scholarly journals Mahanimbine Improved Aging-Related Memory Deficits in Mice through Enhanced Cholinergic Transmission and Suppressed Oxidative Stress, Amyloid Levels, and Neuroinflammation

2021 ◽  
Vol 12 (1) ◽  
pp. 12
Author(s):  
Vasudevan Mani ◽  
Nur Syamimi Mohd Azahan ◽  
Kalavathy Ramasamy ◽  
Siong Meng Lim ◽  
Abu Bakar Abdul Majeed
Keyword(s):  
Oxidative Stress ◽  
Matched Control ◽  
Memory Deficits ◽  
Amyloid Formation ◽  
Memory Retention ◽  
Biochemical Tests ◽  
Aged Mice ◽  
Age Related ◽  
Cox 2 ◽  
Bace 1

Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), β-amyloid (Aβ1-40 and Aβ1-42), β-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Aβ1-40, and Aβ1-42, BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.

scholarly journals Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

2021 ◽  
Author(s):  
Sujeong Yang ◽  
Sylvain Gigout ◽  
Angelo Molinaro ◽  
Yuko Naito-Matsui ◽  
Sam Hilton ◽  
...  
Keyword(s):  
Chondroitin Sulphate ◽  
Memory Loss ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Aged Mice ◽  
Age Related ◽  
Term Potentiation ◽  
Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

scholarly journals Age-Dependent Oxidative Stress Elevates Arginase 1 and Uncoupled Nitric Oxide Synthesis in Skeletal Muscle of Aged Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chirayu D. Pandya ◽  
Byung Lee ◽  
Haroldo A. Toque ◽  
Bharati Mendhe ◽  
Robert T. Bragg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Cell Survival ◽  
Bone Fractures ◽  
Arginase Activity ◽  
Aged Mice ◽  
Arginase 1 ◽  
Age Related ◽  
Stress Dependent

Aging is associated with reduced muscle mass (sarcopenia) and poor bone quality (osteoporosis), which together increase the incidence of falls and bone fractures. It is widely appreciated that aging triggers systemic oxidative stress, which can impair myoblast cell survival and differentiation. We previously reported that arginase plays an important role in oxidative stress-dependent bone loss. We hypothesized that arginase activity is dysregulated with aging in muscles and may be involved in muscle pathophysiology. To investigate this, we analyzed arginase activity and its expression in skeletal muscles of young and aged mice. We found that arginase activity and arginase 1 expression were significantly elevated in aged muscles. We also demonstrated that SOD2, GPx1, and NOX2 increased with age in skeletal muscle. Most importantly, we also demonstrated elevated levels of peroxynitrite formation and uncoupling of eNOS in aged muscles. Our in vitro studies using C2C12 myoblasts showed that the oxidative stress treatment increased arginase activity, decreased cell survival, and increased apoptotic markers. These effects were reversed by treatment with an arginase inhibitor, 2(S)-amino-6-boronohexanoic acid (ABH). Our study provides strong evidence that L-arginine metabolism is altered in aged muscle and that arginase inhibition could be used as a novel therapeutic target for age-related muscle complications.

scholarly journals Comparative Analysis of Age-Related Changes in Lacrimal Glands and Meibomian Glands of a C57BL/6 Male Mouse Model

2020 ◽  
Vol 21 (11) ◽  
pp. 4169 ◽  
Author(s):  
Chang Ho Yoon ◽  
Jin Suk Ryu ◽  
Ho Sik Hwang ◽  
Mee Kum Kim
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Dependent Manner ◽  
Ki 67 ◽  
Aged Mice ◽  
Age Related ◽  
Ifn Γ ◽  
One Year ◽  
Corneal Staining ◽  
Old Mice

It is not known how biological changes in the lacrimal (LGs) and meibomian (MGs) glands contribute to dry eye disease (DED) in a time-dependent manner. In this study, we investigated time-sequenced changes in the inflammation, oxidative stress, and senescence of stem cells in both glands of an aging-related DED mouse model. Eight-week (8W)-, one-year (1Y)-, and two-year (2Y)-old C57BL/6 male mice were used. MG areas of the upper and lower eyelids were analyzed by transillumination meibography imaging. The number of CD45+, 8-OHdG+, Ki-67+, and BrdU+ cells was compared in both glands. Increased corneal staining and decreased tear secretion were observed in aged mice. The MG dropout area increased with aging, and the age-adjusted MG area in lower lids was negatively correlated with the National Eye Institute (NEI) score. Increased CD4+ interferon (IFN)-γ+ cells in LGs were found in both aged mice. An increase in 8-OHdG+ cells in both glands was evident in 2Y-old mice. Reduced Ki-67+ cells, but no change in CD45+ cells, was observed in the MGs of 1Y-old mice. Increased BrdU+ cells were observed in the LGs of aged mice. This suggests that age-dependent DED in C57BL/6 mice is related to inflammation of the LGs, the development of MG atrophy, and oxidative stress in both glands.

