Monnot C, Kalomoiri M, MacNicol E, Kim E, Mesquita M, Damberg P, Van Kampen J M, Kay D G, Turkheimer F, Robertson H A, Cash D, Svenningsson P
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Department of Neuroimaging, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK.
Exp Neurol. 2025 Mar;385:115118. doi: 10.1016/j.expneurol.2024.115118. Epub 2024 Dec 21.
The β-sitosterol-β-ᴅ-glucoside (BSSG) rat model of experimental parkinsonism develops pathological behaviour and motor changes that progress over time. The purpose of this study was to identify early changes in structure and function of the brain of rats treated with BSSG using both structural and resting-state functional MRI. BSSG and non-BSSG rats were fed five days a week for sixteen weeks, then underwent in vivo MRI scans and an assessment of motor performance 2 and 8 weeks later (18 and week 24 from BSSG). Groups of rats were killed at weeks 19 and 25, then imaged again with MR ex vivo, and immunostained for tyrosine hydroxylase (TH). Since BSSG may interfere with cholesterol metabolism in astrocytes, we also studied potential target engagement and measured levels of astrocyte markers GFAP and S100b. At both studied timepoints, functional connectivity (FC) between brain areas with intermediate connectivity was decreased, but brain volumes increased in the BSSG-treated rats. At week 18/19, fine movements were normal, whereas TH and GFAP were decreased in the striatum, but not in the substantia nigra. At week 24/25, fine movements were impaired, and TH was decreased both in the striatum and the substantia nigra and S100b was increased in the substantia nigra. Astrogliosis may contribute to the increased brain volume found after BSSG exposure. Using the BSSG model of parkinsonism, the results demonstrate early functional and structural alterations in MRI imaging that occur before the appearance of detectable motor symptoms.
β-谷甾醇-β-D-葡萄糖苷（BSSG）诱导的实验性帕金森病大鼠模型会随着时间推移出现病理行为和运动变化。本研究的目的是使用结构和静息态功能磁共振成像（MRI）来识别接受BSSG治疗的大鼠大脑结构和功能的早期变化。BSSG组和非BSSG组大鼠每周喂食5天，持续16周，然后在2周和8周后（即BSSG处理后的第18周和第24周）进行活体MRI扫描和运动性能评估。在第19周和第25周处死大鼠组，然后进行离体MR成像，并对酪氨酸羟化酶（TH）进行免疫染色。由于BSSG可能会干扰星形胶质细胞中的胆固醇代谢，我们还研究了潜在的靶点结合情况，并测量了星形胶质细胞标志物胶质纤维酸性蛋白（GFAP）和S100b的水平。在两个研究时间点，中等连接性脑区之间的功能连接性（FC）均降低，但BSSG处理的大鼠脑体积增加。在第18/19周，精细运动正常，而纹状体中的TH和GFAP减少，但黑质中未减少。在第24/25周，精细运动受损，纹状体和黑质中的TH均减少，黑质中的S100b增加。星形胶质细胞增生可能导致BSSG暴露后发现的脑体积增加。使用帕金森病的BSSG模型，结果表明在可检测到的运动症状出现之前，MRI成像中就已经出现了早期功能和结构改变。
