Aluminum Exposure Induces Time-Dependent Cognitive Decline, Anxiety, and Brain Aluminum Accumulation in Rats

Amirul Hafiz Ahmad Abdullah (Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Husna Anuar (Biomedical Science Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Nur Afiqha Rosli (Biomedical Science Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Hilal Haiqal Faizal (Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Kalaimathy Moothy (Biomedical Science Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Muhammad Hafiz Zuhdi Fairof (Center for Healthy Ageing and Wellness (H-CARE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Nurul Farhana Jufri (Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Siti Fathiah Masre (Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Nor Fadilah Rajab (Biomedical Science Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)
Farah Wahida Ibrahim (Center for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jl Raja Muda Abd Aziz, Kuala Lumpur 50300)

The Indonesian Biomedical Journal
Vol 17, No 5 (2025)

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