Lack of Autophagy Induction by Lithium Decreases Neuroprotective Effects in the Striatum of Aged Rats

The pharmacological modulation of autophagy is considered a promising neuroprotective strategy. While it has been postulated that lithium regulates this cellular process, the age-related effects have not been fully elucidated. Here, we evaluated lithium-mediated neuroprotective effects in young and aged striatum. After determining the optimal experimental conditions for inducing autophagy in loco with lithium carbonate (Li2CO3), we measured cell viability, reactive oxygen species (ROS) generation and oxygen consumption with rat brain striatal slices from young and aged animals. In the young striatum, Li2CO3 increased tissue viability and decreased ROS generation. These positive effects were accompanied by enhanced levels of LC3-II, LAMP 1, Ambra 1 and Beclin-1 expression. In the aged striatum, Li2CO3 reduced the autophagic flux and increased the basal oxygen consumption rate. Ultrastructural changes in the striatum of aged rats that consumed Li2CO3 for 30 days included electrondense mitochondria with disarranged cristae and reduced normal mitochondria and lysosomes area. Our data show that the striatum from younger animals benefits from lithium-mediated neuroprotection, while the striatum of older rats does not. These findings should be considered when developing neuroprotective strategies involving the induction of autophagy in aging.

Download Full-text

Neuroprotective Effects of Glochidion zeylanicum Leaf Extract against H2O2/Glutamate-Induced Toxicity in Cultured Neuronal Cells and Aβ-Induced Toxicity in Caenorhabditis elegans

Biology ◽

10.3390/biology10080800 ◽

2021 ◽

Vol 10 (8) ◽

pp. 800

Author(s):

Chatrawee Duangjan ◽

Panthakarn Rangsinth ◽

Shaoxiong Zhang ◽

Xiaojie Gu ◽

Michael Wink ◽

...

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Leaf Extract ◽

Neuronal Cells ◽

Antioxidant Properties ◽

Ros Generation ◽

Protective Effects ◽

Neuroprotective Effects ◽

Antioxidant Genes ◽

Age Related

Oxidative stress plays a crucial role in the development of age-related neurodegenerative diseases. Previously, Glochidion zeylanicum methanol (GZM) extract has been reported to have antioxidant and anti-aging properties. However, the effect of GZM on neuroprotection has not been reported yet; furthermore, the mechanism involved in its antioxidant properties remains unresolved. The study is aimed to demonstrate the neuroprotective properties of GZM extract and their underlying mechanisms in cultured neuronal (HT-22 and Neuro-2a) cells and Caenorhabditis elegans models. GZM extract exhibited protective effects against glutamate/H2O2-induced toxicity in cultured neuronal cells by suppressing the intracellular reactive oxygen species (ROS) generation and enhancing the expression of endogenous antioxidant enzymes (SODs, GPx, and GSTs). GZM extract also triggered the expression of SIRT1/Nrf2 proteins and mRNA transcription of antioxidant genes (NQO1, GCLM, and EAAT3) which are the master regulators of cellular defense against oxidative stress. Additionally, GZM extract exhibited protective effects to counteract β-amyloid (Aβ)-induced toxicity in C. elegans and promoted neuritogenesis properties in Neuro-2a cells. Our observations suggest that GZM leaf extract has interesting neuritogenesis and neuroprotective potential and can possibly act as potential contender for the treatment of oxidative stress-induced Alzheimer’s disease (AD) and related neurodegenerative conditions; however, this needs to be studied further in other in vivo systems.

Download Full-text

Neuroprotective Effects of losartan and Captopril in an H2O2- Induced Neurotoxicity Model of Neuro-2A Cells

10.21203/rs.3.rs-1150729/v1 ◽

2021 ◽

Author(s):

Negar Firouzabadi ◽

MohammadReza Kiafar ◽

Nahid Alimoradi ◽

Sara Keshtgar ◽

Fereshteh Mehdipour ◽

...

