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 17β-Estradiol Modulates SIRT1 and Halts Oxidative Stress-Mediated Cognitive Impairment in a Male Aging Mouse Model

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 928 ◽  
Author(s):  
Mehtab Khan ◽  
Rahat Ullah ◽  
Shafiq Ur Rehman ◽  
Shahid Ali Shah ◽  
Kamran Saeed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Memory Impairment ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ros Generation ◽  
Dependent Manner ◽  
Molecular Docking Study ◽  
17Β Estradiol

Oxidative stress has been considered the main mediator in neurodegenerative disease and in normal aging processes. Several studies have reported that the accumulation of reactive oxygen species (ROS), elevated oxidative stress, and neuroinflammation result in cellular malfunction. These conditions lead to neuronal cell death in aging-related neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease. Chronic administration of d-galactose (d-gal) for a period of 10 weeks causes ROS generation and neuroinflammation, ultimately leading to cognitive impairment. In this study, we evaluated the estrogen receptor α (ERα)/silent mating type information regulation 2 homolog 1 (SIRT1)-dependent antioxidant efficacy of 17β-estradiol against d-gal-induced oxidative damage-mediated cognitive dysfunction in a male mouse model. The results indicate that 17β-estradiol, by stimulating ERα/SIRT1, halts d-gal-induced oxidative stress–mediated JNK/NF-ҡB overexpression, neuroinflammation and neuronal apoptosis. Moreover, 17β-estradiol ameliorated d-gal-induced AD-like pathophysiology, synaptic dysfunction and memory impairment in adult mouse brains. Interestingly, inhibition of SIRT1 with Ex527 (a potent and selective SIRT1 inhibitor) further enhanced d-gal-induced toxicity and abolished the beneficial effect of 17β-estradiol. Most importantly, for the first time, our molecular docking study reveals that 17β-estradiol allosterically increases the expression of SIRT1 and abolishes the inhibitory potential of d-ga. In summary, we can conclude that 17β-estradiol, in an ERα/SIRT1-dependent manner, abrogates d-gal-induced oxidative stress–mediated memory impairment, neuroinflammation, and neurodegeneration in adult mice.

From tau phosphorylation to tau aggregation: what about neuronal death?

2010 ◽  
Vol 38 (4) ◽  
pp. 967-972 ◽  
Author(s):  
Luc Buée ◽  
Laëtitia Troquier ◽  
Sylvie Burnouf ◽  
Karim Belarbi ◽  
Anneke Van der Jeugd ◽  
...  
Keyword(s):  
Cell Death ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorders ◽  
Neuronal Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Tau Proteins ◽  
Phosphorylated Tau ◽  
Sequence Of Events

Tau pathology is characterized by intracellular aggregates of abnormally and hyperphosphorylated tau proteins. It is encountered in many neurodegenerative disorders, but also in aging. These neurodegenerative disorders are referred to as tauopathies. Comparative biochemistry of the tau aggregates shows that they differ in both tau isoform phosphorylation and content, which enables a molecular classification of tauopathies. In conditions of dementia, NFD (neurofibrillary degeneration) severity is correlated to cognitive impairment and is often considered as neuronal death. Using tau animal models, analysis of the kinetics of tau phosphorylation, aggregation and neuronal death in parallel to electrophysiological and behavioural parameters indicates a disconnection between cognition deficits and neuronal cell death. Tau phosphorylation and aggregation are early events followed by cognitive impairment. Neuronal death is not observed before the oldest ages. A sequence of events may be the formation of toxic phosphorylated tau species, their aggregation, the formation of neurofibrillary tangles (from pre-tangles to ghost tangles) and finally neuronal cell death. This sequence will last from 15 to 25 years and one can ask whether the aggregation of toxic phosphorylated tau species is a protection against cell death. Apoptosis takes 24 h, but NFD lasts for 24 years to finally kill the neuron or rather to protect it for more than 20 years. Altogether, these data suggest that NFD is a transient state before neuronal death and that therapeutic interventions are possible at that stage.

scholarly journals Disruption of Bax Protein Prevents Neuronal Cell Death but Produces Cognitive Impairment in Mice following Traumatic Brain Injury

2008 ◽  
Vol 25 (7) ◽  
pp. 755-767 ◽  
Author(s):  
Roya Tehranian ◽  
Marie E. Rose ◽  
Vincent Vagni ◽  
Alicia M. Pickrell ◽  
Raymond P. Griffith ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Death ◽  
Cognitive Impairment ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Bax Protein

scholarly journals Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

2016 ◽  
Vol 371 (1700) ◽  
pp. 20150434 ◽  
Author(s):  
Michael J. Berridge
Keyword(s):  
Reactive Oxygen Species ◽  
Vitamin D ◽  
Neuronal Cell Death ◽  
Memory Loss ◽  
Neuronal Cell ◽  
Reactive Oxygen ◽  
Cardiac Cells ◽  
Amyloid Formation ◽  
Oxygen Species ◽  
Age Related

Vitamin D is a hormone that maintains healthy cells. It functions by regulating the low resting levels of cell signalling components such as Ca 2+ and reactive oxygen species (ROS). Its role in maintaining phenotypic stability of these signalling pathways depends on the ability of vitamin D to control the expression of those components that act to reduce the levels of both Ca 2+ and ROS. This regulatory role of vitamin D is supported by both Klotho and Nrf2. A decline in the vitamin D/Klotho/Nrf2 regulatory network may enhance the ageing process, and this is well illustrated by the age-related decline in cognition in rats that can be reversed by administering vitamin D. A deficiency in vitamin D has also been linked to two of the major diseases in man: heart disease and Alzheimer's disease (AD). In cardiac cells, this deficiency alters the Ca 2+ transients to activate the gene transcriptional events leading to cardiac hypertrophy and the failing heart. In the case of AD, it is argued that vitamin D deficiency results in the Ca 2+ landscape that initiates amyloid formation, which then elevates the resting level of Ca 2+ to drive the memory loss that progresses to neuronal cell death and dementia. This article is part of the themed issue ‘Evolution brings Ca 2+ and ATP together to control life and death’.

