Elevated Oxidative Stress and Decreased Antioxidant Function in the Human Hippocampus and Frontal Cortex with Increasing Age: Implications for Neurodegeneration in Alzheimer’s Disease
Abstract
Oxidative stress and mitochondrial damage are implicated in the evolution of neurodegenerative diseases. Increased oxidative damage in specific brain regions during aging might render the brain susceptible to degeneration. Previously, we demonstrated increased oxidative damage and lowered antioxidant function in substantia nigra during aging making it vulnerable to degeneration associated with Parkinson's disease. To understand whether aging contributes to the vulnerability of brain regions in Alzheimer's disease, we assessed the oxidant and antioxidant markers, glutathione (GSH) metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I (CI) activity in hippocampus (HC) and frontal cortex (FC) compared with cerebellum (CB) in human brains with increasing age (0.01-80 years). We observed significant increase in protein oxidation (HC: p = 0.01; FC: p = 0.0002) and protein nitration (HC: p = 0.001; FC: p = 0.02) and increased GFAP expression (HC: p = 0.03; FC: p = 0.001) with a decreasing trend in CI activity in HC and FC compared to CB with increasing age. These changes were associated with a decrease in antioxidant enzyme activities, such as superoxide dismutase (HC: p = 0.005), catalase (HC: p = 0.02), thioredoxin reductase (FC: p = 0.04), GSH reductase (GR) (HC: p = 0.005), glutathione-s-transferase (HC: p = 0.0001; FC: p = 0.03) and GSH (HC: p = 0.01) with age. However, these parameters were relatively unaltered in CB. We suggest that…
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Hippocampal structural abnormalities and neuronal loss are key neuropathological hallmarks of AD, contributing to cognitive decline.
“Research studies have shown that hippocampal structural abnormalities and neuronal loss are the key neuropathological hallmarks of AD, contributing to the cognitive decline observed in the disease (Venkateshappa et al., 2012; Scheltens et al., 2021).”
From AD-Like Neuropsychiatric Dysfunction in a Mice Model Induced by a Combination of High-Fat Diet and Intraperitoneal Injection of Streptozotocin (2024) · cites this paper as Venkateshappa et al., 2012
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- Authors
- Venkateshappa, C., Harish, G., Mahadevan, A., Srinivas Bharath, M. M., & Shankar, S. K.
- Affiliations
- National Institute of Mental Health and Neurosciences (IN)
- Venue
- Neurochemical Research
- Published
- 2012-03-30
- Volume
- 37
- Issue
- 8
- Pages
- 1601-1614
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2017026767
- Cited by
- 232
- References
- 5
- Citations by year
- 2026: 15 · 2025: 6 · 2024: 18 · 2023: 24 · 2022: 22 · 2021: 23 · 2020: 18 · 2019: 11 · 2018: 10 · 2017: 14 · 2016: 20 · 2015: 12 · 2014: 18 · 2013: 16 · 2012: 5
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health and Neurosciences
- Indian Council of Medical Research
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- oxidative stress, aging, Alzheimer's disease, hippocampus, frontal cortex, cerebellum, antioxidant enzymes, glutathione metabolism, protein oxidation, protein nitration, glial fibrillary acidic protein, mitochondrial complex I, superoxide dismutase, catalase, thioredoxin reductase, glutathione S-transferase, neurodegeneration, brain aging
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Antioxidants, Cerebellum, Child, Child, Preschool, Female, Frontal Lobe, Glial Fibrillary Acidic Protein, Glutathione, Glutathione Transferase, Hippocampus, Humans, Infant, Male, Middle Aged, Mitochondria, Oxidative Stress, Neurodegenerative Diseases, Electron Transport Complex I
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