n-butylidenephthalide treatment prolongs life span and attenuates motor neuron loss in SOD1G93A mouse model of amyotrophic lateral sclerosis

作者：Zhou, Qin-Ming; Zhang, Jing-Jing; Li, Song; Chen, Sheng^*; Le, Wei-Dong^*

来源：CNS Neuroscience & Therapeutics, 2017, 23(5): 375-385.

DOI：10.1111/cns.12681

• amyotrophic lateral sclerosis
• apoptosis
• inflammation
• n-butylidenephthalide
• oxidative stress

AimsTo evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1(G93A) mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms. @@@ MethodsThe SOD1(G93A) mice were treated by oral administration of BP (q.d., 400mg/kgd) starting from 60days of age and continuing until death. The rotarod test was performed to assess the disease onset. The expression levels of apoptosis-related proteins, inflammatory molecules, and autophagy-associated proteins were determined. The number of apoptotic motor neurons and the extent of microglial and astroglial activation were also assessed in the lumbar spinal cords of BP-treated mice. Grip strength test, hematoxylin-eosin staining, nicotinamide adenine dinucleotide hydrogen staining, and malondialdehyde assay were conducted to evaluate the muscle function and pathology. @@@ ResultsAlthough BP treatment did not delay the disease onset, it prolonged the life span and thereafter extended the disease duration in SOD1(G93A) mouse model of ALS. BP treatment also reduced the motor neuron loss through inhibiting apoptosis. We further demonstrated that the neuroprotective effects of BP might be resulted from the inhibition of inflammatory, oxidative stress, and autophagy. @@@ ConclusionOur study suggests that BP may be a promising candidate for the treatment of ALS.

• 出版日期2017-5
• 单位上海交通大学; 大连医科大学; 上海市闵行区中心医院