Effects of (−)-epicatechin on neuroinflammation and hyperphosphorylation of tau in the hippocampus of aged mice
Autor: | Alejandra Garate-Carrillo, Alonso Rodriguez, Claudia C. Calzada-Mendoza, Viridiana Navarrete-Yañez, Michael C. Hogan, Israel Ramirez-Sanchez, Patricia Mendoza-Lorenzo, Guillermo Ceballos, Francisco Villarreal |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Aging medicine.medical_specialty Tau protein Anti-Inflammatory Agents Hyperphosphorylation tau Proteins Inflammation medicine.disease_cause Systemic inflammation Hippocampus Article Catechin Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Glial Fibrillary Acidic Protein medicine Animals Phosphorylation Neuroinflammation Amyloid beta-Peptides biology Glial fibrillary acidic protein Chemistry General Medicine Mice Inbred C57BL Oxidative Stress 030104 developmental biology Endocrinology Nerve growth factor biology.protein Cytokines medicine.symptom 030217 neurology & neurosurgery Oxidative stress Food Science |
Zdroj: | Food Funct |
ISSN: | 2042-650X 2042-6496 |
DOI: | 10.1039/d0fo02438d |
Popis: | Evidence has implicated oxidative stress (OS) and inflammation as drivers of neurodegenerative pathologies. We previously reported on the beneficial effects of (-)-epicatechin (Epi) treatment on aging-induced OS and its capacity to restore modulators of mitochondrial biogenesis in the prefrontal cortex of 26-month-old male mice. In the present study using the same mouse model of aging, we examined the capacity of Epi to mitigate hippocampus OS, inflammation, hyperphosphorylation of tau protein, soluble β-amyloid protein levels, cell survival, memory, anxiety-like behavior levels and systemic inflammation. Mice were subjected to 4 weeks of Epi treatment (1 mg kg-1 day-1) and samples of the hippocampus were obtained. Assessments of the OS markers, protein carbonyls, and malondialdehyde levels demonstrated their significant increase (∼3 fold) with aging that were partially suppressed by Epi. The protein levels of the glial fibrillary acidic protein, inflammatory factor 1 (Iba1), pro-inflammatory cytokines, interleukins (IL-1β, IL-3, 5, 6 and 15), cyclooxygenase 2, tumor necrosis factor α, nuclear factor-activated B cells and interferon γ increase with aging and were also significantly decreased with Epi treatment. However, anti-inflammatory cytokines, IL-1ra, IL-10 and 11 decrease with aging and were restored with Epi. Epi also reversed the aging effects on the hyperphosphorylation of tau, increased soluble β-amyloid levels (∼2 fold), cellular death (as per caspase 3 and 9 activity), and reduced nerve growth factor and triggering receptor expressed on myeloid cells 2 levels. Measures of anxiety like-behavior and memory demonstrated improvements with Epi treatment. Indicators of systemic inflammation increase with aging and Epi was capable of decreasing blood inflammatory markers. Altogether, the results show a significant capacity of Epi to mitigate hippocampus OS and inflammation leading to improved brain function. |
Databáze: | OpenAIRE |
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