Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease
IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail to halt disease progression, highlighting the need for novel the...
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Frontiers Media S.A.
2025-01-01
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| author | Yong Hui Nies Wei Ling Lim Norwahidah Abd Karim Mohamad Fairuz Yahaya Seong Lin Teoh |
| author_facet | Yong Hui Nies Wei Ling Lim Norwahidah Abd Karim Mohamad Fairuz Yahaya Seong Lin Teoh |
| author_sort | Yong Hui Nies |
| collection | DOAJ |
| description | IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail to halt disease progression, highlighting the need for novel therapeutic strategies. This study explores the neuroprotective potential of exogenous human metallothionein 2 (hMT2) peptide in a rotenone-induced PD zebrafish model.MethodsAdult zebrafish were divided into four groups: control, rotenone-treated, hMT2 pre-treatment, and hMT2 co-treatment. PD model was established by exposing zebrafish to 5 µg/L rotenone water for 28 days. hMT2 (0.2 µg) was administered intracranially either one day before or seven days after rotenone exposure.ResultsThe novel tank test demonstrated that rotenone exposure significantly impaired locomotor activity (p < 0.05) and increased anxiety-like behavior (p < 0.001). Additionally, PD model zebrafish exhibited reduced dopamine levels, decreased dopaminergic neuron population, elevated oxidative stress, heightened inflammatory response and mitochondrial dysfunction. Treatment with hMT2, especially in the co-treatment group, ameliorated these deficits by restoring locomotor activity, dopamine levels, and dopaminergic neuron counts while reducing oxidative stress and inflammation, and improving mitochondrial function.DiscussionThese results suggest that hMT2 exhibited neuroprotective effect in the PD model zebrafish. These findings support the potential of MT as a therapeutic agent for PD. |
| format | Article |
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| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-7e48574e64c94847a2f7e77469904c3e2025-01-31T06:39:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.14780131478013Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s diseaseYong Hui Nies0Wei Ling Lim1Norwahidah Abd Karim2Mohamad Fairuz Yahaya3Seong Lin Teoh4Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Biological Sciences, School of Medical and Life Sciences, Sunway University, Petaling Jaya, MalaysiaDepartment of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaDepartment of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, MalaysiaIntroductionParkinson’s disease (PD) is a common neurodegenerative disorder primarily affecting motor function due to progressive loss of dopaminergic neurons in the substantia nigra. Current therapies offer symptomatic relief but fail to halt disease progression, highlighting the need for novel therapeutic strategies. This study explores the neuroprotective potential of exogenous human metallothionein 2 (hMT2) peptide in a rotenone-induced PD zebrafish model.MethodsAdult zebrafish were divided into four groups: control, rotenone-treated, hMT2 pre-treatment, and hMT2 co-treatment. PD model was established by exposing zebrafish to 5 µg/L rotenone water for 28 days. hMT2 (0.2 µg) was administered intracranially either one day before or seven days after rotenone exposure.ResultsThe novel tank test demonstrated that rotenone exposure significantly impaired locomotor activity (p < 0.05) and increased anxiety-like behavior (p < 0.001). Additionally, PD model zebrafish exhibited reduced dopamine levels, decreased dopaminergic neuron population, elevated oxidative stress, heightened inflammatory response and mitochondrial dysfunction. Treatment with hMT2, especially in the co-treatment group, ameliorated these deficits by restoring locomotor activity, dopamine levels, and dopaminergic neuron counts while reducing oxidative stress and inflammation, and improving mitochondrial function.DiscussionThese results suggest that hMT2 exhibited neuroprotective effect in the PD model zebrafish. These findings support the potential of MT as a therapeutic agent for PD.https://www.frontiersin.org/articles/10.3389/fphar.2025.1478013/fullneurodegenerative diseaseneuroprotectionpesticidedopaminergic neuronmitochondrial function |
| spellingShingle | Yong Hui Nies Wei Ling Lim Norwahidah Abd Karim Mohamad Fairuz Yahaya Seong Lin Teoh Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease Frontiers in Pharmacology neurodegenerative disease neuroprotection pesticide dopaminergic neuron mitochondrial function |
| title | Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease |
| title_full | Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease |
| title_fullStr | Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease |
| title_full_unstemmed | Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease |
| title_short | Metallothionein II treatment mitigates rotenone-induced neurodegeneration in zebrafish models of Parkinson’s disease |
| title_sort | metallothionein ii treatment mitigates rotenone induced neurodegeneration in zebrafish models of parkinson s disease |
| topic | neurodegenerative disease neuroprotection pesticide dopaminergic neuron mitochondrial function |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1478013/full |
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