The mechanism underlying streptozotocin injection for the development of a nontransgenic Alzheimer's disease animal model

Abstract

Streptozotocin (STZ) is a widely used chemical agent in biomedical research. It is primarily known for its ability to induce high blood glucose levels in animal models by selectively destroying pancreatic beta cells. Nonetheless, many studies have also used STZ to generate animal models of diabetic complications, such as Alzheimer's disease (AD) animal models. STZ induction promotes hyperglycemia, which activates numerous mechanism pathways that result in the production of pathogenic AD characteristics, including beta-amyloid accumulation and neurofibrillary tangles. Numerous theories exist to elucidate the mechanisms underlying diabetes and AD; however, studies on the potential of an animal model of STZ-induced AD remain limited. Thus, this review summarizes the pathogenesis associated with STZ exposure, particularly in AD animal model studies related to diabetes. More specifically, this study will discuss the relationship between increased blood glucose levels after STZ injection and the process of beta-amyloid formation and insulin dysfunction in the brain.

Keywords: Beta-amyloid; Brain; Hyperglycemia; Neuron; Tau protein.

Fig. 1.. Streptozotocin pathomechanism in pancreatic beta cells. The DNA methylating activity of the methylnitrosourea moiety of STZ, particularly at the O6 position of guanine, causes DNA damage and necrosis in pancreatic beta cells. When the DNA of the cell is damaged, PARP-1 is activated, which causes a decrease in ATP and NAD+, resulting in the formation of free radicals and damaging pancreatic cells. NO, which is generated following the metabolism of STZ, is another potential pathway that has also been linked to cell death.

Fig. 2.. Summary of the impact of hyperglycemia after STZ injection in the animal brain. Hyperglycemia can affect macrophages and microglia as part of the innate immune system, increasing oxidative stress and inflammation, promoting amyloidogenic APP processing, and interrupting insulin receptors, causing insulin dysfunction.