Журнал болезни Альцгеймера и паркинсонизма

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Comparative Analysis of Intrahippocampal Amyloid Beta (1-42) and Intracerbroventricular Streptozotocin Models of Alzheimer's Disease: Possible Behavioral, Biochemical, Mitochondrial, Cellu lar and Histopathological Evidences

Arti Singh and Anil Kumar

Background: Alzheimer’s disease (AD), one of the most common progressive neurodegenerative disorders that leads to dementia in aged humans. Amyloid beta [Aβ (1-42)] model has an ability to mimic many pathological aspects of human AD. Intracerebroventricular streptozotocin (icv-STZ) is an another relevant model for sporadic dementia of Alzheimer’s type. However, both the models are frequently used to AD in experimental animals.

Objective: Aim of the present study was to compare these two animal models of AD in order to comment on the best and reliable model of AD as well as screening of the neuroprotectants.

Materials and Methods: Animals received a single bilateral intrahippocampal (ih) injection of Aβ (1-42) (1 μg/μl; 4 μl/site) and single bilateral icv injection of STZ (3 mg/kg; 4 μl/site). Galantamine (2 mg/kg) was used as a standard drug and administered for a period of 21 days. Various neurobehavioral parameters were evaluated, followed by biochemical (oxidative stress parameters), molecular (TNF-α level), mitochondrial respiratory enzyme complexes (Complex I, II, III, IV) and histopathological (H&E staining) parameters.

Results: In the present study, ih-Aβ (1-42) administration significantly impaired cognitive performance on MWM test, increased oxidative stress markers (raised lipid peroxidation, nitrite concentration, reduced glutathione, catalase activity), increased AChE level and neuroinflammation (increased TNF-α levels), reduced mitochondrial respiratory enzyme complexes (complex I,II,III,IV) and histopathological alterations as compared to single bilateral icv-STZ administration. The effect of galantamine (2 mg/kg) was significantly produced its protective effect in reversing these neurobehavioral, biochemical, cellular and histopathological parameters as compared to their respective controls [ih-Aβ (1-42) and icv-STZ]

Conclusions: Result of the present study suggests that the single bilateral ih-Aβ (1-42) model is the most effective and reliable model of AD as compared to single bilateral icv-STZ.