scholarly journals Nicotinamide Ameliorates Amyloid Beta-Induced Oxidative Stress-Mediated Neuroinflammation and Neurodegeneration in Adult Mouse Brain

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 408
Author(s):  
Inayat Ur Rehman ◽  
Riaz Ahmad ◽  
Ibrahim Khan ◽  
Hyeon Jin Lee ◽  
Jungsung Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amyloid Beta ◽  
Adult Mouse ◽  
Inflammatory Marker ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Vitamin B3 ◽  
Nissl Staining ◽  
Age Related ◽  
Marker Proteins

Alzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ1–42 and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ1–42 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 Aβ1–42 -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ1–42 injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ1–42 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 Aβ1–42-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 Aβ1–42 -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ1–42 -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model.

scholarly journals Bacopa monnierias an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tamara Simpson ◽  
Matthew Pase ◽  
Con Stough
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Bacopa Monnieri ◽  
Aging Brain ◽  
Resonance Spectroscopy ◽  
Age Related

The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. The Indian herbBacopa monnieriis a dietary antioxidant, with animal andin vitrostudies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts ofBacopa monnieriimprove cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies andin vivoevidence forBacopa monnierias a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant statusin vivocause improvements in cognitive function.

scholarly journals Chronic Treatment of Ascorbic Acid Leads to Age-Dependent Neuroprotection against Oxidative Injury in Hippocampal Slice Cultures

2021 ◽  
Vol 22 (4) ◽  
pp. 1608
Author(s):  
Kyung Hee Lee ◽  
Un Jeng Kim ◽  
Myeounghoon Cha ◽  
Bae Hwan Lee
Keyword(s):  
Oxidative Stress ◽  
Ascorbic Acid ◽  
Hippocampal Neurons ◽  
Hippocampal Slice ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Daily Group ◽  
Age Related ◽  
Signal Activity ◽  
The Brain

Increased oxidative damage in the brain, which increases with age, is the cause of abnormal brain function and various diseases. Ascorbic acid (AA) is known as an endogenous antioxidant that provides neuronal protection against oxidative damage. However, with aging, its extracellular concentrations and uptake decrease in the brain. Few studies have dealt with age-related functional changes in the brain to sustained ascorbate supplementation. This study aimed to investigate the susceptibility of hippocampal neurons to oxidative injury following acute and chronic AA administration. Oxidative stress was induced by kainic acid (KA, 5 µM) for 18 h in hippocampal slice cultures. After KA exposure, less neuronal cell death was observed in the 3 w cultured slice compared to the 9 w cultured slice. In the chronic AA treatment (6 w), the 9 w-daily group showed reduced neuronal cell death and increased superoxide dismutase (SOD) and Nrf2 expressions compared to the 9 w. In addition, the 9 w group showed delayed latencies and reduced signal activity compared to the 3 w, while the 9 w-daily group showed shorter latencies and increased signal activity than the 9 w. These results suggest that the maintenance of the antioxidant system by chronic AA treatment during aging could preserve redox capacity to protect hippocampal neurons from age-related oxidative stress.

Coenzyme Q10 protects against amyloid beta-induced neuronal cell death by inhibiting oxidative stress and activating the P13K pathway

2012 ◽  
Vol 33 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Hojin Choi ◽  
Hyun-Hee Park ◽  
Seong-Ho Koh ◽  
Na-Young Choi ◽  
Hyun-Jeung Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Amyloid Beta ◽  
Coenzyme Q10 ◽  
Neuronal Cell Death ◽  
Neuronal Cell

Oxidative Stress: Major Threat in Traumatic Brain Injury

2018 ◽  
Vol 17 (9) ◽  
pp. 689-695 ◽  
Author(s):  
Nidhi Khatri ◽  
Manisha Thakur ◽  
Vikas Pareek ◽  
Sandeep Kumar ◽  
Sunil Sharma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mitochondrial Dysfunction ◽  
Calcium Influx ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Physical Assault ◽  
Mortality And Morbidity ◽  
Primary Injury

Background & Objective: Traumatic Brain Injury (TBI) is one of the major causes of mortality and morbidity worldwide. It represents mild, moderate and severe effects of physical assault to brain which may cause sequential, primary or secondary ramifications. Primary injury can be due to the first physical hit, blow or jolt to one of the brain compartments. The primary injury is then followed by secondary injury which leads to biochemical, cellular, and physiological changes like blood brain barrier disruption, inflammation, excitotoxicity, necrosis, apoptosis, mitochondrial dysfunction and generation of oxidative stress. Apart from this, there is also an immediate increase in glutamate at the synapses following severe TBI. Excessive glutamate at synapses in turn activates corresponding NMDA and AMPA receptors that facilitate excessive calcium influx into the neuronal cells. This leads to the generation of oxidative stress which further leads to mitochondrial dysfunction, lipid peroxidation and oxidation of proteins and DNA. As a consequence, neuronal cell death takes place and ultimately people start facing some serious disabilies. Conclusion: In the present review we provide extensive overview of the role of reactive oxygen species (ROS)-induced oxidative stress and its fatal effects on brain after TBI.

