Abstract:
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-α 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 CaMKIIα 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 STZ 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-α, 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 STZ induced memory impairment and neuronal cell death.
