Post Graduation Program in Biotechnology, Universidade Positivo, Curitiba - PR, Brasil.
Post Graduation Program in Biotechnology, Universidade Positivo, Curitiba - PR, Brasil;
Acta Neurobiol Exp (Wars). 2020;80(2):160-171.
A non‑transgenic 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, risk‑assessment and fear‑related memories. The behavioral tests were followed by brain removal and hippocampal dissection for RNA extraction and qRT‑PCR to assess the expression levels of 4 Alzheimer's disease related genes: Mapt, Apoe, C3 and Ps‑1. 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 (re‑test) 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.
一种基于侧脑室注射链脲佐菌素（STZ）的非转基因大鼠模型已被用作研究与散发性阿尔茨海默病晚期发病机制相关的动物模型，例如解剖和行为损伤。然而，与基因表达相关的分子方面，主要是在海马体中，需要进一步研究。因此，本研究评估了 STZ 给药后的早期和晚期认知功能和海马基因表达。雄性 Wistar 大鼠分为 4 组：STZ（双侧注射）、早期记忆功能评估的对照组（手术后 1 个月=第 1 期，给予相同体积的载体）和晚期记忆功能评估的相同处理组（手术后 4 个月=第 2 期）。通过高架十字迷宫观察动物，以评估与焦虑、风险评估和恐惧相关记忆相关的行为。行为测试后，取出大脑并分离出海马体以提取 RNA 并进行 qRT-PCR 以评估 4 种阿尔茨海默病相关基因的表达水平：Mapt、Apoe、C3 和 Ps-1。两个阶段的动物在开放臂的时间百分比和进入次数都增加了，表明与焦虑相关的风险行为，并且与对照组相比，在中心广场的时间百分比增加，表明与厌恶事件相关的工作记忆损伤。统计分析表明，STZ 组的焦虑、记忆和风险评估反应发生改变。此外，STZ 给药后 1 个月，C3 基因检测显示表达增加。因此，目前的数据表明，与促炎细胞因子（如 C3）的表达相关的神经炎症事件与记忆、焦虑和决策改变有关。
