Intracerebroventricular streptozotocin induces behavioral impairments and increases short­term C3 gene expression in the hippocampus of Wistar rats.

A non­transgenic rat model based on intracerebroventricular injection of streptozotocin (STZ) has been used as an animal model to investigate mechanisms associated to the late onset of sporadic Alzheimer's disease, such as anatomical and behavioral impairments. However, molecular aspects related to gene expression, mainly in the hippocampus, require more investigation. Thus, this study evaluated the early and late cognitive functions and hippocampal gene expression after STZ administration. Male Wistar rats were divided into 4 groups: STZ (injected bilaterally), control group for the early memory function evaluation (1 month after surgery = phase 1, same volume of vehicle), and the same treatment for the late memory function evaluation (4 months after surgery = phase 2). The animals were observed in the elevated plus maze to assess behaviors related to anxiety, risk­assessment and fear­related memories. The behavioral tests were followed by brain removal and hippocampal dissection for RNA extraction and qRT­PCR to assess the expression levels of 4 Alzheimer's disease related genes: Mapt, Apoe, C3 and Ps­1. Animals from both phases showed increased time percentage and number of entries into the open arms, indicating risk behavior associated with anxiety, and an increased time percentage in the center square for both exposures (re­test) when compared to the control group, suggesting working memory impairment related to an aversive event. Statistical analyses indicated that the STZ group presented alterations in anxiety, memory and risk assessment responses. Additionally, one month after STZ administration, C3 gene assays revealed an increased expression. Therefore, current data indicate that neuroinflammatory events linked to the expression of pro inflammatory cytokines such as C3 are related to memory, anxiety and decision-making alterations.