Animal model of Alzheimer's disease induced by streptozotocin: New insights about cholinergic pathway

Alzheimer's disease (AD) is of multifactorial origin, and still presents several gaps regarding its development and progression. Disorders of the cholinergic system are well known to be involved in the pathogenesis of AD, characterized by increased acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and decreased acetyltransferase (ChAT) enzymatic activities. Late onset AD (LOAD) animal model induced by intracerebroventricular injection of streptozotocin (icv-STZ) showed promising results in this context, due to the similarity with the pathophysiology of human LOAD. Thus, this study aimed to assess the long-term effects of icv-STZ on the cholinergic system, through the measuring of AChE and BChE enzymatic activities in hippocampus, prefrontal cortex and liver of animals euthanized 30 and 120-days after the icv-STZ. Regarding the cholinergic response to icv-STZ, the 30-days and 120-days STZ-induced rats exhibit decreased AChE and BChE activities only in the hippocampus. The cognitive deficit was more consistent in the 30-days post icv-STZ animals, as was the weight loss. This is the first study to investigate the long-term effects (more than 60 days) of the icv-STZ on AChE and BChE activities, and our results, as well as those of a recent study, suggest that the cholinergic system may not be compromised by icv-STZ, at least in the long term, which means that this model may not be the best model for studying the cholinergic system in AD or that it is informative only for a short period.