Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects
Parkinson’s disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD is a complex disease that deteriorates patients’ motor and non-motor functions. In experimental animals, the neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical and mitochondrial abnorma...
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MDPI AG
2022-11-01
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| author | Metab Alharbi Abdulrahman Alshammari Gurpreet Kaur Sanjeev Kalra Sidharth Mehan Manisha Suri Swesha Chhabra Nitish Kumar Wael A. Alanazi Aliah R. Alshanwani Abdullah Hamed AL-Ghamdi Acharan S. Narula Reni Kalfin |
| author_facet | Metab Alharbi Abdulrahman Alshammari Gurpreet Kaur Sanjeev Kalra Sidharth Mehan Manisha Suri Swesha Chhabra Nitish Kumar Wael A. Alanazi Aliah R. Alshanwani Abdullah Hamed AL-Ghamdi Acharan S. Narula Reni Kalfin |
| author_sort | Metab Alharbi |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD is a complex disease that deteriorates patients’ motor and non-motor functions. In experimental animals, the neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical and mitochondrial abnormalities and the formation of free radicals, which is related to Parkinson-like symptoms after inter-striatal 6-OHDA injection. Pathological manifestations of PD disrupt the cAMP/ATP-mediated activity of the transcription factor CREB, resulting in Parkinson’s-like symptoms. Forskolin (FSK) is a direct AC/cAMP/CREB activator isolated from <i>Coleus forskohlii</i> with various neuroprotective properties. FSK has already been proven in our laboratory to directly activate the enzyme adenylcyclase (AC) and reverse the neurodegeneration associated with the progression of Autism, Multiple Sclerosis, ALS, and Huntington’s disease. Several behavioural paradigms were used to confirm the post-lesion effects, including the rotarod, open field, grip strength, narrow beam walk (NBW) and Morris water maze (MWM) tasks. Our results were supported by examining brain cellular, molecular, mitochondrial and histopathological alterations. The FSK treatment (15, 30 and 45 mg/kg, orally) was found to be effective in restoring behavioural and neurochemical defects in a 6-OHDA-induced experimental rat model of PD. As a result, the current study successfully contributes to the investigation of FSK’s neuroprotective role in PD prevention via the activation of the AC/cAMP/PKA-driven CREB pathway and the restoration of mitochondrial ETC-complex enzymes. |
| first_indexed | 2024-03-09T18:06:45Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:06:45Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3886762cff8e4177a2522bf5b7cdaab02023-11-24T09:23:55ZengMDPI AGMolecules1420-30492022-11-012722795110.3390/molecules27227951Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological DefectsMetab Alharbi0Abdulrahman Alshammari1Gurpreet Kaur2Sanjeev Kalra3Sidharth Mehan4Manisha Suri5Swesha Chhabra6Nitish Kumar7Wael A. Alanazi8Aliah R. Alshanwani9Abdullah Hamed AL-Ghamdi10Acharan S. Narula11Reni Kalfin12Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology, Rajendra Institute of Technology and Sciences, Hisar Road, 4th Mile Stone, Sirsa, Haryana 125055, IndiaDepartment of Pharmacology, Rajendra Institute of Technology and Sciences, Hisar Road, 4th Mile Stone, Sirsa, Haryana 125055, IndiaDepartment of Pharmacology, Rajendra Institute of Technology and Sciences, Hisar Road, 4th Mile Stone, Sirsa, Haryana 125055, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, Riyadh 11451, Saudi ArabiaPhysiology Department, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh 12372, Saudi ArabiaPharmaceutical Care Department, Namerah General Hospital, Ministry of Health, Namerah 65439, Saudi ArabiaNarula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USAInstitute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, 1113 Sofia, BulgariaParkinson’s disease (PD) is characterised by dopaminergic neuronal loss in the brain area. PD is a complex disease that deteriorates patients’ motor and non-motor functions. In experimental animals, the neurotoxin 6-OHDA induces neuropathological, behavioural, neurochemical and mitochondrial abnormalities and the formation of free radicals, which is related to Parkinson-like symptoms after inter-striatal 6-OHDA injection. Pathological manifestations of PD disrupt the cAMP/ATP-mediated activity of the transcription factor CREB, resulting in Parkinson’s-like symptoms. Forskolin (FSK) is a direct AC/cAMP/CREB activator isolated from <i>Coleus forskohlii</i> with various neuroprotective properties. FSK has already been proven in our laboratory to directly activate the enzyme adenylcyclase (AC) and reverse the neurodegeneration associated with the progression of Autism, Multiple Sclerosis, ALS, and Huntington’s disease. Several behavioural paradigms were used to confirm the post-lesion effects, including the rotarod, open field, grip strength, narrow beam walk (NBW) and Morris water maze (MWM) tasks. Our results were supported by examining brain cellular, molecular, mitochondrial and histopathological alterations. The FSK treatment (15, 30 and 45 mg/kg, orally) was found to be effective in restoring behavioural and neurochemical defects in a 6-OHDA-induced experimental rat model of PD. As a result, the current study successfully contributes to the investigation of FSK’s neuroprotective role in PD prevention via the activation of the AC/cAMP/PKA-driven CREB pathway and the restoration of mitochondrial ETC-complex enzymes.https://www.mdpi.com/1420-3049/27/22/7951adenylcyclaseCREBforskolinmitochondrial abnormalitiesParkinson’s disease |
| spellingShingle | Metab Alharbi Abdulrahman Alshammari Gurpreet Kaur Sanjeev Kalra Sidharth Mehan Manisha Suri Swesha Chhabra Nitish Kumar Wael A. Alanazi Aliah R. Alshanwani Abdullah Hamed AL-Ghamdi Acharan S. Narula Reni Kalfin Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects Molecules adenylcyclase CREB forskolin mitochondrial abnormalities Parkinson’s disease |
| title | Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects |
| title_full | Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects |
| title_fullStr | Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects |
| title_full_unstemmed | Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects |
| title_short | Effect of Natural Adenylcyclase/cAMP/CREB Signalling Activator Forskolin against Intra-Striatal 6-OHDA-Lesioned Parkinson’s Rats: Preventing Mitochondrial, Motor and Histopathological Defects |
| title_sort | effect of natural adenylcyclase camp creb signalling activator forskolin against intra striatal 6 ohda lesioned parkinson s rats preventing mitochondrial motor and histopathological defects |
| topic | adenylcyclase CREB forskolin mitochondrial abnormalities Parkinson’s disease |
| url | https://www.mdpi.com/1420-3049/27/22/7951 |
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