A new treatment regime for sodium azide to evoke experimental Alzheimer's disease for pharmacological screening

Alzheimer's disease (AD) is characterized by a progressive decline of cognitive functions. Comparative studies identified that there are no detectable signs of drug-induced changes in cognitive functions in healthy animals brain versus diseased brain, therefore, to see decreased behavioral manner of AD suffered animals needs to mimic all specific features of the disease [1]. More evidence suggests the early role of reactive oxygene species in AD major source of which is the mitochondria [2]. The mitochondrial poisoning hypothesis of AD underlying is based on the fact that in human post-mortem AD brains the complex IV activity declines [3]. Inhibition of this complex could be evoked by chronic subcutaneous sodium azide (NaN3) treatment via implanted osmotic minipumps in animals [4]. For screening, however, minipumps are not ideal tools due to high cost, one-time usability and long treatment time. We developed a new method to produce AD–like dementia by selective inhibition of cytochrome C complex using intraperitoneally (ip.) injected NaN3 in various doses (10–15 mg/kg/day) in rats. We explored the dose-effect relationships of the ip. applied mitochondrial poison and established a complex test system to study alterations of the cognitive functions caused by NaN3 treatment. Furthermore, we found the optimal dose and treatment regime of NaN3 to evoke histopathological changes in treated animals.