Department of Pharmacy, School of Medical and Pharmaceutical Sciences, University of Genoa, Viale Cembrano 4, 16148, Genoa, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, Italy.
Neuropharmacology. 2019 Feb;145(Pt A):75-86. doi: 10.1016/j.neuropharm.2018.01.026. Epub 2018 Feb 2.
The effect of "prophylactic" environmental stimulation on clinical symptoms and presynaptic defects in mice suffering from the experimental autoimmune encephalomyelitis (EAE) at the acute stage of disease (21 ± 1 days post immunization, d.p.i.) was investigated. In EAE mice raised in an enriched environment (EE), the clinical score was reduced when compared to EAE mice raised in standard environment (SE).Concomitantly, gain of weight and increased spontaneous motor activity and curiosity were observed, suggesting increased well-being in mice. Impaired glutamate exocytosis and cyclic adenosine monophosphate (cAMP) production in cortical terminals of SE-EAE mice were evident at 21 ± 1 d.p.i.. Differently, the 12 mM KCl-evoked glutamate exocytosis from cortical synaptosomes of EE-EAE mice was comparable to that observed in SE and EE-control mice, but significantly higher than that in SE-EAE mice. Similarly, the 12 mM KCl-evoked cAMP production in EE-EAE mice cortical synaptosomes recovered to the level observed in SE and EE-control mice. MUNC-18 and SNAP25 contents, but not Syntaxin-1a and Synaptotagmin 1 levels, were increased in cortical synaptosomes from EE-EAE mice when compared to SE-EAE mice. Circulating IL-1β was increased in the spinal cord, but not in the cortex, of SE-EAE mice, and it did not recover in EE-EAE mice. Inflammatory infiltrates were reduced in the cortex but not in the spinal cord of EE-EAE mice. Demyelination was observed in the spinal cord; EE significantly diminished it. We conclude that "prophylactic" EE is beneficial to synaptic derangements and preserves glutamate transmission in the cortex of EAE mice. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".
在实验性自身免疫性脑脊髓炎(EAE)疾病的急性阶段(免疫后 21±1 天,d.p.i.),研究了“预防性”环境刺激对患有 EAE 的小鼠临床症状和突触前缺陷的影响。与在标准环境(SE)中饲养的 EAE 小鼠相比,在丰富环境(EE)中饲养的 EAE 小鼠的临床评分降低。同时,观察到体重增加、自发运动活动和好奇心增加,表明小鼠的幸福感增加。在 SE-EAE 小鼠的皮质末端,21±1 d.p.i.时明显存在谷氨酸外排和环磷酸腺苷(cAMP)生成受损。相反,EE-EAE 小鼠皮质突触小体中 12mM KCl 诱发的谷氨酸外排与 SE 和 EE 对照小鼠观察到的水平相当,但明显高于 SE-EAE 小鼠。同样,EE-EAE 小鼠皮质突触小体中 12mM KCl 诱发的 cAMP 生成恢复到 SE 和 EE 对照小鼠观察到的水平。与 SE-EAE 小鼠相比,EE-EAE 小鼠皮质突触小体中的 MUNC-18 和 SNAP25 含量增加,但 Syntaxin-1a 和 Synaptotagmin 1 水平没有增加。SE-EAE 小鼠脊髓中循环的 IL-1β 增加,但在皮质中没有增加,而在 EE-EAE 小鼠中没有恢复。EE-EAE 小鼠皮质中的炎症浸润减少,但脊髓中没有。EE 显著减少了 EAE 小鼠脊髓中的脱髓鞘。我们得出结论,“预防性”EE 有利于突触紊乱,并在 EAE 小鼠的皮质中保存谷氨酸传递。本文是特刊“环境富集的神经生物学”的一部分。