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Post-exposure self-recovery reverses oxidative stress, ameliorates pathology and neurotransmitters imbalance and rescues spatial memory after time-dependent aluminum exposure in rat brain

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Abstract

Aluminum is a potent neurotoxin, responsible for memory impairment and cognitive dysfunction. The neurotoxic effect of aluminum on cognitive impairment is well documented, however, exposure to aluminum in a time-dependent manner and post-exposure self-recovery still needs to be elaborated. This research aimed to (1) study the time-dependent effect of aluminum exposure by administering a total dose of 5850 mg/kg of Al over two different time periods: 30 and 45 days (130 and 195 mg/kg of AlCl3 respectively), and (2) study 20 days post-exposure self-recovery effect in both aluminum-exposed groups by giving distilled water. Cognitive abilities were investigated through Morris water maze test and hole board test and compared in both exposure and recovery groups. Oxidative stress markers and neurotransmitter levels were measured for both exposure and recovery groups. To understand the mechanism of aluminum exposure and recovery, immunohistochemical analysis of synaptophysin (Syp) and glial fibrillary acidic protein (GFAP) was performed. Results showed cognitive dysfunction, oxidative stress-induced damage, reduced neurotransmitter levels, decreased immunoreactivity of Syp, and increased GFAP. However, these parameters showed a larger improvement in the recovery group where rats were given aluminum for 30 days period in comparison to recovery group followed by 45 days of aluminum exposure. These results suggest that restoration of cognitive ability is affected by the duration of aluminum exposure. The study findings provide us with insight into the adverse effects of aluminum exposure and can be utilized to guide future preventive and therapeutic strategies against aluminum neurotoxicity.

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Abbreviations

Al:

Aluminum

CAT:

Catalase

SOD:

Superoxide dismutase

GPx:

Glutathione peroxidase

MDA:

Malondialdehyde

LPO:

Lipid peroxidation

NA:

Noradrenaline

DA:

Dopamine

DOPAC:

Dihydroxyphenyl acetic acid

5-HT:

5-Hydroxytryptamine

5-HIAA:

5-Hydroxyindoleacetic acid

DG:

Dentate gyrus

Syp:

Synaptophysin

GFAP:

Glial fibrillary protein

HBT:

Hole board test

TQ:

Target quadrant

MWM:

Morris water maze test

RME:

Reference memory error

WME:

Working memory error

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Acknowledgements

We like to express our sincere gratitude to Saba Mehak Zahoor (MSc Neurosciences), King’s College London, UK, for her valuable assistance in proofreading and English language editing. We like to acknowledge Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Pakistan, and Higher Education Commission (HEC) of Pakistan for providing support and facilities for this study. First author is recipient of Indigenous 5000 PhD Scholarship program, HEC. HEC is not involved in study design, data interpretation, writing of manuscript, and decision to submit article for publication.

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Authors and Affiliations

  1. Neurobiology Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Sector H-12, Islamabad, 44000, Pakistan

    Humna Asghar, Alveena Siddiqui & Touqeer Ahmed

  2. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan

    Laraib Batool & Zehra Batool

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  1. Humna Asghar
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  2. Alveena Siddiqui
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  3. Laraib Batool
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  4. Zehra Batool
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Contributions

Humna Asghar: Data curation, Writing - original draft, Investigation, Methodology, Data interpretation, Writing - review & editing. Alveena Siddiqui, Laraib Batool, Zehra Batool: Methodology and Data interpretation. Touqeer Ahmed: Conceptualization, Investigation, Supervision, Writing - review & editing.

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Correspondence to Touqeer Ahmed.

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Asghar, H., Siddiqui, A., Batool, L. et al. Post-exposure self-recovery reverses oxidative stress, ameliorates pathology and neurotransmitters imbalance and rescues spatial memory after time-dependent aluminum exposure in rat brain. Biometals (2024). https://doi.org/10.1007/s10534-023-00570-1

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