Kumawat, Kanhaiya Lal and Kaushik, Deepak Kumar and Goswami, Praveen and Basu, Anirban (2014) Acute exposure to lead acetate activates microglia and induces subsequent bystander neuronal death via caspase-3 activation. Neurotoxicology, 41. pp. 143-153.

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Abstract

Lead is one of the major pollutants of environment and is highly toxic to the functioning of central nervous system (CNS). The chronic exposure of this heavy metal is debilitating to the functional behavior of an organism. Studies have shown that acute exposure to Pb can lead to glial activation and secretion of cyto-chemokines in both in vitro and in vivo models. However, the cellular source of secretion of these cyto-chemokines remains to be identified. Microglia are monocytes of the brain, and are primary source of cytokine secretion in the CNS. We hypothesized that microglia exposed to Pb can secrete cyto-chemokines, thereby resulting in subsequent neuronal death. Our studies show that stimulation of BV-2 mouse microglia with 10μМ dose of Pb resulted in up-regulation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) pathways, along with activation of an important transcription factor, nuclear factor-κB (NF-κB). Further, we found that the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and cyclooxygenase-2 (COX-2) pro-inflammatory enzyme were increased in response to Pb exposure. Furthermore, treatment with conditioned media from Pb treated BV-2 cells lead to neuronal death in neuroblastoma cells, which potentially involved the activation of caspase-3 enzyme. In all, the current study brings forth critical involvement of microglial activation in mediating the neurotoxicity associated with lead exposure.

Item Type:	Article
Subjects:	Neurodegenerative Disorders Neuro-Oncological Disorders Neurocognitive Processes Neuronal Development and Regeneration Informatics and Imaging Genetics and Molecular Biology
Depositing User:	Dr. D.D. Lal
Date Deposited:	07 Jul 2017 05:40
Last Modified:	09 Dec 2021 11:53
URI:	http://nbrc.sciencecentral.in/id/eprint/157

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