An anthocyanin-enriched extract from strawberries delays disease onset and extends survival in the hSOD(1)(G93A) mouse model of amyotrophic lateral sclerosis

作者：Winter Aimee N; Ross Erika K; Wilkins Heather M; Stankiewicz Trisha R; Wallace Tyler; Miller Keith; Linseman Daniel A^*

来源：Nutritional Neuroscience, 2018, 21(6): 414-426.

DOI：10.1080/1028415X.2017.1297023

• Anthocyanins
• Polyphenols
• Amyotrophic lateral sclerosis
• Neuroprotection
• Neurodegeneration
• Neuroinflammation
• Astrocytes
• Neuromuscular junctions

Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from the death of motor neurons in the brain, brain stem, and spinal cord. Several processes such as oxidative stress, neuroinflammation, and neuronal apoptosis, contribute to disease progression. Anthocyanins are flavonoid compounds derived from fruits and vegetables that possess antioxidant, anti-inflammatory, and antiapoptotic abilities. Thus, these unique compounds may provide therapeutic benefit for the treatment of ALS.
Methods: We used the G93A mutant human SOD1 (hSOD1(G93A)) mouse model of ALS to assess the effects of an anthocyanin-enriched extract from strawberries (SAE) on disease onset and progression. Mice were administered SAE orally beginning at 60 days of age until end-stage such that mice received 2 mg/kg/ day of the extract's primary anthocyanin constituent. Clinical indices of disease were assessed until mice were sacrificed at end-stage. Histopathological indices of disease progression were also evaluated at 105 days of age.
Results: hSOD1(G93A) mice supplemented with SAE experienced a marked (similar to 17 day) delay in disease onset and a statistically significant (similar to 11 day) extension in survival in comparison to their untreated mutant counterparts. Additionally, SAE-treated hSOD1(G93A) mice displayed significantly preserved grip strength throughout disease progression. Histopathological analysis demonstrated that SAE supplementation significantly reduced astrogliosis in spinal cord, and preserved neuromuscular junctions (NMJs) in gastrocnemius muscle.
Discussion: These data are the first to demonstrate that anthocyanins have significant potential as therapeutic agents in a preclinical model of ALS due to their ability to reduce astrogliosis in spinal cord and preserve NMJ integrity and muscle function. Therefore, further study of these compounds is warranted in additional preclinical models of ALS and other neurodegenerative diseases.

• 出版日期2018