Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 117, Issue -, Pages 104-117Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2013.11.035
Keywords
Streptozotocin; Memory impairment; Free radicals; Glial activation; Synaptic markers
Funding
- Council for Scientific and Industrial Research (CSIR)
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In the present study the role of glial activation and post synaptic toxicity in ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment set up 1: Memory deficit was found in Morris water maze test on 14-16 days after STZ (ICV; 3 mg/Kg) administration. STZ causes increased expression of GFAP, CD11b and TNF-alpha indicating glial activation and neuroinflammation. STZ also significantly increased the level of ROS, nitrite, Ca2+ and reduced the mitochondrial activity in synaptosomal preparation illustrating free radical generation and excitotoxicity. Increased expression and activity of Caspase-3 was also observed in STZ treated rat which specify apoptotic cell death in hippocampus and cortex. STZ treatment showed decrease expression of post 'synaptic markers CaMKII alpha and PSD-95, while, expression of pre synaptic markers (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic neurotoxicity. Oral treatment with Memantine (10 mg/kg) and Ibuprofen (50 mg/kg) daily for 13 days attenuated Sri induced glial activation, apoptotic cell death and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2: where memory function was not affected i.e. 7-9 days after STZ treatment. The level of GFAP, CD11b, TNF-alpha, ROS and nitrite levels were increased. On the other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca2+ levels remained unaffected. Collective data indicates that neuroinflammatory process and oxidative stress occurs earlier to apoptosis and does not affect memory function. Present study clearly suggests that glial activation and post synaptic neurotoxicity are the key factors in Sri induced memory impairment and neuronal cell death. (C) 2013 Elsevier Inc. All rights reserved.
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