scholarly journals Ascorbic Acid Mitigates D-galactose-Induced Brain Aging by Increasing Hippocampal Neurogenesis and Improving Memory Function

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 176 ◽  
Author(s):  
Sung Nam ◽  
Misun Seo ◽  
Jin-Seok Seo ◽  
Hyewhon Rhim ◽  
Sang-Soep Nahm ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Cellular Proliferation ◽  
Brain Aging ◽  
Memory Function ◽  
Interleukin 1 ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Normal Brain ◽  
Long Term Treatment

Ascorbic acid is essential for normal brain development and homeostasis. However, the effect of ascorbic acid on adult brain aging has not been determined. Long-term treatment with high levels of D-galactose (D-gal) induces brain aging by accumulated oxidative stress. In the present study, mice were subcutaneously administered with D-gal (150 mg/kg/day) for 10 weeks; from the seventh week, ascorbic acid (150 mg/kg/day) was orally co-administered for four weeks. Although D-gal administration alone reduced hippocampal neurogenesis and cognitive functions, co-treatment of ascorbic acid with D-gal effectively prevented D-gal-induced reduced hippocampal neurogenesis through improved cellular proliferation, neuronal differentiation, and neuronal maturation. Long-term D-gal treatment also reduced expression levels of synaptic plasticity-related markers, i.e., synaptophysin and phosphorylated Ca2+/calmodulin-dependent protein kinase II, while ascorbic acid prevented the reduction in the hippocampus. Furthermore, ascorbic acid ameliorated D-gal-induced downregulation of superoxide dismutase 1 and 2, sirtuin1, caveolin-1, and brain-derived neurotrophic factor and upregulation of interleukin 1 beta and tumor necrosis factor alpha in the hippocampus. Ascorbic acid-mediated hippocampal restoration from D-gal-induced impairment was associated with an enhanced hippocampus-dependent memory function. Therefore, ascorbic acid ameliorates D-gal-induced impairments through anti-oxidative and anti-inflammatory effects, and it could be an effective dietary supplement against adult brain aging.

Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions

Gerontology ◽  
2018 ◽  
Vol 64 (6) ◽  
pp. 562-575 ◽  
Author(s):  
Sung Min Nam ◽  
Hongik Hwang ◽  
Misun Seo ◽  
Byung-Joon Chang ◽  
Hyeon-Joong Kim ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Brain Aging ◽  
Hippocampal Neurogenesis ◽  
Receptor Expression ◽  
Adult Hippocampal Neurogenesis ◽  
Aging Effects ◽  
Memory Dysfunction ◽  
Long Term Treatment ◽  
Lpa1 Receptor

Background: Ginseng has been used to improve brain function and increase longevity. However, little is known about the ingredients of ginseng and molecular mechanisms of its anti-brain aging effects. Gintonin is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand; LPA and LPA1 receptors are involved in adult hippocampal neurogenesis. D-galactose (D-gal) is used to induce brain ­aging in animal models because long-term treatment with D-gal facilitates hippocampal aging in experimental adult animals by decreasing hippocampal neurogenesis and inducing learning and memory dysfunction. Objective: To investigate the protective effects of gintonin on D-gal-induced hippocampal senescence, impairment of long-term potentiation (LTP), and memory dysfunction. Methods: Brain hippocampal aging was induced by D-gal administration (150 mg/kg/day, s.c.; 10 weeks). From the 7th week, gintonin (50 or 100 mg/kg/day, per os) was co-administered with D-gal for 4 weeks. We performed histological analyses, LTP measurements, and object location test. Results:  Co-administration of gintonin ameliorated D-gal-induced reductions in hippocampal Ki67-immunoreactive proliferating cells, doublecortin-immunoreactive neuroblasts, 5-bromo-2’-deoxyuridine-incorporating NeuN-immunoreactive mature neurons, and LPA1 receptor expression. Co-administration of gintonin in D-gal-treated mice increased the expression of phosphorylated cyclic adenosine monophosphate response element binding protein in the hippocampal dentate gyrus. In addition, co-administration of gintonin in D-gal-treated mice enhanced LTP and restored the cognitive functions compared with those in mice treated with D-gal only. Conclusion: These results show that gintonin administration restores D-gal-induced memory deficits by enhancing hippocampal LPA1 receptor expression, LTP, and neurogenesis. Finally, the present study shows that gintonin exerts anti-brain aging effects that are responsible for alleviating brain aging-related dysfunction.

