Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways
Nicotinamide (NAM) is the amide form of niacin and an important precursor of nicotinamide adenine dinucleotide (NAD), which is needed for energy metabolism and cellular functions. Additionally, it has shown neuroprotective properties in several neurodegenerative diseases. Herein, we sought to invest...
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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2929 |
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| author | Inayat Ur Rehman Amjad Khan Riaz Ahmad Kyonghwan Choe Hyun Young Park Hyeon Jin Lee Abubakar Atiq Jungsung Park Jong Ryeal Hahm Myeong Ok Kim |
| author_facet | Inayat Ur Rehman Amjad Khan Riaz Ahmad Kyonghwan Choe Hyun Young Park Hyeon Jin Lee Abubakar Atiq Jungsung Park Jong Ryeal Hahm Myeong Ok Kim |
| author_sort | Inayat Ur Rehman |
| collection | DOAJ |
| description | Nicotinamide (NAM) is the amide form of niacin and an important precursor of nicotinamide adenine dinucleotide (NAD), which is needed for energy metabolism and cellular functions. Additionally, it has shown neuroprotective properties in several neurodegenerative diseases. Herein, we sought to investigate the potential protective mechanisms of NAM in an intraperitoneal (i.p) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25–30 g). The study had four groups (<i>n</i> = 10 per group): control, MPTP (30 mg/kg i.p. for 5 days), MPTP treated with NAM (500 mg/kg, i.p for 10 days) and control treated with NAM. Our study showed that MPTP increased the expression of α-synuclein 2.5-fold, decreased tyrosine hydroxylase (TH) 0.5-fold and dopamine transporters (DAT) levels up to 0.5-fold in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, NAM treatment significantly reversed these PD-like pathologies. Furthermore, NAM treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) between 0.5- and 1.0-fold. Lastly, NAM treatment regulated neuroinflammation by reducing Toll-like receptor 4 (TLR-4), phosphorylated nuclear factor-κB, tumor (p-NFκB), and cyclooxygenase-2 (COX-2) levels by 0.5- to 2-fold in the PD mouse brain. Overall, these findings suggest that NAM exhibits neuroprotective properties and may be an effective therapeutic agent for PD. |
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| language | English |
| last_indexed | 2024-03-09T18:27:45Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-c82901665a3047a4b03713ca2b5790592023-11-24T07:46:21ZengMDPI AGBiomedicines2227-90592022-11-011011292910.3390/biomedicines10112929Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling PathwaysInayat Ur Rehman0Amjad Khan1Riaz Ahmad2Kyonghwan Choe3Hyun Young Park4Hyeon Jin Lee5Abubakar Atiq6Jungsung Park7Jong Ryeal Hahm8Myeong Ok Kim9Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229 ER Maastricht, The NetherlandsDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital and Institute of Health Sciences and Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju 52828, Republic of KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Republic of KoreaNicotinamide (NAM) is the amide form of niacin and an important precursor of nicotinamide adenine dinucleotide (NAD), which is needed for energy metabolism and cellular functions. Additionally, it has shown neuroprotective properties in several neurodegenerative diseases. Herein, we sought to investigate the potential protective mechanisms of NAM in an intraperitoneal (i.p) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25–30 g). The study had four groups (<i>n</i> = 10 per group): control, MPTP (30 mg/kg i.p. for 5 days), MPTP treated with NAM (500 mg/kg, i.p for 10 days) and control treated with NAM. Our study showed that MPTP increased the expression of α-synuclein 2.5-fold, decreased tyrosine hydroxylase (TH) 0.5-fold and dopamine transporters (DAT) levels up to 0.5-fold in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, NAM treatment significantly reversed these PD-like pathologies. Furthermore, NAM treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) between 0.5- and 1.0-fold. Lastly, NAM treatment regulated neuroinflammation by reducing Toll-like receptor 4 (TLR-4), phosphorylated nuclear factor-κB, tumor (p-NFκB), and cyclooxygenase-2 (COX-2) levels by 0.5- to 2-fold in the PD mouse brain. Overall, these findings suggest that NAM exhibits neuroprotective properties and may be an effective therapeutic agent for PD.https://www.mdpi.com/2227-9059/10/11/2929nicotinamide (NAM)1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)intraperitoneal (i.p)substantia nigra pars compacta (SNpc) |
| spellingShingle | Inayat Ur Rehman Amjad Khan Riaz Ahmad Kyonghwan Choe Hyun Young Park Hyeon Jin Lee Abubakar Atiq Jungsung Park Jong Ryeal Hahm Myeong Ok Kim Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways Biomedicines nicotinamide (NAM) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal (i.p) substantia nigra pars compacta (SNpc) |
| title | Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways |
| title_full | Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways |
| title_fullStr | Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways |
| title_full_unstemmed | Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways |
| title_short | Neuroprotective Effects of Nicotinamide against MPTP-Induced Parkinson’s Disease in Mice: Impact on Oxidative Stress, Neuroinflammation, Nrf2/HO-1 and TLR4 Signaling Pathways |
| title_sort | neuroprotective effects of nicotinamide against mptp induced parkinson s disease in mice impact on oxidative stress neuroinflammation nrf2 ho 1 and tlr4 signaling pathways |
| topic | nicotinamide (NAM) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneal (i.p) substantia nigra pars compacta (SNpc) |
| url | https://www.mdpi.com/2227-9059/10/11/2929 |
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