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Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, β-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats

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Abstract

The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, β-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500 mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aβ peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aβ plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

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Data Availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Contributions

MZ: Conceptualization, Methodology, Formal analysis, Data curation, Resources, Writing – original draft, Writing – review & editing, Supervision. FF: Investigation, Validation, Formal analysis, Data curation, Writing – original draft. EA: Formal analysis, Investigation. ASh: Formal analysis, Data curation. EA: Formal analysis, Validation. FF: Formal analysis, Investigation. AW: Resources, Writing – review & editing, Funding acquisition. ZDN: Formal analysis, Investigation. Ali AA and FA: Resources, Writing – review & editing, Supervision, Project administration, Funding acquisition.

Corresponding author

Correspondence to Mehdi Zargani.

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Ethical Approval

All methods were used in accordance with the Guidelines for the Care and Use of Laboratory Animals (NIH publication No. 80 − 23, revised 1996) and approved by the Institutional Animal Care and Use Committee (IACUC) of Azad University (Karaj, Iran) (Code of Ethics: IR.IAU.K.REC.1401.037).

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The authors declare no competing interests.

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Feizolahi, F., Arabzadeh, E., Sarshin, A. et al. Effects of Exercise Training and L-Arginine Loaded Chitosan Nanoparticles on Hippocampus Histopathology, β-Secretase Enzyme Function, APP, Tau, Iba1and APOE-4 mRNA in Aging Rats. Neurotox Res 42, 21 (2024). https://doi.org/10.1007/s12640-024-00699-y

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  • DOI: https://doi.org/10.1007/s12640-024-00699-y

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