PMID- 24530660
OWN - NLM
STAT- MEDLINE
DCOM- 20141114
LR  - 20140328
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 41
DP  - 2014 Mar
TI  - Acute exposure to lead acetate activates microglia and induces subsequent 
      bystander neuronal death via caspase-3 activation.
PG  - 143-53
LID - S0161-813X(14)00025-4 [pii]
LID - 10.1016/j.neuro.2014.02.002 [doi]
AB  - 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 10mucapital EM, Cyrillic 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-kappaB (NF-kappaB). 
      Further, we found that the levels of tumor necrosis factor-alpha (TNF-alpha), 
      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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Kumawat, Kanhaiya Lal
AU  - Kumawat KL
AD  - National Brain Research Centre, Manesar, Haryana 122051, India; Dr. K.N. Modi 
      University, Newai, Rajasthan 304021, India. Electronic address: 
      kanhaiya81@gmail.com.
FAU - Kaushik, Deepak Kumar
AU  - Kaushik DK
AD  - National Brain Research Centre, Manesar, Haryana 122051, India. Electronic 
      address: deepakkaushiik@gmail.com.
FAU - Goswami, Praveen
AU  - Goswami P
AD  - Dr. K.N. Modi University, Newai, Rajasthan 304021, India; Poddar International 
      College, Jaipur 302020, India. Electronic address: drpraveen.goswami@gmail.com.
FAU - Basu, Anirban
AU  - Basu A
AD  - National Brain Research Centre, Manesar, Haryana 122051, India. Electronic 
      address: anirban@nbrc.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140214
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Cytokines)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 5)
RN  - EC 3.4.22.- (Caspase 3)
RN  - RX077P88RY (lead acetate)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Caspase 3/metabolism
MH  - Cell Death/drug effects
MH  - Cell Line, Transformed
MH  - Cell Survival/drug effects
MH  - Culture Media, Conditioned/pharmacology
MH  - Cyclooxygenase 2/metabolism
MH  - Cytokines/metabolism
MH  - Dose-Response Relationship, Drug
MH  - MAP Kinase Kinase Kinase 5/metabolism
MH  - Mice
MH  - Microglia/*drug effects
MH  - Molecular Weight
MH  - Neurons/*physiology
MH  - Organometallic Compounds/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Time Factors
OTO - NOTNLM
OT  - Apoptosis
OT  - COX-2
OT  - Central nervous system
OT  - Lead
OT  - Microglia
OT  - NF-kappaB
EDAT- 2014/02/18 06:00
MHDA- 2014/11/15 06:00
CRDT- 2014/02/18 06:00
PHST- 2013/08/16 00:00 [received]
PHST- 2014/01/20 00:00 [revised]
PHST- 2014/02/04 00:00 [accepted]
PHST- 2014/02/18 06:00 [entrez]
PHST- 2014/02/18 06:00 [pubmed]
PHST- 2014/11/15 06:00 [medline]
AID - S0161-813X(14)00025-4 [pii]
AID - 10.1016/j.neuro.2014.02.002 [doi]
PST - ppublish
SO  - Neurotoxicology. 2014 Mar;41:143-53. doi: 10.1016/j.neuro.2014.02.002. Epub 2014 
      Feb 14.