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 Recent updates on the role of herbal medicine for Alzheimer's disease (Dementia)

2021 ◽  
Vol 8 (1) ◽  
pp. 14-45
Author(s):  
Ravindra B. Malabadi ◽  
Kiran P. Kolkar ◽  
Neelambika T. Meti ◽  
Raju K. Chalannavar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Side Effects ◽  
Herbal Medicine ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Brain Disorder ◽  
Cognitive Changes ◽  
Potent Effect ◽  
Age Related

This review paper highlights the use of medicinal plants in the management of Alzheimer's disease and memory deficit. Alzheimer’s disease is the most common form of dementia, a serious brain disorder that impacts daily living through memory loss and cognitive changes. Alzheimer's disease is also age-related neurodegenerative disorders caused by progressive loss of structure or function of neurons, resulting in neuronal cell death. Alzheimer's patients have an acetylcholine deficiency. Stressful conditions, free radicle scavanging and oxidation are often associated with loss of memory and cognitive functions, which may lead to threats of schizophrenia and Alzheimer's disease. However, the use of allopathic drugs has resulted in the adverse side effects on the human body and thus limits the use of such drugs. Herbal cognitive enhancer drugs have shown their potent effect in Alzheimer’s disease due to their antioxidant and neuropharmacological actions. The use of natural cognitive enhancers evidenced to improve mental functions such as cognition, memory, intelligence, motivation, attention and concentration. Traditional Ayurvedic herbal system of medicine is fundamentally preventive, protective, nutritive, curative and less expensive. Therefore, the use of herbal medicine for the treatment of Alzheimer's disease is a novel approach without any side effects.

scholarly journals Optimized-SopungSunkiwon, a Herbal Formula, Attenuates AβOligomer-Induced Neurotoxicity in Alzheimer’s Disease Models

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jin Gyu Choi ◽  
Sun Yeou Kim ◽  
Jong Woo Kim ◽  
Myung Sook Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Medicinal Herbs ◽  
Glutathione Depletion ◽  
Age Related

Alzheimer’s disease (AD), the most common form of dementia, is an age-related neurodegenerative disease that is characterized by memory dysfunction, neuronal cell damage, and neuroinflammation. It is believed that AD-related pathology is mostly due to the overproduction of Aβ, especially the oligomeric form (AβO), in the brain. Evidence of the effects of multifunctional medicinal herbs in the treatment of AD has been steadily increasing. Optimized-SopungSunkiwon (OSS), a multiherbal formulation that is composed of six medicinal herbs derived from SopungSunkiwon, is a traditional medicine that is prescribed for neurodegenerative disorders in elderly patients. We previously reported that OSS showed an antiamnesic and memory enhancing effect in mice, but it is unknown whether OSS has a protective effect against AβO neurotoxicity. In this study, we investigated the effects of OSS in AD models induced by AβOin vitroandin vivo. We found that OSS protected neuronal cells and inhibited the generation of nitric oxide and reactive oxygen species against AβO toxicityin vitro. These results were confirmed byin vivodata that oral administration of OSS for 14 days attenuated memory impairments and neuronal cell death by modulating gliosis, glutathione depletion, and synaptic damage in the mouse hippocampus induced by AβO.

scholarly journals Deregulation of the Egfr/Ras Signaling Pathway Induces Age-related Brain Degeneration in the Drosophila Mutantvap

2003 ◽  
Vol 14 (1) ◽  
pp. 241-250 ◽  
Author(s):  
José A. Botella ◽  
Doris Kretzschmar ◽  
Claudia Kiermayer ◽  
Pascale Feldmann ◽  
David A. Hughes ◽  
...  
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Egf Receptor ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ras Signaling ◽  
Age Related ◽  
Receptor Signaling Pathway ◽  
Brain Degeneration

Ras signaling has been shown to play an important role in promoting cell survival in many different tissues. Here we show that upregulation of Ras activity in adult Drosophila neurons induces neuronal cell death, as evident from the phenotype of vacuolar peduncle (vap) mutants defective in theDrosophila RasGAP gene, which encodes a Ras GTPase-activating protein. These mutants show age-related brain degeneration that is dependent on activation of the EGF receptor signaling pathway in adult neurons, leading to autophagic cell death (cell death type 2). These results provide the first evidence for a requirement of Egf receptor activity in differentiated adultDrosophila neurons and show that a delicate balance of Ras activity is essential for the survival of adult neurons.

scholarly journals Minocycline Attenuates Neuronal Cell Death and Improves Cognitive Impairment in Alzheimer's Disease Models

2007 ◽  
Vol 32 (11) ◽  
pp. 2393-2404 ◽  
Author(s):  
Yoori Choi ◽  
Hye-Sun Kim ◽  
Ki Young Shin ◽  
Eun-Mee Kim ◽  
Minji Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Cognitive Impairment ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Disease Models

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.

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