Weng Jun-Cheng, Tikhonova Maria A, Chen Jian-Horng, Shen Mei-Shiuan, Meng Wan-Yun, Chang Yen-Ting, Chen Ke-Hsin, Liang Keng-Chen, Hung Ching-Sui, Amstislavskaya Tamara G, Ho Ying-Jui
Department of Medical Imaging and Radiological Sciences, Department of Medical Imaging, Chung Shan Medical University Hospital, Chung Shan Medical University, Taichung 402, Taiwan, ROC.
Laboratory of Experimental Models of Neurodegenerative Processes, Federal State Budgetary Scientific Institution "Scientific Research Institute of Physiology and Basic Medicine", Novosibirsk 630117, Russia.
Behav Brain Res. 2016 May 15;305:126-39. doi: 10.1016/j.bbr.2016.02.034. Epub 2016 Mar 3.
Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD.
锰增强磁共振成像（MEMRI）是一种广泛应用于检测活体动物大脑神经元活动的技术。头孢曲松（CEF）已被证明在神经退行性疾病中具有神经保护作用。本研究旨在阐明，在1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的帕金森病（PD）大鼠模型中，已知的CEF诱导的神经元保护作用是否伴随着神经发生以及神经元活动丧失的减少。在MPTP损伤后（第0天），大鼠接受CEF（100mg/kg/天，腹腔注射）或生理盐水治疗15天。然后在第13天给它们注射氯化锰（40mg/kg，腹腔注射），并在第14天进行脑部MRI扫描，随后在第15天取脑进行组织学评估。结果表明，MPTP损伤导致黑质纹状体多巴胺能（DAergic）系统以及海马CA1、CA3和齿状回（DG）区域的神经元活动和密度降低，DG区神经发生减少，但丘脑底核（STN）活动亢进。CEF治疗可预防这些神经元变化。证实了MEMRI的R1值与海马神经元密度之间存在正相关。海马和黑质致密部（SNc）的神经元密度呈正相关。此外，STN的R1值与其神经元活动呈正相关，但与SNc中DAergic神经元的密度呈负相关。因此，MEMRI的R1值可能是PD严重程度和治疗效果的良好指标。据我们所知，这是第一项表明CEF可预防PD大鼠大脑中神经元活动丧失和神经发生的研究。因此，CEF在PD治疗中可能具有临床潜力。
