Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model
Parkinson’s disease (PD) is the second most common neurodegenerative disease. Treatment of PD is challenging, as current treatment strategies are only symptomatic and do not stop disease development. Recent studies reported neuroprotective effects of calcitriol in PD through its antioxidant and anti...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2022.967813/full |
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| author | Alshimaa Magdy Eman A. E. Farrag Shereen Mohamed Hamed Zienab Abdallah Eman Mohamad El Nashar Eman Mohamad El Nashar Mansour Abdullah Alghamdi Mansour Abdullah Alghamdi Amira A. H. Ali Amira A. H. Ali Marwa Abd El-kader |
| author_facet | Alshimaa Magdy Eman A. E. Farrag Shereen Mohamed Hamed Zienab Abdallah Eman Mohamad El Nashar Eman Mohamad El Nashar Mansour Abdullah Alghamdi Mansour Abdullah Alghamdi Amira A. H. Ali Amira A. H. Ali Marwa Abd El-kader |
| author_sort | Alshimaa Magdy |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is the second most common neurodegenerative disease. Treatment of PD is challenging, as current treatment strategies are only symptomatic and do not stop disease development. Recent studies reported neuroprotective effects of calcitriol in PD through its antioxidant and anti-inflammatory properties. The exact pathomechanisms of PD are not yet fully understood. So, investigation of different molecular pathways is challenging. Sirtuin-1 (Sirt1) modulates multiple physiological processes, including programmed cell death, DNA repair, and inflammation. Furthermore, defective autophagy is considered a key pathomechanism in PD as it eliminates protein aggregation and dysfunctional cell organelles. The present study investigated the involvement of autophagy and Sirt1/NF-κB molecular pathway in rotenone-induced PD and explored the protective and restorative effects of calcitriol through these mechanisms. Therefore, behavioral tests were used to test the effect of calcitriol on motor disability and equilibrium. Furthermore, the histological and neuronal architecture was assessed. The expression of genes encoding neuroinflammation and autophagy markers was determined by qPCR while their protein levels were determined by Western blot analysis and immune-histochemical staining. Our results indicate that behavioral impairments and dopaminergic neuron depletion in the rotenone-induced PD model were improved by calcitriol administration. Furthermore, calcitriol attenuated rotenone-induced neuroinflammation and autophagy dysfunction in PD rats through up-regulation of Sirt1 and LC3 and down-regulation of P62 and NF-κB expression levels. Thus, calcitriol could induce a neuro-protective and restorative effect in the rotenone-induced PD model by modulating autophagy and Sirt1/NF-κB pathway. |
| first_indexed | 2024-04-12T19:05:32Z |
| format | Article |
| id | doaj.art-d8a316202f3e4b33a843189d4cfd60da |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T19:05:32Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-d8a316202f3e4b33a843189d4cfd60da2022-12-22T03:20:02ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022022-09-011610.3389/fncel.2022.967813967813Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat modelAlshimaa Magdy0Eman A. E. Farrag1Shereen Mohamed Hamed2Zienab Abdallah3Eman Mohamad El Nashar4Eman Mohamad El Nashar5Mansour Abdullah Alghamdi6Mansour Abdullah Alghamdi7Amira A. H. Ali8Amira A. H. Ali9Marwa Abd El-kader10Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Medical Histology, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, EgyptDepartment of Anatomy, College of Medicine, King Khalid University, Abha, Saudi ArabiaDepartment of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, EgyptDepartment of Anatomy, College of Medicine, King Khalid University, Abha, Saudi ArabiaGenomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha, Saudi ArabiaDepartment of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, EgyptInstitute of Anatomy ll, Medical Faculty, Heinrich Heine University, Düsseldorf, GermanyDepartment of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, EgyptParkinson’s disease (PD) is the second most common neurodegenerative disease. Treatment of PD is challenging, as current treatment strategies are only symptomatic and do not stop disease development. Recent studies reported neuroprotective effects of calcitriol in PD through its antioxidant and anti-inflammatory properties. The exact pathomechanisms of PD are not yet fully understood. So, investigation of different molecular pathways is challenging. Sirtuin-1 (Sirt1) modulates multiple physiological processes, including programmed cell death, DNA repair, and inflammation. Furthermore, defective autophagy is considered a key pathomechanism in PD as it eliminates protein aggregation and dysfunctional cell organelles. The present study investigated the involvement of autophagy and Sirt1/NF-κB molecular pathway in rotenone-induced PD and explored the protective and restorative effects of calcitriol through these mechanisms. Therefore, behavioral tests were used to test the effect of calcitriol on motor disability and equilibrium. Furthermore, the histological and neuronal architecture was assessed. The expression of genes encoding neuroinflammation and autophagy markers was determined by qPCR while their protein levels were determined by Western blot analysis and immune-histochemical staining. Our results indicate that behavioral impairments and dopaminergic neuron depletion in the rotenone-induced PD model were improved by calcitriol administration. Furthermore, calcitriol attenuated rotenone-induced neuroinflammation and autophagy dysfunction in PD rats through up-regulation of Sirt1 and LC3 and down-regulation of P62 and NF-κB expression levels. Thus, calcitriol could induce a neuro-protective and restorative effect in the rotenone-induced PD model by modulating autophagy and Sirt1/NF-κB pathway.https://www.frontiersin.org/articles/10.3389/fncel.2022.967813/fullrotenoneParkinson’sSirt1NF-kBautophagyvitamin D |
| spellingShingle | Alshimaa Magdy Eman A. E. Farrag Shereen Mohamed Hamed Zienab Abdallah Eman Mohamad El Nashar Eman Mohamad El Nashar Mansour Abdullah Alghamdi Mansour Abdullah Alghamdi Amira A. H. Ali Amira A. H. Ali Marwa Abd El-kader Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model Frontiers in Cellular Neuroscience rotenone Parkinson’s Sirt1 NF-kB autophagy vitamin D |
| title | Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model |
| title_full | Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model |
| title_fullStr | Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model |
| title_full_unstemmed | Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model |
| title_short | Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson’s disease rat model |
| title_sort | neuroprotective and therapeutic effects of calcitriol in rotenone induced parkinson s disease rat model |
| topic | rotenone Parkinson’s Sirt1 NF-kB autophagy vitamin D |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2022.967813/full |
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