UGC JOURNAL NUMBER 44557 IJAPRR International Peer Reviewed Refereed Journal, Vol. IV, Issue X, p.n. 18-40, Oct, 2017 Page 18 International Journal of Allied Practice, Research and Review Website: www.ijaprr.com (ISSN 2350-1294) Lead Toxicity Induced Microglial Activation in the Brain Kanhaiya Lal Kumawat 1, 2, # , Praveen Goswami 2, 3, # and A.K. Sharma 2 1. National Brain Research Centre, Manesar, Gurgaon, India-122051 2. Dr. K.N. Modi University, Newai, Rajasthan, India-304021 3. Poddar International College, Jaipur, Rajasthan, India-302020 Abstract - Lead (Pb) shows a considerable amount of heavy metal toxicity in the central nervous system. Neuronal death or neurodegeneration is related to the Pb induced inflammatory processes through microglial activation in brain. Pb induced activation of microglia leads to the expressions of different cytokines, chemokines and enzymes, such as TNF-α, IL-6, MCP-1, Cox-2, caspases, nitric oxide synthetase (NOS 2) etc. leading to trigger different signaling cascades, namely, Extracellular- signal-regulated kinases (ERK1/2), NF-B Pathway, c-jun N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs), p38 MAPK, Akt Pathway in neuroinflammation. Thus, the first line of defense mechanism homeostasis is disturbed by the Pb induced activation of microglia leading to neuronal death. Keywords: Lead(Pb), Microglia, Brain, Neuroinflammation, Central Nervous System (CNS) and Neurotoxicity 1. INTRODUCTION Lead (Pb) is a toxic environmental agent that has debilitating effects on human health. It is considered as the 2 nd most toxic substance according to ATSDR that is being used extensively due to its efficient properties of corrosion resistance and high malleability. Over the years it has been observed that several natural and anthropogenic activities have been the reason for lead contamination in the environment. Lead can come in the atmosphere by efflux from mining lead and other metals, and from industrial units that make or use lead, lead alloys, or lead compounds. Lead in the soil is mainly due to the weathering of lead based paints from the heavy structures like bridges and buildings that stick firmly to the soil particle and settles in the upper layer of the soil. Lead used in gasoline and unleaded petrol and released by the automobiles contributes to lead in air. These soil particles when enters the water bodies do contaminate them too. They may also contaminate the water by getting released from the leaded pipes when the water becomes acidic. Surface water lead contamination is also due to lead containing dust from the environment and industrial effluents of iron and steel industries along with urban run-off. Global lead toxicity – resulting from human activities is responsible to the great increased circulation of lead in soil, water and air – remains significant. Despite a century of cumulative evidence about its threat to the health of children, lead remains to be added to paints, pigments, toys, traditional medications and other