Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer’s disease
Abstract
Exploring the links between neural pathobiology and behavioural deficits in Alzheimer's disease (AD), and investigating substances with known therapeutic advantages over subcellular mechanisms underlying these dysfunctions could advance the development of potent therapeutic molecules for AD treatment. Here we investigated the efficacy of ascorbic acid (AA) in reversing aluminium chloride (AlCl 3)-induced behavioural deficits and neurotoxic cascades within prefrontal cortex (PFC) and hippocampus of rats. A group of rats administered oral AlCl 3 (100mg/kg) daily for 15days showed degenerative changes characterised by significant weight loss, reduced exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety during behavioural assessments compared to control. Subsequent analysis showed that oxidative impairment-indicated by depleted superoxide dismutase and lipid peroxidation (related to glutathione-S-transferase activity), cholinergic deficits seen by increased neural acetylcholinesterase (AChE) expression and elevated lactate dehydrogenase underlie behavioural alterations. Furthermore, evidences of proteolysis were seen by reduced Nissl profiles in neuronal axons and dendrites which correspond to apoptotic changes observed in H&E staining of PFC and hippocampal sections. Interestingly, AA (100mg/kg daily for 15days) significantly attenuated behavioural deficits in rats through inhibition of molecular and cellular stressor proteins activated by AlCl 3. Our results showed that the primary mechanisms underlying AA therapeutic advantages relates closely with its abilities to scavenge free radicals, prevent membrane lipid peroxidation, modulate neuronal bioenergetics, act as AChE inhibitor and through its anti-proteolytic properties. These findings suggest that supplementing endogenous AA capacity through its pharmacological intake may inhibit progression of AD-related neurodegenerative processes and behavioural alterations.
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Many molecules, including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, have been shown to have anti-inflammatory, anti-amyloidogenic, and anticholinesterase properties.
“Many molecules, including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, have been shown to have anti-inflammatory, anti-amyloidogenic, anticholinesterase, and anti-inflammatory properties.”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Olajide et al., 2017
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Self-citation
- Authors
- Olajide, O. J., Yawson, E. O., Gbadamosi, I. T., Arogundade, T. T., Lambe, E., Obasi, K., Lawal, I. T., Ibrahim, A., & Ogunrinola, K. Y.
- Affiliations
- University of Ilorin (NG)
- Corresponding author
- Olajide, Olayemi Joseph
- ORCID
- Venue
- Environmental Toxicology and Pharmacology
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 50
- Pages
- 200-211
- ISSN
- 1382-6689 (ISSN-L)
- OpenAlex
- W2587096908
- Cited by
- 79
- References
- 64
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 8 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 16 · 2019: 5 · 2018: 2 · 2017: 8
- FWCI
- 6.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Environmental Toxicology and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Olajide Oluwamayokun Oluwatomiyosi for taking time to proofread this manuscript
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Aluminum toxicity and tolerance in plants and animals
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- vitamin C, Alzheimer's disease, aluminum chloride-induced neurotoxicity, behavioural deficits, prefrontal cortex, hippocampus, oxidative stress, lipid peroxidation, acetylcholinesterase, cholinergic deficit, apoptosis, proteolysis, memory impairment, anxiety, neuroprotection
- MeSH terms
- Aluminum Chloride, Alzheimer Disease, Animals, Anxiety, Ascorbic Acid, Chlorides, Disease Models, Animal, Exploratory Behavior, Hippocampus, Humans, Lipid Peroxidation, Prefrontal Cortex, Aluminum Compounds, Disease Progression, Rats
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