Hazelnut modulates neurobehaviour and ameliorates ageing-induced oxidative stress, and caspase-3-mediated apoptosis in mice

2020 ◽  
Vol 13 ◽  
Author(s):  
Anthony Tope Olofinnade ◽  
Adejoke Yetunde Onaolapo ◽  
Olakunle James Onaolapo ◽  
Olugbenga Adekunle Olowe
Keyword(s):  
Weight Gain ◽  
Caspase 3 ◽  
Standard Diet ◽  
Dopamine Level ◽  
Biochemical Tests ◽  
Aged Mice ◽  
Beneficial Effects ◽  
Body Tissues ◽  
Age Related ◽  
The Brain

Background: Organismal aging has been associated with deleterious effects in different body tissues and organs, including the brain. There have been reports from ancient medicinal scripts of the beneficial effects of nuts like hazelnut in preventing aging induced-brain atrophy and memory loss. Objectives: This study examined the potential beneficial effects of a diet supplemented with two different (Italian and Turkish) cultivars of hazelnut on the brain of aged mice. Methods: Aged (24 months old) mice were randomly assigned into 7 groups of ten mice each. Mice were grouped as standard diet (SD) control, three groups of Turkish and three groups of Italian hazelnut incorporated into SD at 2, 4 and 8% respectively. Animals were fed standard or hazelnut diet for 8 weeks. On day 56, behaviours in the elevated plus maze, radial-arm maze, open field, and Y-maze paradigms were monitored and scored, following which animals were euthanized. The brains were removed, weighed and homogenized for the assessment of specific biochemical tests. Result: Results showed that hazelnut-supplemented diet was associated with significantly increased weight gain, with the Italian hazelnut being associated with greater weight gain. Hazelnut-supplemented diet also increased behavioural parameters such as horizontal locomotion and grooming, while it decreased rearing activity. Working-memory also improved significantly with both cultivars of hazelnut, while anxiety indices were reduced at lower concentrations of Italian, and higher concentrations of Turkish hazelnut. Both hazelnut varieties were associated with reduction in acetylcholinesterase activity, reduction in superoxide dismutase activity, reduction in nitric oxide levels, reduction in caspase-3 level, but increased dopamine level. Conclusion: Overall hazelnut cultivars have beneficial effects on the brain in aged mice; suggesting a possible role in the prevention or management of age-related neurodegenerative changes.

Red wine extract protects against oxidative-stress-induced endothelial senescence

2012 ◽  
Vol 123 (8) ◽  
pp. 499-507 ◽  
Author(s):  
Ilse P. G. Botden ◽  
Hisko Oeseburg ◽  
Matej Durik ◽  
Frank P. J. Leijten ◽  
Leonie C. Van Vark-Van Der Zee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Red Wine ◽  
Umbilical Vein ◽  
Critical Role ◽  
Sirtuin 1 ◽  
Mrna Levels ◽  
Nitric Oxide Synthase Inhibitor ◽  
Age Related ◽  
Cox 2

Red wine polyphenols may preserve endothelial function during aging. Endothelial cell senescence enhances age-related endothelial dysfunction. We investigated whether RWE (red wine extract) prevents oxidative-stress-induced senescence in HUVECs (human umbilical-vein endothelial cells). Senescence was induced by exposing HUVECs to tBHP (t-butylhydroperoxide), and quantified by senescence-associated β-galactosidase staining. RWE (0–50 μg/ml) concentration dependently decreased senescence by maximally 33±7.1%. RWE prevented the senescence-associated increase in p21 protein expression, inhibited tBHP-induced DNA damage of endothelial cells and induced relaxation of PCAs (porcine coronary arteries). Inhibition of SIRT1 (sirtuin 1) by sirtinol partially reversed the effect of RWE on tBHP-induced senescence, whereas both the NOS (nitric oxide synthase) inhibitor L-NMMA (NG-monomethyl-L-arginine) and the COX (cyclo-oxygenase) inhibitor indomethacin fully inhibited it. Furthermore, incubation of HUVECs with RWE increased eNOS (endothelial NOS) and COX-2 mRNA levels as well as phosphorylation of eNOS at Ser1177. RWE protects endothelial cells from tBHP-induced senescence. NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE.

scholarly journals Divergence in the metabolome between natural aging and Alzheimer’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Holly C. Hunsberger ◽  
Bennett P. Greenwood ◽  
Vladimir Tolstikov ◽  
Niven R. Narain ◽  
Michael A. Kiebish ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Neurodegenerative Disorder ◽  
Memory Deficits ◽  
The United States ◽  
Contextual Fear Conditioning ◽  
System Level ◽  
Aged Mice ◽  
Age Related

