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Retinoic Acid Prevents the Neuronal Damage Through the Regulation of Parvalbumin in an Ischemic Stroke Model

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Abstract

Ischemic stroke is a neurological disease that causes brain damage by increasing oxidative stress and ion imbalance. Retinoic acid is a major metabolite of vitamin A and regulates oxidative stress, calcium homeostasis, and cell death. Intracellular calcium is involved in neuronal growth and synaptic plasticity. Parvalbumin is a calcium-binding protein that is mainly expressed in brain. In this study, we investigated whether retinoic acid has neuroprotective effects by controlling intracellular calcium concentration and parvalbumin expression in ischemic brain damage. Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected into the abdominal cavity for four days before surgery and cerebral cortices were collected 24 h after MCAO for further studies. MCAO damage induced neurological deficits and histopathological changes and decreased parvalbumin expression. However, retinoic acid treatment alleviated these changes. In cultured neurons, glutamate (5 mM) exposure induced neuronal cell death, increased intracellular calcium concentration, and decreased parvalbumin expression. Retinoic acid treatment attenuated these changes against glutamate toxicity in a dose-dependent manner. It also regulates glutamate induced change in bcl-2 and bax expression. The mitigation effects of retinoic acid were greater under non-transfection conditions than under parvalbumin siRNA transfection conditions. Our findings showed that retinoic acid modulates intracellular calcium concentration and parvalbumin expression and prevents apoptosis in ischemic brain injury. In conclusion, retinoic acid contributes to the preservation of neurons from ischemic stroke by controlling parvalbumin expression and apoptosis-related proteins.

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Funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government [MEST][NRF-2021R1F1A105878711].

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Authors and Affiliations

  1. Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, 501 Jinjudaero, Jinju, 52828, South Korea

    Ju-Bin Kang, Dong-Ju Park & Phil-Ok Koh

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  1. Ju-Bin Kang
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  2. Dong-Ju Park
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  3. Phil-Ok Koh
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Contributions

All authors contributed to the study conception and design. Data collection, analysis, and manuscript writing were performed by JK. Material preparation and data collection were performed by DP. PK wrote and supervised the research. All authors read and approved the manuscript.

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Correspondence to Phil-Ok Koh.

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Kang, JB., Park, DJ. & Koh, PO. Retinoic Acid Prevents the Neuronal Damage Through the Regulation of Parvalbumin in an Ischemic Stroke Model. Neurochem Res 48, 487–501 (2023). https://doi.org/10.1007/s11064-022-03769-9

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