Piazza Francele Valente, Segabinazi Ethiane, Centenaro Lígia Aline, do Nascimento Patrícia Severo, Achaval Matilde, Marcuzzo Simone
Programa de Pós-Graduação em Neurociências, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite 500, CEP: 90050-170, Porto Alegre, RS, Brazil.
Metab Brain Dis. 2014 Mar;29(1):93-104. doi: 10.1007/s11011-013-9467-2. Epub 2013 Dec 10.
Type 1 diabetes mellitus (T1DM) has been associated with long-term complications in the central nervous system, causing brain cellular dysfunctions and cognitive deficits. On the other hand, enriched environment (EE) induces experience-dependent plasticity, especially in the hippocampus, improving the performance of animals in learning and memory tasks. Thus, our objective was to investigate the influence of the EE on memory deficits, locomotion, corticosterone levels, synaptophysin (SYP) protein immunoreactivity, cell survival and microglial activation in the dentate gyrus (DG) of T1DM rat hippocampus. Male Wistar rats (21-day-old) were exposed to EE or maintained in standard housing (controls, C) for 3 months. At adulthood, the C and EE animals were randomly divided and diabetes was induced in half of them. All the animals received 4 doses of BrdU, 24 h apart. Hippocampus-dependent spatial memory, general locomotion and serum corticosterone levels were evaluated at the end of the experiment. The animals were transcardially perfused 30 days post-BrdU administration. Our results showed that EE was able to prevent/delay the development of memory deficits caused by diabetes in rats, however it did not revert the motor impairment observed in the diabetic group. SYP immunoreactivity was increased in the enriched healthy group. The EE decreased the serum corticosterone levels in diabetic adult rats and attenuated the injurious microglial activation, though without altering the decrease of the survival cell. Thus, EE was shown to help to ameliorate cognitive comorbidities associated with T1DM, possibly by reducing hyperactivity in the hypothalamic-pituitary-adrenal axis and microglial activation in diabetic animals.
1型糖尿病（T1DM）与中枢神经系统的长期并发症相关，可导致脑细胞功能障碍和认知缺陷。另一方面，丰富环境（EE）可诱导经验依赖性可塑性，尤其是在海马体中，可改善动物在学习和记忆任务中的表现。因此，我们的目的是研究EE对T1DM大鼠海马齿状回（DG）中记忆缺陷、运动、皮质酮水平、突触素（SYP）蛋白免疫反应性、细胞存活和小胶质细胞激活的影响。雄性Wistar大鼠（21日龄）暴露于EE或饲养在标准环境中（对照组，C）3个月。成年后，将C组和EE组动物随机分组，其中一半诱导糖尿病。所有动物每隔24小时接受4剂溴脱氧尿苷（BrdU）。在实验结束时评估海马体依赖性空间记忆、一般运动和血清皮质酮水平。在给予BrdU后30天对动物进行心脏灌注。我们的结果表明，EE能够预防/延缓大鼠糖尿病引起的记忆缺陷的发展，然而它并未恢复糖尿病组中观察到的运动障碍。在丰富环境健康组中，SYP免疫反应性增加。EE降低了成年糖尿病大鼠的血清皮质酮水平，并减弱了有害的小胶质细胞激活，尽管没有改变存活细胞的减少。因此，EE显示有助于改善与T1DM相关的认知合并症，可能是通过降低糖尿病动物下丘脑-垂体-肾上腺轴的活动亢进和小胶质细胞激活来实现的。