Abstract Alzheimer’s disease (AD) is a progressive and debilitating neurodegenerative disorder and one of the leading causes of death in the United States. Although amyloid plaques and fibrillary tangles are hallmarks of AD, research suggests that pathology associated with AD often begins 20 or more years before symptoms appear. Therefore, it is essential to identify early-stage biomarkers in those at risk for AD and age-related cognitive decline (ARCD) in order to develop preventative treatments. Here, we used an untargeted metabolomics analysis to define system-level alterations following cognitive decline in aged and APP/PS1 (AD) mice. At 6, 12, and 24 months of age, both control (Ctrl) and AD mice were tested in a 3-shock contextual fear conditioning (CFC) paradigm to assess memory decline. AD mice exhibited memory deficits across age and these memory deficits were also seen in naturally aged mice. Prefrontal cortex (PFC), hippocampus (HPC), and spleen were then collected and analyzed for metabolomic alterations. A number of significant pathways were altered between Ctrl and AD mice and naturally aged mice. By identifying systems-level alterations following ARCD and AD, these data could provide insights into disease mechanisms and advance the development of biomarker panels.

scholarly journals Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 120-120
Author(s):  
Adam Nyul Toth ◽  
Tabea Wiedenhoeft ◽  
Stefano Tarantini ◽  
Tamas Csipo ◽  
Priya Balasubramanian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurovascular Unit ◽  
Neurovascular Coupling ◽  
Laser Speckle ◽  
Protective Effects ◽  
Contrast Imaging ◽  
Aged Mice ◽  
Cranial Window ◽  
Age Related

Abstract Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-related cognitive decline. Recently we developed a resveratrol (3,4′,5- trihydroxystilbene)-containing fusogenic liposome (FL-RSV)-based molecular delivery system that can effectively target cultured cerebromicrovascular endothelial cells, attenuating age-related oxidative stress. To assess the cerebromicrovascular protective effects of FL-RSV in vivo, aged (24-monthold) C57BL/6 mice were treated with FL-RSV for four days. To demonstrate effective cellular uptake of FL-RSV, accumulation of the lipophilic tracer dyes in cells of the neurovascular unit was confirmed using two-photon imaging (through a chronic cranial window). NVC was assessed by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. Treatment with FL-RSV significantly improved NVC responses by increasing NO-mediated vasodilation. These findings are paralleled by the protective effects of FL-RSV on endothelium-dependent relaxation in the aorta. Thus, treatment with FL-RSV rescues endothelial function and NVC responses in aged mice. We propose that resveratrol containing fusogenic liposomes could also be used for combined delivery of various anti-geronic factors, including proteins, small molecules, DNA vectors and mRNAs targeting key pathways involved in microvascular aging and neurovascular dysfunction for the prevention/treatment of age-related cerebromicrovascular pathologies and development of vascular cognitive impairment (VCI) in aging.

scholarly journals Loss of C/EBPδ Exacerbates Radiation-Induced Cognitive Decline in Aged Mice due to Impaired Oxidative Stress Response

2019 ◽  
Vol 20 (4) ◽  
pp. 885 ◽  
Author(s):  
Sudip Banerjee ◽  
Tyler Alexander ◽  
Debajyoti Majumdar ◽  
Thomas Groves ◽  
Frederico Kiffer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Short Term Memory ◽  
Atomic Bomb ◽  
Radiation Sensitivity ◽  
Neurocognitive Dysfunction ◽  
Aged Mice ◽  
Age Related ◽  
Increased Risk ◽  
Neurocognitive Decline

Aging is characterized by increased inflammation and deterioration of the cellular stress responses such as the oxidant/antioxidant equilibrium, DNA damage repair fidelity, and telomeric attrition. All these factors contribute to the increased radiation sensitivity in the elderly as shown by epidemiological studies of the Japanese atomic bomb survivors. There is a global increase in the aging population, who may be at increased risk of exposure to ionizing radiation (IR) as part of cancer therapy or accidental exposure. Therefore, it is critical to delineate the factors that exacerbate age-related radiation sensitivity and neurocognitive decline. The transcription factor CCAAT enhancer binding protein delta (C/EBPδ) is implicated with regulatory roles in neuroinflammation, learning, and memory, however its role in IR-induced neurocognitive decline and aging is not known. The purpose of this study was to delineate the role of C/EBPδ in IR-induced neurocognitive decline in aged mice. We report that aged Cebpd−/− mice exposed to acute IR exposure display impairment in short-term memory and spatial memory that correlated with significant alterations in the morphology of neurons in the dentate gyrus (DG) and CA1 apical and basal regions. There were no significant changes in the expression of inflammatory markers. However, the expression of superoxide dismutase 2 (SOD2) and catalase (CAT) were altered post-IR in the hippocampus of aged Cebpd−/− mice. These results suggest that Cebpd may protect from IR-induced neurocognitive dysfunction by suppressing oxidative stress in aged mice.

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