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 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.

scholarly journals Inhibition of NADPH Oxidase Activation by Apocynin Rescues Seizure-Induced Reduction of Adult Hippocampal Neurogenesis

2018 ◽  
Vol 19 (10) ◽  
pp. 3087 ◽  
Author(s):  
Song Lee ◽  
Bo Choi ◽  
A Kho ◽  
Jeong Jeong ◽  
Dae Hong ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neuronal Survival ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Oxidative Injury ◽  
Term Treatment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Nuclear Antigen ◽  
Long Term Treatment

Apocynin, also known as acetovanillone, is a natural organic compound structurally related to vanillin. Apocynin is known to be an inhibitor of NADPH (Nicotinamide adenine dinucleotide phosphate) oxidase activity and is highly effective in suppressing the production of superoxide. The neuroprotective effects of apocynin have been investigated in numerous brain injury settings, such as stroke, traumatic brain injury (TBI), and epilepsy. Our lab has demonstrated that TBI or seizure-induced oxidative injury and neuronal death were reduced by apocynin treatment. Several studies have also demonstrated that neuroblast production is transiently increased in the hippocampus after seizures. Here, we provide evidence confirming the hypothesis that long-term treatment with apocynin may enhance newly generated hippocampal neuronal survival by reduction of superoxide production after seizures. A seizure was induced by pilocarpine [(25 mg/kg intraperitoneal (i.p.)] injection. Apocynin was continuously injected for 4 weeks after seizures (once per day) into the intraperitoneal space. We evaluated neuronal nuclear antigen (NeuN), bromodeoxyuridine (BrdU), and doublecortin (DCX) immunostaining to determine whether treatment with apocynin increased neuronal survival and neurogenesis in the hippocampus after seizures. The present study indicates that long-term treatment of apocynin increased the number of NeuN+ and DCX+ cells in the hippocampus after seizures. Therefore, this study suggests that apocynin treatment increased neuronal survival and neuroblast production by reduction of hippocampal oxidative injury after seizures.

scholarly journals Epigenetic rejuvenation of the hippocampus by environmental enrichment

2019 ◽  
Author(s):  
Sara Zocher ◽  
Rupert W. Overall ◽  
Mathias Lesche ◽  
Andreas Dahl ◽  
Gerd Kempermann
Keyword(s):  
Dna Methylation ◽  
Brain Function ◽  
Environmental Enrichment ◽  
Brain Aging ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Lifestyle Interventions ◽  
Epigenetic Changes ◽  
Aging Effects ◽  
Age Related

AbstractThe decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that environmental enrichment counteracted age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is known to control neuronal functions. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the rejuvenating effects of environmental enrichment at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.

Potential Role of Adult Hippocampal Neurogenesis in Traumatic Brain Injury

2021 ◽  
Vol 28 ◽  
Author(s):  
Lucas Alexandre Santos Marzano ◽  
Fabyolla Lúcia Macedo de Castro ◽  
Caroline Amaral Machado ◽  
João Luís Vieira Monteiro de Barros ◽  
Thiago Macedo e Cordeiro ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Hippocampal Neurogenesis ◽  
Cognitive Outcomes ◽  
Adult Hippocampal Neurogenesis ◽  
The Brain

: Traumatic brain injury (TBI) is a serious cause of disability and death among young and adult individuals, displaying complex pathophysiology including cellular and molecular mechanisms that are not fully elucidated. Many experimental and clinical studies investigated the potential relationship between TBI and the process by which neurons are formed in the brain, known as neurogenesis. Currently, there are no available treatments for TBI’s long-term consequences being the search for novel therapeutic targets, a goal of highest scientific and clinical priority. Some studies evaluated the benefits of treatments aimed at improving neurogenesis in TBI. In this scenario, herein, we reviewed current pre-clinical studies that evaluated different approaches to improving neurogenesis after TBI while achieving better cognitive outcomes, which may consist in interesting approaches for future treatments.

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.

Estrogenic Regulation of Hippocampal Neurogenesis Throughout the Lifespan

2020 ◽  
pp. 253-281
Author(s):  
Shunya Yagi ◽  
Rand S. Eid ◽  
Wansu Qiu ◽  
Paula Duarte-Guterman ◽  
Liisa A. M. Galea
Keyword(s):  
Steroid Hormones ◽  
Cognitive Training ◽  
Adult Female ◽  
Ovarian Hormones ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Maternal Experience ◽  
Number Of Factors ◽  
Estrogenic Regulation

Neurogenesis in the hippocampus exists across a number of species, including humans. Steroid hormones, such as estrogens, modulate neurogenesis dependent on age, reproductive experience and sex. Findings are discussed in the chapter with reference to how neurogenesis in the hippocampus is related to learning and memory. Natural fluctuations in ovarian hormones or removal of ovaries modulate neurogenesis in the short term but not in the long term. Maternal experience has long-lasting effects on neurogenesis in the hippocampus. Acute estrogens increase proliferation in adult female rodents, but influence survival of new neurons dependent on a number of factors including sex, cognitive training, type of estrogen, and whether or not cells were produced under estrogens. This chapter outlines findings indicating that estrogens can be strong modulators of adult hippocampal neurogenesis, which may have implications for disorders involving hippocampal dysfunction that target women.

scholarly journals Acute and Fractionated Exposure to High-LET56Fe HZE-Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis

2013 ◽  
Vol 180 (6) ◽  
pp. 658-667 ◽  
Author(s):  
Phillip D. Rivera ◽  
Hung-Ying Shih ◽  
Junie A. LeBlanc ◽  
Mara G. Cole ◽  
Wellington Z. Amaral ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Particle Radiation

scholarly journals Correction: Long-Term Mild, rather than Intense, Exercise Enhances Adult Hippocampal Neurogenesis and Greatly Changes the Transcriptomic Profile of the Hippocampus

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133089 ◽  
Author(s):  
Koshiro Inoue ◽  
Masahiro Okamoto ◽  
Junko Shibato ◽  
Min Chul Lee ◽  
Takashi Matsui ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Intense Exercise ◽  
Transcriptomic Profile

scholarly journals The pharmacological stimulation of Nurr1 improves cognitive functions via enhancement of adult hippocampal neurogenesis

2016 ◽  
Vol 17 (3) ◽  
pp. 534-543 ◽  
Author(s):  
Jin-il Kim ◽  
Seong Gak Jeon ◽  
Kyoung Ah Kim ◽  
Yong Jun Kim ◽  
Eun Ji Song ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pharmacological Stimulation ◽  
Stimulation Of
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