scholarly journals Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariano Guardia Clausi ◽  
Alexander M. Stessin ◽  
Zirun Zhao ◽  
Stella E. Tsirka ◽  
Samuel Ryu
Keyword(s):  
Brain Tissue ◽  
Cranial Irradiation ◽  
Subcortical White Matter ◽  
Glioma Cell Line ◽  
Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Long Term Effects ◽  
Normal Brain Tissue ◽  
Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

scholarly journals Effects of Long-Term Treatment with a Blend of Highly Purified Olive Secoiridoids on Cognition and Brain ATP Levels in Aged NMRI Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Martina Reutzel ◽  
Rekha Grewal ◽  
Carmina Silaidos ◽  
Jens Zotzel ◽  
Stefan Marx ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Citrate Synthase ◽  
Brain Aging ◽  
Mrna Levels ◽  
Nmri Mice ◽  
Aged Mice ◽  
Atp Levels ◽  
Long Term Treatment ◽  
The Brain

Aging represents a major risk factor for developing neurodegenerative diseases such as Alzheimer’s disease (AD). As components of the Mediterranean diet, olive polyphenols may play a crucial role in the prevention of AD. Since mitochondrial dysfunction acts as a final pathway in both brain aging and AD, respectively, the effects of a mixture of highly purified olive secoiridoids were tested on cognition and ATP levels in a commonly used mouse model for brain aging. Over 6 months, female NMRI mice (12 months of age) were fed with a blend containing highly purified olive secoiridoids (POS) including oleuropein, hydroxytyrosol and oleurosid standardized for 50 mg oleuropein/kg diet (equivalent to 13.75 mg POS/kg b.w.) or the study diet without POS as control. Mice aged 3 months served as young controls. Behavioral tests showed deficits in cognition in aged mice. Levels of ATP and mRNA levels of NADH-reductase, cytochrome-c-oxidase, and citrate synthase were significantly reduced in the brains of aged mice indicating mitochondrial dysfunction. Moreover, gene expression of Sirt1, CREB, Gap43, and GPx-1 was significantly reduced in the brain tissue of aged mice. POS-fed mice showed improved spatial working memory. Furthermore, POS restored brain ATP levels in aged mice which were significantly increased. Our results show that a diet rich in purified olive polyphenols has positive long-term effects on cognition and energy metabolism in the brain of aged mice.

scholarly journals Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

2017 ◽  
Vol 114 (17) ◽  
pp. E3536-E3545 ◽  
Author(s):  
Qianfa Long ◽  
Dinesh Upadhya ◽  
Bharathi Hattiangady ◽  
Dong-Ki Kim ◽  
Su Yeon An ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Memory Function ◽  
Hippocampal Neurogenesis ◽  
Medical Emergency ◽  
Memory Impairments ◽  
Functional Deficits ◽  
Persistent Inflammation ◽  
Antiepileptic Drug Treatment ◽  
Antiinflammatory Effects

Status epilepticus (SE), a medical emergency that is typically terminated through antiepileptic drug treatment, leads to hippocampus dysfunction typified by neurodegeneration, inflammation, altered neurogenesis, as well as cognitive and memory deficits. Here, we examined the effects of intranasal (IN) administration of extracellular vesicles (EVs) secreted from human bone marrow-derived mesenchymal stem cells (MSCs) on SE-induced adverse changes. The EVs used in this study are referred to as A1-exosomes because of their robust antiinflammatory properties. We subjected young mice to pilocarpine-induced SE for 2 h and then administered A1-exosomes or vehicle IN twice over 24 h. The A1-exosomes reached the hippocampus within 6 h of administration, and animals receiving them exhibited diminished loss of glutamatergic and GABAergic neurons and greatly reduced inflammation in the hippocampus. Moreover, the neuroprotective and antiinflammatory effects of A1-exosomes were coupled with long-term preservation of normal hippocampal neurogenesis and cognitive and memory function, in contrast to waned and abnormal neurogenesis, persistent inflammation, and functional deficits in animals receiving vehicle. These results provide evidence that IN administration of A1-exosomes is efficient for minimizing the adverse effects of SE in the hippocampus and preventing SE-induced cognitive and memory impairments.