scholarly journals Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

2021 ◽  
Vol 10 (15) ◽  
pp. 3243
Author(s):  
Rita Del Pinto ◽  
Davide Grassi ◽  
Raffaella Bocale ◽  
Francesco Carubbi ◽  
Claudio Ferri ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Demographic Shift ◽  
Antihypertensive Medications ◽  
Microvascular Damage ◽  
Middle Way ◽  
Alzheimer Type Dementia ◽  
Age Related ◽  
Pressure Profiles

With the demographic shift toward advanced ages, it is imperative to understand the biological mechanisms behind common, disabling age-related diseases such as cognitive impairment in its mild form to overt dementia. Hypertension, a major cardiovascular risk factor, is epidemiologically linked to vascular and Alzheimer-type dementia, with possible mechanisms being atherosclerotic macro- and microvascular damage leading to neuronal cell death, as well as proinflammatory events responsible for neurodegeneration. Nevertheless, there is currently a knowledge gap as to which population to target, what the diagnostics test, and how to manage early pathogenic events in order to prevent such a dramatic and disabling condition. While clinical trials data support the benefit of active BP control with antihypertensive medications on the risk of future cognitive impairment, hypotension appears to be related to accelerated cognitive decline in both the fit and the cognitively frail elderly. Dedicated, technologically advanced studies assessing the relation of BP with dementia are needed to clarify the pathophysiological mechanisms in the association before a tailored preventive, diagnostic, and therapeutic approach to one of the most widespread modern medical challenges becomes a reality.

scholarly journals A Bifunctional Anti-Amyloid Blocks Oxidative Stress and the Accumulation of Intraneuronal Amyloid-Beta

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2010 ◽  
Author(s):  
Silvia Hilt ◽  
Robin Altman ◽  
Tamás Kálai ◽  
Izumi Maezawa ◽  
Qizhi Gong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Small Molecule ◽  
Amyloid Beta ◽  
Disease Process ◽  
Neuronal Cell ◽  
Super Resolution ◽  
Microscopy Imaging ◽  
Neuronal Cell Line ◽  
Intimate Link

There is growing recognition regarding the role of intracellular amyloid beta (Aβ) in the Alzheimer’s disease process, which has been linked with aberrant signaling and the disruption of protein degradation mechanisms. Most notably, intraneuronal Aβ likely underlies the oxidative stress and mitochondrial dysfunction that have been identified as key elements of disease progression. In this study, we employed fluorescence imaging to explore the ability of a bifunctional small molecule to reduce aggregates of intracellular Aβ and attenuate oxidative stress. Structurally, this small molecule is comprised of a nitroxide spin label linked to an amyloidophilic fluorene and is known as spin-labeled fluorene (SLF). The effect of the SLF on intracellular Aβ accumulation and oxidative stress was measured in MC65 cells, a human neuronal cell line with inducible expression of the amyloid precursor protein and in the N2a neuronal cell line treated with exogenous Aβ. Super-resolution microscopy imaging showed SLF decreases the accumulation of intracellular Aβ. Confocal microscopy imaging of MC65 cells treated with a reactive oxygen species (ROS)-sensitive dye demonstrated SLF significantly reduces the intracellular Aβ-induced ROS signal. In order to determine the contributions of the separate SLF moieties to these protective activities, experiments were also carried out on cells with nitroxides lacking the Aβ targeting domain or fluorene derivatives lacking the nitroxide functionality. The findings support a synergistic effect of SLF in counteracting both the conformational toxicity of both endogenous and exogenous Aβ, its promotion of ROS, and Aβ metabolism. Furthermore, these studies demonstrate an intimate link between ROS production and Aβ oligomer formation.

scholarly journals Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1702
Author(s):  
Sereen Sandouka ◽  
Tawfeeq Shekh-Ahmad
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Status Epilepticus ◽  
Temporal Lobe Epilepsy ◽  
Antioxidant Capacity ◽  
Temporal Lobe ◽  
Epileptiform Activity ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
The Brain

Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.

scholarly journals Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells

2019 ◽  
Vol 43 (2) ◽  
pp. 326-334 ◽  
Author(s):  
Dong Hoi Kim ◽  
Dae Won Kim ◽  
Bo Hyun Jung ◽  
Jong Hun Lee ◽  
Heesu Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ht22 Cells ◽  
Ginsenoside Rb2
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