Qin-Ming Zhou1, Jing-Jing Zhang2,3, Song Li2,3, Sheng Chen1,4, Wei-Dong Le1,2,3,5. 1. Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. Liaoning Provincial Clinical Research Center for Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China. 3. Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China. 4. Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Collaborative Innovation Center for Brain Science, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
Abstract
AIMS: To evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1G93A mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms. METHODS: The SOD1G93A mice were treated by oral administration of BP (q.d., 400 mg/kg d) starting from 60 days 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. RESULTS: Although BP treatment did not delay the disease onset, it prolonged the life span and thereafter extended the disease duration in SOD1G93A 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. CONCLUSION: Our study suggests that BP may be a promising candidate for the treatment of ALS.
AIMS: To evaluate the therapeutic effects of n-butylidenephthalide (BP) in SOD1G93A mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms. METHODS: The SOD1G93A mice were treated by oral administration of BP (q.d., 400 mg/kg d) starting from 60 days 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. RESULTS: Although BP treatment did not delay the disease onset, it prolonged the life span and thereafter extended the disease duration in SOD1G93A 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. CONCLUSION: Our study suggests that BP may be a promising candidate for the treatment of ALS.
Authors: Michael C Graves; Milan Fiala; Lu Anne V Dinglasan; Nancy Q Liu; James Sayre; Francesco Chiappelli; Cees van Kooten; Harry V Vinters Journal: Amyotroph Lateral Scler Other Motor Neuron Disord Date: 2004-12
Authors: Janine Kirby; Eugene Halligan; Melisa J Baptista; Simon Allen; Paul R Heath; Hazel Holden; Sian C Barber; Catherine A Loynes; Clare A Wood-Allum; Joseph Lunec; Pamela J Shaw Journal: Brain Date: 2005-05-04 Impact factor: 13.501