Keyword(s):

Cell Death ◽

Cell Viability ◽

Antihypertensive Drugs ◽

Cell Damage ◽

Mental Illnesses ◽

Ros Generation ◽

Sod Activity ◽

Neuroprotective Effects ◽

Positive Effects ◽

Intracellular Ca

Abstract Background: Depression is one of the most common mental illnesses and knowledge about its pathophysiology will assist in smart treatment of depression. RAS is a hormonal system that regulates blood pressure and fluid balance. Role of brain RAS has been highlighted in many mental and neurological disorders. Many drugs that target this system, such as ACEIs and ARBs, have shown positive effects on improving depression in clinical studies and animal models.Methods and results: Regarding the effectiveness RAS in depression, this study was conducted to compare the neuroprotective effects of ARB and ACEI drugs and common antidepressants on Neuro-2a cells. The cells were treated in the different concentrations of captopril, losartan, imipramine, and venlafaxine (1, 10, 50, 100 μM), after exposure to H2O2. Intracellular Ca2+ content, cell viability, SOD activity and ROS generation were measured in all groups. Our results show that cell viability of H2O2-treated cells was significantly increased in the presence of antihypertensive drugs. We observed a protective effect against ROS production in all drug groups in Neuro-2a cells. Losartan at all concentrations and captopril prevented cell damage caused by ROS. Cell death due to intracellular Ca2+, was significantly reduced with all antidepressant. At low concentrations of losartan and captopril cell death due to intracellular Ca2+was significantly reduced compared to the H2O2 group. Conclusions: Antihypertensive drugs, especially losartan can have neuroprotective effects and if approved in animal models, it may be used in the future as an adjunct in psychiatric diseases such as depression.

Download Full-text

Activity Engagement in Cognitive Aging: A Review of the Evidence

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld23.1.35 ◽

2013 ◽

Vol 23 (1) ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Yvonne Rogalski ◽

Muriel Quintana

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Cognitive Aging ◽

Social Activity ◽

Current Evidence ◽

Omega 3 ◽

Neuroprotective Effects ◽

Activity Engagement ◽

Age Related ◽

Age Related Cognitive Decline

The population of older adults is rapidly increasing, as is the number and type of products and interventions proposed to prevent or reduce the risk of age-related cognitive decline. Advocacy and prevention are part of the American Speech-Language-Hearing Association’s (ASHA’s) scope of practice documents, and speech-language pathologists must have basic awareness of the evidence contributing to healthy cognitive aging. In this article, we provide a brief overview outlining the evidence on activity engagement and its effects on cognition in older adults. We explore the current evidence around the activities of eating and drinking with a discussion on the potential benefits of omega-3 fatty acids, polyphenols, alcohol, and coffee. We investigate the evidence on the hypothesized neuroprotective effects of social activity, the evidence on computerized cognitive training, and the emerging behavioral and neuroimaging evidence on physical activity. We conclude that actively aging using a combination of several strategies may be our best line of defense against cognitive decline.

Download Full-text

Calycosin-7-O-β-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells

Neural Plasticity ◽

10.1155/2019/8798069 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Xiangli Yan ◽

Aiming Yu ◽

Haozhen Zheng ◽

Shengxin Wang ◽

Yingying He ◽

...

Keyword(s):

Oxidative Stress ◽

Neuronal Apoptosis ◽

Ischemia Reperfusion ◽

Glucose Deprivation ◽

Pathological Process ◽

Neuroprotective Effects ◽

Ht22 Cells ◽

Positive Effects ◽

Antioxidant Stress

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-β-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

Download Full-text

Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22073604 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3604

Author(s):

Nicola Alessio ◽

Carmela Belardo ◽

Maria Consiglia Trotta ◽

Salvatore Paino ◽

Serena Boccella ◽

...

Keyword(s):

Spinal Cord ◽

Vitamin D ◽

Chronic Pain ◽

Vitamin D Deficiency ◽

Morphological Analysis ◽

Pain Perception ◽

Ex Vivo ◽

Ros Generation ◽

Peroxisome Proliferator ◽

Neuroprotective Effects

The bioactive form of vitamin .D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.

