Download AB097PSI-AOAPO_KalyaniChaubey_30092016

Molecular mechanism reveal that sarin exposure leads to CNS injury in Rats
Kalyani Chaubey1*, SI Alam2, DP Nagar3, CK Waghmare1, SC Pant3, Lokendra Singh4, Nalini Srivastava5
and BK Bhattacharya1
1
Biochemistry Division 2Biotechnology Division 3Pharmacology and Toxicology Division
4
Director Defence Research & Development Establishment (DRDE), 5Jiwaji University,
Gwalior (MP)- 474002, India.
[email protected]
Sarin is an organophosphorus compound which irreversibly inhibits acetylcholine esterase
(AChE). Acute effects of exposure include lacrimation, salivation, tremors, bulging of eye balls,
paralysis, while the chronic effect causes neurological and neurobehavioral abnormalities. In
this study, proteomic changes after a single 0.5 LD50 dose of sarin exposure was performed to
investigate some milestone changes related to long term CNS injury. Altogether, this study
established the major molecular mechanism associated with toxic insult.
Plasma and brain choline esterase activities were estimated to determine AChE inhibition. We
used 2DE- MS approach to identify the differentially expressed proteins, which was further
characterized by western blot and immunohistochemistry. Results were further validated by
histology.
The results revealed that most of the proteins related to chaperone, cytoskeleton function,
energy and carbohydrate metabolism as well as signal transduction pathways had altered
expression levels. Moreover, by interactome predictions, we observed Parkinson’s disease
related proteins showed at the top, with least false discovery rate. Thus we tried to trace out
major mechanisms associated with sarin exposure and observed mitochondrial dysfunction, ER
stress and defect in synaptic plasticity just after post sarin exposure. For long term changes,
defects in protein folding and the accumulation of some protein related to neurodegenerative
diseases were observed. Long term sarin exposure was related to defects in cognitive function
and it caused astrosytes gliosis, activation of microglia which leads to neurodegenerative
condition.
This is the first proteomic study of surviving animals (Wistar rats) after sarin exposure. The
significant findings of this work will serve as an initial framework which will give greater insight in
the major mechanisms associated with toxin exposure leading to CNS injury. Therefore, this
study opens new avenues for elucidation of therapeutic targets after sarin exposure.
Poster presentation- Disease Proteomics in Plant, Animal and Human Health