Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain
Alzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ<sub>1–42</sub> and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfun...
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doaj-2e6ccef3e15d49ed9389331466c273802021-04-10T23:02:23ZengMDPI AGBiomedicines2227-90592021-04-01940840810.3390/biomedicines9040408Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse BrainInayat Ur Rehman0Riaz Ahmad1Ibrahim Khan2Hyeon Jin Lee3Jungsung Park4Rahat Ullah5Myeong Jun Choi6Hee Young Kang7Myeong Ok Kim8Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaResearch and Development Center, Axceso Bio-pharma co, Anyang 14056, KoreaDepartment of Neurology, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju 52828, KoreaDivision of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, KoreaAlzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ<sub>1–42</sub> and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ<sub>1–42</sub> leads to neuronal inflammation and apoptosis. Since vitamins are basic dietary nutrients that organisms need for their growth, survival, and other metabolic functions, in this study, the underlying neuroprotective mechanism of nicotinamide (NAM) Vitamin B3 against Aβ<sub>1–42</sub> -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ<sub>1–42</sub> injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ<sub>1–42</sub> injection, the mice were treated with NAM (250 mg/kg intraperitoneally) for 1 week. For biochemical and Western blot studies, the mice were directly sacrificed, while for confocal and “immunohistochemical staining”, mice were perfused transcardially with 4% paraformaldehyde. Our biochemical, immunofluorescence, and immunohistochemical results showed that NAM can ameliorate neuronal inflammation and apoptosis by reducing oxidative stress through lowering malondialdehyde and 2,7-dichlorofluorescein levels in an Aβ<sub>1–42</sub>-injected mouse brains, where the regulation of p-JNK further regulated inflammatory marker proteins (TNF-α, IL-1β, transcription factor NF-kB) and apoptotic marker proteins (Bax, caspase 3, PARP1). Furthermore, NAM + Aβ treatment for 1 week increased the amount of survival neurons and reduced neuronal cell death in Nissl staining. We also analyzed memory dysfunction via behavioral studies and the analysis showed that NAM could prevent Aβ<sub>1–42</sub> -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ<sub>1–42</sub> -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model.https://www.mdpi.com/2227-9059/9/4/408oxidative stressneuroinflammationneurodegenerationnicotinamideROS |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inayat Ur Rehman Riaz Ahmad Ibrahim Khan Hyeon Jin Lee Jungsung Park Rahat Ullah Myeong Jun Choi Hee Young Kang Myeong Ok Kim |
spellingShingle |
Inayat Ur Rehman Riaz Ahmad Ibrahim Khan Hyeon Jin Lee Jungsung Park Rahat Ullah Myeong Jun Choi Hee Young Kang Myeong Ok Kim Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain Biomedicines oxidative stress neuroinflammation neurodegeneration nicotinamide ROS |
author_facet |
Inayat Ur Rehman Riaz Ahmad Ibrahim Khan Hyeon Jin Lee Jungsung Park Rahat Ullah Myeong Jun Choi Hee Young Kang Myeong Ok Kim |
author_sort |
Inayat Ur Rehman |
title |
Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain |
title_short |
Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain |
title_full |
Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain |
title_fullStr |
Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain |
title_full_unstemmed |
Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain |
title_sort |
nicotinamide ameliorates amyloid beta-induced oxidative stress-mediated neuroinflammation and neurodegeneration in adult mouse brain |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2021-04-01 |
description |
Alzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ<sub>1–42</sub> and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ<sub>1–42</sub> leads to neuronal inflammation and apoptosis. Since vitamins are basic dietary nutrients that organisms need for their growth, survival, and other metabolic functions, in this study, the underlying neuroprotective mechanism of nicotinamide (NAM) Vitamin B3 against Aβ<sub>1–42</sub> -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ<sub>1–42</sub> injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ<sub>1–42</sub> injection, the mice were treated with NAM (250 mg/kg intraperitoneally) for 1 week. For biochemical and Western blot studies, the mice were directly sacrificed, while for confocal and “immunohistochemical staining”, mice were perfused transcardially with 4% paraformaldehyde. Our biochemical, immunofluorescence, and immunohistochemical results showed that NAM can ameliorate neuronal inflammation and apoptosis by reducing oxidative stress through lowering malondialdehyde and 2,7-dichlorofluorescein levels in an Aβ<sub>1–42</sub>-injected mouse brains, where the regulation of p-JNK further regulated inflammatory marker proteins (TNF-α, IL-1β, transcription factor NF-kB) and apoptotic marker proteins (Bax, caspase 3, PARP1). Furthermore, NAM + Aβ treatment for 1 week increased the amount of survival neurons and reduced neuronal cell death in Nissl staining. We also analyzed memory dysfunction via behavioral studies and the analysis showed that NAM could prevent Aβ<sub>1–42</sub> -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ<sub>1–42</sub> -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model. |
topic |
oxidative stress neuroinflammation neurodegeneration nicotinamide ROS |
url |
https://www.mdpi.com/2227-9059/9/4/408 |
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