Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, Florianópolis, Brazil; Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Behav Brain Res. 2019 Sep 16;370:111966. doi: 10.1016/j.bbr.2019.111966. Epub 2019 May 21.
The Spontaneously Hypertensive Rat (SHR) has been proposed as a good model to study the pathways related to neurodegenerative diseases and glucose intolerance. Our research group developed the SLA16 (SHR.LEW-Anxrr16) congenic strain, which is genetically identical to the SHR strain, except for a locus on chromosome 4 (DGR). We applied in silico analysis on DGR to evaluate the association of their genes with neurobiological and metabolic pathways. After, we characterized cholesterol, triglycerides, metabolism of glucose and the behavioral performance of young (2 months old) and adult (8 months old) SHR and SLA16 rats in the open field, object location and water maze tasks. Finally, naïve young rats were repeatedly treated with metformin (200 mg/kg; v.o.) and evaluated in the same tests. Bioinformatics analysis showed that DGR presents genes related to glucose metabolism, oxidative damage and neurodegenerative diseases. Young SLA16 presented higher cholesterol, triglycerides, glucose and locomotion in the open field than SHR rats. In adulthood, SLA16 rats presented high triglycerides and locomotion in the open field and impairment on spatial learning and memory. Finally, the treatment with metformin decreased the glucose tolerance curve and also improved long-term memory in SLA16 rats. These results indicate that DGR presents genes associated with metabolic pathways and neurobiological processes that may produce alterations in glucose metabolism and spatial learning/memory. Therefore, we suggest that SHR and SLA16 strains could be important for the study of genes and subsequent mechanisms that produce metabolic glucose alterations and age-related cognitive deficits.
自发性高血压大鼠(SHR)被提议作为研究与神经退行性疾病和葡萄糖不耐受相关途径的良好模型。我们的研究小组开发了 SLA16(SHR.LEW-Anxrr16)近交系,除了染色体 4 上的一个位点(DGR)外,它在遗传上与 SHR 品系完全相同。我们对 DGR 进行了计算机分析,以评估其基因与神经生物学和代谢途径的关联。之后,我们对年轻(2 个月大)和成年(8 个月大)SHR 和 SLA16 大鼠的胆固醇、甘油三酯、葡萄糖代谢以及在开阔场、物体位置和水迷宫任务中的行为表现进行了特征描述。最后,我们对未接受过处理的年轻大鼠重复给予二甲双胍(200mg/kg;口服)治疗,并在相同的测试中对其进行评估。生物信息学分析表明,DGR 存在与葡萄糖代谢、氧化损伤和神经退行性疾病相关的基因。年轻的 SLA16 大鼠在开阔场中的胆固醇、甘油三酯、葡萄糖和运动能力均高于 SHR 大鼠。在成年期,SLA16 大鼠在开阔场中的甘油三酯和运动能力较高,并且在空间学习和记忆方面存在障碍。最后,二甲双胍的治疗降低了 SLA16 大鼠的葡萄糖耐量曲线,并改善了其长期记忆。这些结果表明,DGR 存在与代谢途径和神经生物学过程相关的基因,这些基因可能导致葡萄糖代谢和空间学习/记忆的改变。因此,我们认为 SHR 和 SLA16 大鼠品系可能对研究导致代谢性葡萄糖改变和与年龄相关的认知缺陷的基因和后续机制非常重要。
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