P2-257: Long-term effects of simvastatin and atorvastatin on a rat model of normal brain aging

2009 ◽  
Vol 5 (4S_Part_11) ◽  
pp. P335-P335
Author(s):  
James L. Searcy ◽  
Caitlin S. Latimer ◽  
Olivier Thibault ◽  
Eric M. Blalock ◽  
Kuey-Chu Chen ◽  
...  
Keyword(s):  
Rat Model ◽  
Brain Aging ◽  
Normal Brain ◽  
Long Term Effects

scholarly journals Vitamin C In Neuropsychiatry

2015 ◽  
Vol 16 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Dragan M. Pavlović ◽  
Merdin Š. Markišić ◽  
Aleksandra M. Pavlović
Keyword(s):  
Ascorbic Acid ◽  
Vitamin C ◽  
The Body ◽  
Adult Brain ◽  
Normal Brain ◽  
Positive Effects ◽  
Normal Brain Function ◽  
High Concentrations ◽  
High Doses ◽  
The Brain

Abstract Vitamins are necessary factors in human development and normal brain function. Vitamin C is a hydrosoluble compound that humans cannot produce; therefore, we are completely dependent on food intake for vitamin C. Ascorbic acid is an important antioxidative agent and is present in high concentrations in neurons and is also crucial for collagen synthesis throughout the body. Ascorbic acid has a role in modulating many essential neurotransmitters, enables neurogenesis in adult brain and protects cells against infection. While SVCT1 enables the absorption of vitamin C in the intestine, SVCT2 is primarily located in the brain. Ascorbate deficiency is classically expressed as scurvy, which is lethal if not treated. However, subclinical deficiencies are probably much more frequent. Potential fields of vitamin C therapy are in neurodegenerative, cerebrovascular and affective diseases, cancer, brain trauma and others. For example, there is some data on its positive effects in Alzheimer’s disease. Various dosing regimes are used, but ascorbate is safe, even in high doses for protracted periods. Better designed studies are needed to elucidate all of the potential therapeutic roles of vitamin C.

scholarly journals A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Odette Leiter ◽  
Gerd Kempermann ◽  
Tara L. Walker
Keyword(s):  
Immune System ◽  
Adult Neurogenesis ◽  
Immune Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Intrinsic Cues ◽  
Normal Brain Function ◽  
The Brain

Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus—a region crucial for learning and memory.

scholarly journals Long-term Treatment with Olanzapine Increases the Number of Sox2 and Doublecortin Expressing Cells in the Adult Subventricular Zone

2018 ◽  
Vol 17 (6) ◽  
pp. 458-463 ◽  
Author(s):  
Barbara Lasut ◽  
Artur Palasz ◽  
Lukasz Filipczyk ◽  
Oscar Arias-Carrion ◽  
Ewa Rojczyk ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Cell Formation ◽  
Term Treatment ◽  
Adult Brain ◽  
Mood Stabilizers ◽  
Fluorescent Detection ◽  
Subgranular Zone ◽  
Adult Rat ◽  
Long Term Treatment

Background & Objective: Continuously active neurogenic regions in the adult brain are located in the subventricular zone (SVZ) of the lateral ventricles and subgranular zone of the hippocampal dentate gyrus. Neurogenesis is modulated by many factors such as growth factors, neurotransmitters and hormones. Neuropsychiatric drugs, especially antidepressants, mood stabilizers and antipsychotics may also affect the origin of neuronal cells. Method: The purpose of this study was to determine the effects of chronic olanzapine treatment on adult rat neurogenesis at the level of the SVZ. The number of neuroblasts was evaluated using immunohistochemical and fluorescent detection of sex determining region Y-box 2 and doublecortin expressing cells. Results & Conclusion: The results indicate that olanzapine has proneurogenic effects on the adult rat SVZ, as the mean number of sex determining region Y-box 2 and doublecortin-positive cells increased significantly, while there was a similar tendency in the subgranular zone. Collectively, these results suggest that long-term treatment with olanzapine may stimulate neurogenic stem cell formation in the SVZ which supports adult neurogenesis.

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