Aluminum Exposure Induces Time-Dependent Cognitive Decline, Anxiety, and Brain Aluminum Accumulation in Rats
Year: 2025
Type: article
Abstract: BACKGROUND: Aluminum, a nonessential element, can accumulate in the brain and has been implicated in neurodegenerative disorders such as Alzheimer’s disease (AD). Although previous studies have examined aluminum neurotoxicity, many focus on a single time point, limiting insight into how aluminum accumulates over time. This study addresses that gap by investigating time-dependent aluminum accumulation and associated neurobehavioral changes in rats at 14, 28, and 42 days.METHODS: Male Wistar rats were administered 200 mg/kg/day aluminum chloride (AlCl3) via oral gavage for 14 (acute), 28 (subacute), and 42 (subchronic) days. Cognitive and anxiety-like behaviors were assessed using the 2-novel object recognition (2NOR) test, spontaneous alternation Y-maze, and open field test (OFT). Brain aluminum levels were quantified using inductively coupled plasma mass spectrometry (ICP-MS).RESULTS: There were impairments in spatial and non-spatial memory and increased anxiety-like behavior across all exposure durations (p<0.05). Non-spatial memory performance decreased by 50.5%, 37.7%, and 56.2% on day-14, -28, and -42, respectively. Spatial memory significantly declined by 34.3% and 43.2% on day-14 and -42, respectively, while the 20.0% decrease at day-28 was not statistically significant. Anxiety-like behavior increased, with center zone entries reduced by 37.6%, 64.9%, and 62.9% across the same time points. Brain aluminum concentrations were significantly elevated in all aluminum-exposed groups compared to controls, with increases of 2,622.6%, 314.7%, and 969.3% on day-14, -28, and -42, respectively (p<0.05). The increase was not strictly proportional to exposure duration, suggesting possible homeostatic regulation. Weight and liver assessments confirmed the subtoxic nature of the exposure.CONCLUSION: Exposure to aluminum for 42 days induces behavioral deficits and increases brain aluminum levels, which may support its potential relevance as a model to study aluminum-induced neurotoxicity.KEYWORDS: aluminum exposure, cognitive function, anxiety, temporal progression, neurobehavioral changes
Authors: Amirul Hafiz Ahmad Abdullah, Husna Anuar, Nur Afiqha Rosli, Hilal Haiqal Faizal, Kalaimathy Moothy, Muhammad Hafiz Zuhdi Fairof, Nurul Farhana Jufri, Siti Fathiah Masre, Nor Fadilah Rajab, Farah Wahida Ibrahim
Institution: National University of Malaysia
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $200
OpenAlex ID: W4415650575