Abstract
Intracerebroventricular streptozotocin (ICV-STZ) injection is among the best animal models to simulate sporadic Alzheimer’s disease (sAD). Abnormality in brain insulin signaling, neurodegeneration, neuroinflammation, cholinergic damage, mitochondrial dysfunction, genetic abnormality, respiratory problem, oxidative stress, gliosis, sleep disturbances are associated with cognitive abnormalities seen in ICV-STZ injected rats. Available experimental evidence has used varying doses of STZ (<1 to 3mg/kg) and studied its effect for different study durations, ranging from 14-21 (short), 30-42 (mild), 90-105 (moderate) and 250-270 (long) days. These studies indicated that 3mg/kg of body-weight is the optimum dose for inducing sAD in the rodents. However, studies on the pathological process with related the morphological and functional abnormalities reported were illusive. Hence in the present study, we have investigated the morpho-functional changes after 3mg/kg ICV-STZ treatment with a follow-up of two months in 54 male Wistar rats (ethical no. 937/IAEC/PhD-2016). Results exhibited a spatial, episodic and avoidance memory decline and increase in anxiety (p<.05) in icv-stz group progressively with time from 15th day to 60th post-injection. morphometry showed hippocampal atrophy ca1, ca3 layer thinning (p="0.007)" ≤0.01) and loss of neurons (p<0.0001) associated third ventricular enlargement rats versus sham, along-with extracellular amyloid plaque ad congored staining. addition, spine golgi-cox impregnation mossy fiber a reduction density control sham (p<0.0001). finally, immunohistochemistry gsk3ß, pi3k mtcox-1 antigen coronal sections revealed an increase mean intensity gsk3ß decrease brain areas limbic system on day. these findings suggests, progressive dementia anxiety 3mg />kg STZ treated rats, which may be due to hippocampal atrophy, amyloidopathy, ventricular enlargement, synaptic dysfunction and deficits in energy homeostasis of brain.