The Neuroprotective Therapies In SOD1-G93A Mouse Model Of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis(ALS)is a most common and fatal motor neuron disease characterized by the degeneration of both lower and upper motor neurons.The mechanisms underlying ALS pathogenesisare notfully elucidated,and there are not effective treatments for ALS.In the present study,we investigated the therapeutic effects of nbutylidenephthalide(BP)and Huolingshengji Formula(HLSJ)in SOD1-G93 A mouse model of amyotrophic lateral sclerosis and explore the possible mechanisms.BP is one of the main components derived from the volatile oil of Danggui,and it exerts the therapeutic effects on kinds of disease.The SOD1-G93 A mice were treated by gavage with BP from the age of 60 days and continuing till death.We evaluated the effects of BP on disease onset,lifespan,the motor neurons in the anterior horn of lumbar spinal cords and gastrocnemius muscles in SOD1-G93 A mice.Our study demonstrated that BP could prolong the lifespan,slow the disease progression,attenuate the motor neuron loss in the anterior horn of lumbar spinal cords and ameliorate the atrophy of gastrocnemius muscles.The neuroprotective effects of BP may be resulted from the inhibition of apoptosis,inflammation,oxidative stress and autophagy.HLSJ is a traditional Chinese medicine formula that is used for treating flaccid syndrome(also termed as Wei Zheng in Chinese medicine).We developed the fingerprint analysis method of HLSJ which helped determine the main components.The precision,repeatability and stability of fingerprint analysis method were tested.The SOD1-G93 A mice were administrated with HLSJ by gavage from the age of 57 days to the death.It manifested that HLSJ could prolong the lifespan,extend the disease duration,increase the motor neuron survival in the anterior horn of lumbar spinal cords and retard the degeneration of gastrocnemius muscles in SOD1-G93 A mice,which may be related with its activities of anti-apoptosis,anti-inflammation and anti-oxidative stress.In addition,the toxicity test results indicated that HLSJ was safe and had no obvious adverse effect.In conclusion,our study demonstrates that BP and HLSJ have excellent neuroprotective effects in SOD1-G93 A mouse model of ALS.It supports that BP and HLSJ may be novel therapeutic interventions for ALS.