Department of Radiology, Tongji Hospital, Medical School of Tongji University, No. 389, Xincun Road, Putuo District, Shanghai, 200065, China.
J Mol Neurosci. 2013 Jul;50(3):434-42. doi: 10.1007/s12031-013-9951-5. Epub 2013 Jan 15.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular accumulation of amyloid deposits. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor whose levels have been shown to be decreased in AD brains. BDNF supplementation can offer improvement in the course of AD. However, the means of assessment are still relatively limited. In the present study, 1H-MRS was used to evaluate the therapeutic effects of bilateral intraventricular BDNF infusion into Alzheimer's disease APP/PS1 double transgenic mice. For comparison to the 1H-MRS observations, Fluoro-Jade B staining and immunofluorescence for beta amyloid peptides (Aβ), glial fibrillary acidic protein, and tropomyosin-related kinase B (TrkB) were also performed. Our results showed that N-acetylaspartate (NAA) levels increased and myoinositol levels decreased in the BDNF group compared with the PBS group. However, the BDNF group NAA level was still lower than the control group at 6 weeks after infusion. These changes correlated with increased immunoreactivity for TrkB, decreased compact Aβ peptide containing plaques, and decreased Fluoro-Jade B-positive cells in the BDNF-infused mice compared to vehicle controls. These findings demonstrate that 1H-MRS may be a promising means of evaluating the therapeutic effects of BDNF on AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是细胞外淀粉样沉积的积累。脑源性神经营养因子（BDNF）是一种神经营养因子，其水平已被证明在 AD 大脑中降低。BDNF 补充可以改善 AD 的病程。然而，评估手段仍然相对有限。在本研究中，使用 1H-MRS 评估了将 BDNF 双侧脑室输注到阿尔茨海默病 APP/PS1 双转基因小鼠中的治疗效果。为了与 1H-MRS 观察结果进行比较，还进行了 Fluoro-Jade B 染色和β淀粉样肽（Aβ）、神经胶质纤维酸性蛋白和原肌球蛋白相关激酶 B（TrkB）的免疫荧光染色。我们的结果表明，与 PBS 组相比，BDNF 组的 N-乙酰天冬氨酸（NAA）水平升高，肌醇水平降低。然而，与对照组相比，输注后 6 周时 BDNF 组的 NAA 水平仍然较低。这些变化与 BDNF 输注小鼠中 TrkB 的免疫反应性增加、致密 Aβ肽含量减少以及 Fluoro-Jade B 阳性细胞减少相关。这些发现表明，1H-MRS 可能是评估 BDNF 对 AD 治疗效果的一种很有前途的方法。