Download Full-text

Dendranthema zawadskii var. lucidum (Nakai) J.H. Park Extract Inhibits Cellular Senescence in Human Dermal Fibroblasts and Aging-Related Inflammation in Rats

Processes ◽

10.3390/pr9050801 ◽

2021 ◽

Vol 9 (5) ◽

pp. 801

Author(s):

Jehun Choi ◽

Gwi-Yeong Jang ◽

Jeonghoon Lee ◽

Hae-Young Chung ◽

Hyung-Jun Noh ◽

...

Keyword(s):

Cellular Senescence ◽

Cell Cycle Progression ◽

Inflammatory Responses ◽

Dermal Fibroblast ◽

Dermal Fibroblasts ◽

Dependent Manner ◽

Aged Rats ◽

Age Related ◽

Dendranthema Zawadskii ◽

Beta Galactosidase

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.

Download Full-text

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology

Life ◽

10.3390/life11030242 ◽

2021 ◽

Vol 11 (3) ◽

pp. 242

Author(s):

Salvatore Nesci ◽

Fabiana Trombetti ◽

Alessandra Pagliarani ◽

Vittoria Ventrella ◽

Cristina Algieri ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Atp Synthase ◽

Mitochondrial Permeability Transition ◽

Ros Generation ◽

Protonmotive Force ◽

Mitochondrial Oxidative Phosphorylation ◽

F1fo Atp Synthase ◽

Functional Changes ◽

Age Related ◽

Mitochondrial Functions

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

Download Full-text

A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy

Nutrients ◽

10.3390/nu13072441 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2441

Author(s):

Drake W. Lem ◽

Dennis L. Gierhart ◽

Pinakin Gunvant Davey

Keyword(s):

Diabetic Retinopathy ◽

Vision Loss ◽

Therapeutic Potential ◽

Microvascular Disease ◽

Age Related Macular Degeneration ◽

Cell Degeneration ◽

Neuroprotective Effects ◽

Age Related ◽

Induced Changes ◽

Dietary Carotenoid

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

Download Full-text

Metabolism during normoxia, hyperoxia, and recovery in newborn rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-051 ◽

1992 ◽

Vol 70 (3) ◽

pp. 408-411 ◽

Cited By ~ 20

Author(s):

Peter B. Frappell ◽

Andrea Dotta ◽

Jacopo P. Mortola

Keyword(s):

Carbon Dioxide ◽

Oxygen Consumption ◽

Metabolic Rate ◽

Carbon Dioxide Production ◽

Oxygen Availability ◽

Aerobic Metabolism ◽

Newborn Rats ◽

Ambient Temperatures ◽

Positive Effects

Aerobic metabolism (oxygen consumption, [Formula: see text], and carbon dioxide production, [Formula: see text]) has been measured in newborn rats at 2 days of age during normoxia, 30 min of hyperoxia (100% O2) and an additional 30 min of recovery in normoxia at ambient temperatures of 35 °C (thermoneutrality) or 30 °C. In normoxia, at 30 °C [Formula: see text] was higher than at 35 °C. With hyperoxia, [Formula: see text] increased in all cases, but more so at 30 °C (+20%) than at 35 °C (+9%). Upon return to normoxia, metabolism readily returned to the prehyperoxic value. The results support the concept that the normoxic metabolic rate of the newborn can be limited by the availability of oxygen. At temperatures below thermoneutrality the higher metabolic needs aggravate the limitation in oxygen availability, and the positive effects of hyperoxia on [Formula: see text] are therefore more apparent.Key words: neonatal respiration, oxygen consumption, thermoregulation.

Download Full-text

Physical activity in elderly

European Journal of Translational Myology ◽

10.4081/ejtm.2015.5280 ◽

2015 ◽

Vol 25 (4) ◽

pp. 249 ◽

Cited By ~ 21

Author(s):

Jan Cvecka ◽

Veronika Tirpakova ◽

Milan Sedliak ◽

Helmut Kern ◽

Winfried Mayr ◽

...

Keyword(s):

Physical Activity ◽

Electrical Stimulation ◽

Muscle Mass ◽

Irreversible Process ◽

Significant Decline ◽

Positive Effects ◽

Age Related ◽

And Performance ◽

And Function ◽

Age Related Changes

Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared.

Download Full-text