also showed a reduced number of neurons and oligodendrocytes but had an increased number of astrocytes compared with the nontreated group. Our results demonstrate that chronic Pb treatment induces neurodegeneration, demyelination, and astrogliosis in the rat spinal cord.

Combining in vitro assays and mathematical modelling to study developmental neurotoxicity induced by chemical mixtures

“…Lead overload has been associated with the risk of ASD [ 120 ] and it is known to induce both micro- and astro-gliosis in the brain, triggering the production of pro-inflammatory cytokines [ 121 ]. Chronic Lead exposure has been shown to increase the percentage of astrocytes in the spinal cord of rats [ 122 ], and to induce microgliosis and astrogliosis in the hippocampus of young mice via activation of TLR4-MyD88-NFκB signalling pathways [ 123 ]. An increase of GFAP + astrocytes was also demonstrated in NSCs derived from the hippocampus of newborn and adult rats treated with 0−200 μM Lead [ 124 ].…”

Microglia and Astroglia—The Potential Role in Neuroinflammation Induced by Pre- and Neonatal Exposure to Lead (Pb)

“…Furthermore, Li et al, in 2014, showed that early-life Pb exposure significantly affected GFAP expression in the hippocampus of mouse pups [ 69 ]. Additionally, Villa-Cedillo et al, in 2019, demonstrated that chronic Pb treatment induced neurodegeneration, demyelination, and astrogliosis in the rat spinal cord [ 79 ].…”

The Role of TNF-R1-RIPK1/RIPK3 Signaling Pathway in Lead-Induced Necroptosis in the Hippocampus of Mice

“…Moreover, Pb can impact the cholinergic, dopaminergic and glucose metabolism systems, thereby disrupting normal neurotransmission function [22]. Overall, the mechanism of Pb neurotoxicity is multifactorial, including oxidative stress [19], autonomous and orderly cell death [23], autophagy dysregulation [24], epigenetic changes [25], activation of the immune system by microglial and astrocytes [26], and altered calcium-dependent processes [27]. Despite these insights, the precise mechanism of Pb neurotoxicity remains incompletely understood.…”