Abstract
Aluminum (Al) exposure impairs learning and memory function in humans and in animal models. Several studies have shown that the neurotoxicity of Al is associated with damage to mitochondrial morphology and mitochondrial dysfunction, but the molecular mechanism is unclear. The present study was performed to elucidate the possible molecular mechanism related to the Al-induced abnormal mitochondrial dynamics that lead to learning and memory disorders. SD rats were exposed to Al-maltolate complex (Al(mal)3) (blank, 0, 0.41, 0.81, or 1.62 mg/kg) for 30, 60, or 90 days, and neurobehavior, mitochondrial morphology, mitochondrial function, the levels of fission proteins such as dynamin-related protein 1 (Drp1) and fission protein 1 (Fis1), and the levels of fusion proteins such as optic atrophy 1 (Opa1), mitofusin 1 (Mfn1), and mitofusin 2 (Mfn2) were explored. The results indicated that exposure to Al(mal)3 increased the concentration of Al in the brain in a time- and dose-dependent manner and impaired spatial learning and memory. Al(mal)3 damaged mitochondrial morphology and impaired mitochondrial function in the hippocampus. Dose-dependent elevations in the levels of mitochondrial fission (Drp1 and Fis1) and fusion (Opa1, Mfn1, and Mfn2) proteins were observed. In addition, the upregulation of calcineurin (CaN) and the reduced phosphorylation of Drp1 (s637) may have disturbed the balance of mitochondrial fission and fusion in the hippocampus. These results showed that Al-induced learning and memory impairment may be related to mitochondrial fission and fusion disorders.
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Abbreviations
- Al:
-
Aluminum
- COX IV:
-
Cytochrome oxidase IV
- Drp1:
-
Dynamin-related protein 1
- Fis1:
-
Fission protein 1
- Opa1:
-
Optic atrophy 1
- Mfn1:
-
Mitofusin1
- Mfn2:
-
Mitofusin2
- Maltol:
-
3-Hydroxy-2-methyl-4-pyrone
- Al(mal)3 :
-
Aluminum-maltolate complex
- MWM:
-
Morris water maze
- GFAAS:
-
Graphite furnace atomic absorption spectrometry
- TEM:
-
Transmission electron microscopy
- ETC:
-
Electron transport chain
- CaN:
-
Calcineurin
- pDrp1 (s637):
-
Drp1 ser 637 phosphorylation
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We sincerely thank our colleagues for their help and work on the research.
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This research was financially supported by the National Nature Science Foundation of China (No. 81430078 and 81872599).
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The use of rats in this study was approved by the Institutional Animal Care and Use Committee at Shanxi Medical University (Taiyuan, China), and the protocol was approved by the Experimental Animal Ethics Committee of the Shanxi Medical University.
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Nie, J., Lv, S., Fu, X. et al. Effects of Al Exposure on Mitochondrial Dynamics in Rat Hippocampus. Neurotox Res 36, 334–346 (2019). https://doi.org/10.1007/s12640-019-00045-7
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DOI: https://doi.org/10.1007/s12640-019-00045-7