Dahlqvist P, Rönnbäck A, Risedal A, Nergårdh R, Johansson I-M, Seckl J R, Johansson B B, Olsson T
Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, S-901 85, Umeå, Sweden.
Neuroscience. 2003;119(3):643-52. doi: 10.1016/s0306-4522(03)00195-7.
Housing rats in an enriched environment improves functional outcome after ischemic stroke, this may reflect neuronal plasticity in brain regions outside the lesion. Which components of the enriched environment that are of greatest importance for recovery after brain ischemia is uncertain. We have previously found that enriched environment and social interaction alone both improve functional recovery after focal cerebral ischemia, compared with isolated housing with voluntary wheel-running. In this study, the aim was to separate components of the enriched environment and investigate the effects on some potential mediators of improved functional recovery; such as the inducible transcription factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the glucocorticoid and serotonin systems. After permanent middle cerebral artery occlusion, rats were divided into four groups: individually housed with no equipment (deprived group), individually housed with free access to a running wheel (running group), housed together in a large cage with no equipment (social group) or in a large cage furnished with exchangeable bars, chains and other objects (enriched group). mRNA expression of inducible transcription factors, serotonin and glucocorticoid receptors was determined with in situ hybridisation 1 month after cerebral ischemia. Rats housed in enriched or social environments showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical regions outside the lesion and in the CA1 (cornu ammonis region of the hippocampus), compared with isolated rats with or without a running wheel. NGFI-A and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT(1A)) mRNA expression and binding, as well as 5-HT(2A) receptor mRNA expression were decreased in the hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor gene expression was increased in the dentate gyrus amongst wheel-running rats. No group differences were found in plasma corticosterone levels or mRNA levels of glucocorticoid receptor, corticotropin-releasing hormone, 5-HT(2C) or c-fos. In conclusion, we have found that social interaction is a major component of the enriched environment regarding the effects on NGFI-A and NGFI-B expression. These transcription factors may be important mediators of improved functional recovery after brain infarctions, induced by environmental enrichment.
将大鼠饲养在丰富环境中可改善缺血性中风后的功能结局，这可能反映了损伤灶外脑区的神经元可塑性。丰富环境中对脑缺血后恢复最重要的组成部分尚不确定。我们之前发现，与单独饲养并配备自愿跑步轮相比，丰富环境和社交互动单独都能改善局灶性脑缺血后的功能恢复。在本研究中，目的是分离丰富环境的组成部分，并研究其对功能恢复改善的一些潜在介导因素的影响；如诱导型转录因子神经生长因子诱导基因A（NGFI-A）和NGFI-B，以及糖皮质激素和5-羟色胺系统。在永久性大脑中动脉闭塞后，将大鼠分为四组：单独饲养且无设备（剥夺组）、单独饲养且可自由使用跑步轮（跑步组）、一起饲养在大笼子且无设备（社交组）或饲养在配备可更换横杆、链条和其他物品的大笼子中（丰富组）。脑缺血1个月后，通过原位杂交测定诱导型转录因子、5-羟色胺和糖皮质激素受体的mRNA表达。与有或无跑步轮的单独饲养大鼠相比，饲养在丰富或社交环境中的大鼠在损伤灶外的皮质区域以及CA1（海马的角回区域）中，NGFI-A和NGFI-B的mRNA表达显著更高。皮质和CA1中NGFI-A和NGFI-B的mRNA表达与功能结局显著相关。跑步轮大鼠海马（CA4区域）中的5-羟色胺受体1A（5-HT(1A)）mRNA表达和结合以及5-HT(2A)受体mRNA表达降低。在跑步轮大鼠的齿状回中，盐皮质激素受体基因表达增加。在血浆皮质酮水平或糖皮质激素受体、促肾上腺皮质激素释放激素、5-HT(2C)或c-fos的mRNA水平上未发现组间差异。总之，我们发现就对NGFI-A和NGFI-B表达的影响而言，社交互动是丰富环境的主要组成部分。这些转录因子可能是环境富集诱导脑梗死功能恢复改善的重要介导因素。
