Aimee N Winter1, Erika K Ross1, Heather M Wilkins1, Trisha R Stankiewicz1, Tyler Wallace1, Keith Miller2, Daniel A Linseman1,3. 1. a Department of Biological Sciences , Eleanor Roosevelt Institute, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA. 2. b Department of Chemistry and Biochemistry , University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA. 3. c Knoebel Institute for Healthy Aging, University of Denver , 2199 S. University Blvd., Denver , CO 80208 , USA.
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: hSOD1G93A mice 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 hSOD1G93A 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.
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 humanSOD1 (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. 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.
Authors: Lilia A Koza; Aimee N Winter; Jessica Holsopple; Angela N Baybayon-Grandgeorge; Claudia Pena; Jeffrey R Olson; Randall C Mazzarino; David Patterson; Daniel A Linseman Journal: Nutrients Date: 2020-06-18 Impact factor: 5.717
Authors: Jamire M Silva; Michelangela S C Nobre; Sonaly L Albino; Lucas L Lócio; Agnis P S Nascimento; Luciana Scotti; Marcus T Scotti; João A Oshiro-Junior; Maria C A Lima; Francisco J B Mendonça-Junior; Ricardo O Moura Journal: Oxid Med Cell Longev Date: 2020-11-24 Impact factor: 6.543
Authors: Roxana Braga de Andrade Teles; Tâmara Coimbra Diniz; Tiago Coimbra Costa Pinto; Raimundo Gonçalves de Oliveira Júnior; Mariana Gama E Silva; Érica Martins de Lavor; Antonio Wilton Cavalcante Fernandes; Ana Paula de Oliveira; Fernanda Pires Rodrigues de Almeida Ribeiro; Amanda Alves Marcelino da Silva; Taisy Cinthia Ferro Cavalcante; Lucindo José Quintans Júnior; Jackson Roberto Guedes da Silva Almeida Journal: Oxid Med Cell Longev Date: 2018-05-10 Impact factor: 6.543