title: An anthocyanin-enriched extract from strawberries delays disease onset and extends survival in the hSOD1G93Amouse model of amyotrophic lateral sclerosis.
abstract: 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 anti-apoptotic abilities. Thus, these unique compounds may provide therapeutic benefit for the treatment of ALS.
  
  
  METHODS
  We used the G93A mutant human SOD1 (hSOD1G93A) 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
  hSOD1G93Amice supplemented with SAE experienced a marked (∼17 day) delay in disease onset and a statistically significant (∼11 day) extension in survival in comparison to their untreated mutant counterparts. Additionally, SAE-treated hSOD1G93Amice 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Aimee N
authors.initials: AN
authors.lastname: Winter
authors.affiliation: a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Erika K
authors.initials: EK
authors.lastname: Ross
authors.affiliation: a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Wilkins
authors.affiliation: a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Trisha R
authors.initials: TR
authors.lastname: Stankiewicz
authors.affiliation: a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Wallace
authors.affiliation: b Department of Chemistry and Biochemistry , University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Miller
authors.affiliation: a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.|c Knoebel Institute for Healthy Aging, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Linseman
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000517:prevention & control; D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D001835:Body Weight; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D031985:Fragaria / Q000737:chemistry*; D005911:Gliosis / Q000188:drug therapy / Q000517:prevention & control; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D010936:Plant Extracts; D000072105:Superoxide Dismutase-1
keywords: Amyotrophic lateral sclerosis; Anthocyanins; Astrocytes; Neurodegeneration; Neuroinflammation; Neuromuscular junctions; Neuroprotection; Polyphenols