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Therapeutic Effects of Selenium on Alpha-Synuclein Accumulation in Substantia Nigra Pars Compacta in a Rat Model of Parkinson’s Disease: Behavioral and Biochemical Outcomes

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Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder characterized by the accumulation of accumulated alpha-synuclein (α-Syn) in substantia nigra. Research has shown that selenium (Se) can protect neural cells through the actions of selenoproteins, including selenoprotein P (SelP) and selenoprotein S (SelS), which participate in endoplasmic reticulum-associated protein degradation (ERAD). In this study, we investigated the potential protective role of Se in a pre-clinical PD rat model.

We aimed to evaluate the therapeutic effects of Se administration in the 6-hydroxydopamine (6-OHDA) induced unilateral rat PD model. Male Wistar rats were utilised for unilateral PD animal model which were subjected to stereotaxic surgery and injected with 20 μg 6-OHDA/5 μl 0.2% ascorbate saline. After confirming the model, the rats were intraperitoneally injected with 0.1, 0.2, and 0.3 mg/kg of sodium selenite for 7 days. We then performed behavioral tests, including apomorphine-induced rotation, hanging, and rotarod tests. Following sacrifice, we analysed the substantia nigra area of the brain and serum for protein quantification, element analysis, and gene expression analysis.

Our results indicate that the administration of 0.3 mg/kg of Se improved the motor deficiency in hanging, rotarod, and apomorphine-induced rotational tests. While there was no significant improvement in the expression of α-Syn, Se increased the expression of selenoproteins. Additionally, levels of selenoproteins, Se, and α-Syn both brain and serum were re-established by the treatment, suggesting the role of Se on the α-Syn accumulation. Furthermore, Se improved PD-induced biochemical deficits by increasing the levels of SelS and SelP (p<0.005).

In conclusion, our findings suggest that Se may have a protective role in PD. 0.3 mg/kg dosage of Se increased the expression of selenoproteins, reduced the accumulation of α-Syn in the brain, and improved PD-induced motor deficits. These results suggest that Se may be a potential therapeutic option for PD treatment.

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Data Availability

All generated or analyzed data during our research are included in this published article. Future data that support the findings are available from the corresponding author, upon reasonable requests.

Abbreviations

α-Syn:

Alpha-synuclein

ApoER2:

Apolipoprotein E receptors 2

cDNA:

Complementary DNA

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

PD:

Parkinson’s disease

PBS:

Phosphate-buffered saline

Se:

Selenium/selenite sodium

SelS:

Selenoprotein S

SelP:

Selenoprotein P

SEPS1/SES1:

Selenoprotein S gene

SEPP1/SEP1:

Selenoprotein P gene

SP/SeP:

Selenoproteins

Sec:

Selenocysteine

Se-Met:

Seleno-L-methionine

SCNA:

α-Syn gene

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

i.p.:

Intraperitoneal

ERAD:

Endoplasmic reticulum-associated protein degradation

6-OHDA:

6-Hydroxydopamine

qRT-PCR:

Real-time quantitative PCR

SNpc:

Substantia nigra pars compacta

RDI:

Recommended daily intake

MFB:

Medial forebrain bundle

ER:

Endoplasmic reticulum

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Acknowledgements

The authors wish to extend special thanks to Kavosh laboratory for assisting with the expert advices to conducting experiments and Dr. Ali Shoeibi for his assistance.

Funding

This work was supported by Mashhad University of Medical Sciences under grant [number 980950]. Dr. Seyed Isaac Hashemy has received the grant.

Author information

Authors and Affiliations

  1. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sanaz Salaramoli

  2. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sanaz Salaramoli & Seyed Isaac Hashemy

  3. Laboratory Sciences Research Centre, Golestan University of Medical Sciences, Gorgan, Iran

    Hamid Reza Joshaghani

  4. Division of Neurocognitive Sciences, Psychiatry and Behavioural Sciences Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahmoud Hosseini

  5. Surgical Oncology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Isaac Hashemy

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  1. Sanaz Salaramoli
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  2. Hamid Reza Joshaghani
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  3. Mahmoud Hosseini
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  4. Seyed Isaac Hashemy
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Contributions

All of the authors contributed to the study conception. The study was designed by Dr. Seyed Isaac Hashemy. Material preparation was performed by Mahmoud Hosseini. Data collection and analysis were performed by Sanaz Salaramoli and Hamid Reza Joshaghani. The first draft of the manuscript was written by Sanaz Salaramoli and revised by Hamid Reza Joshaghani. All of the authors commented on previous versions of the manuscript. All of the authors read and approved the final manuscript.

Corresponding author

Correspondence to Seyed Isaac Hashemy.

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Date of Research Proposal Approval

The research proposal was approved on 2020-07-22.

Ethics Approval

The Animal Research Ethics Committee of the Mashhad university of medical sciences accepted the protocols (Ethic number: IR.MUMS.MEDICAL.REC.1399.345).

Conflict of Interest

The authors declare no competing interests.

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Highlights

1. Se reduces α-Syn accumulation.

2. Se induces SelP and SelS expression.

3. 6OHDA induces α-Syn accumulation in substantia nigra.

4. SelS alleviates α-Syn accumulation.

6. Se has therapeutic effects on PD.

7. Se improves PD-induced motor dysfunctions.

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Salaramoli, S., Joshaghani, H.R., Hosseini, M. et al. Therapeutic Effects of Selenium on Alpha-Synuclein Accumulation in Substantia Nigra Pars Compacta in a Rat Model of Parkinson’s Disease: Behavioral and Biochemical Outcomes. Biol Trace Elem Res 202, 1115–1125 (2024). https://doi.org/10.1007/s12011-023-03748-3

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