• 운동영양학회지
• /
• 제23권3호
• /
• pp.13-21
• /
• 2019

[Purpose] Chronic stress is a precipitating factor for depression, whereas exercise is beneficial for both the mood and cognitive process. The current study demonstrates the anti-depressive effects of regular exercise and the mechanisms linked to hippocampal neurogenesis. [Methods] Mice were subjected to 14 consecutive days of restraint, followed by 3 weeks of treadmill running, and were then subjected to behavioral tests that included the forced swimming and Y-maze tests. Protein levels were assessed using western blot analysis and newborn cells were detected using 5-bromo-2'-deoxyuridine (BrdU). [Results] Three weeks of treadmill running ameliorated the behavioral depression caused by 14 days of continuous restraint stress. The exercise regimen enhanced BrdU-labeled cells and class III β-tubulin levels in the hippocampal dentate gyrus, as well as those of thioredoxin-1 (TRX-1) and synaptosomal β2-adrenergic receptors (β2-AR) under stress. In vitro experiments involving treatment with recombinant human TRX-1 (rhTRX-1) augmented the levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear β-catenin, and proliferating cell nuclear antigens, which were previously inhibited by U0216 and FH535 (inhibitors of ERK1/2 and β-catenin/T cell factor-mediated transcription, respectively). The hippocampal neurogenesis elicited by a 7-day exercise regimen was abolished by a selective inhibitor of β2-AR, butoxamine. [Conclusion] These results suggest that TRX-1-mediated hippocampal neurogenesis by β2-AR function is a potential mechanism underlying the psychotropic effect of exercise.

• Molecules and Cells
• /
• 제39권8호
• /
• pp.603-610
• /
• 2016

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.

• Journal of Ginseng Research
• /
• 제33권2호
• /
• pp.132-138
• /
• 2009

Previous studies suggest that even low-dose irradiation can lead to progressive cognitive decline and memory deficits, which implicates, in part, hippocampal dysfunction in both humans and experimental animals. In this study, whether red ginseng (RG) could attenuate memory impairment was investigated through a passive-avoidance and object recognition memory test, as well as the suppression of hippocampal neurogenesis, using the TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) in adult mice treated with a relatively low-dose exposure to gamma radiation (0.5 or 2.0 Gy). RG was administered intraperitonially at a dosage of 50 mg/kg of body weight, at 36 and 12 h pre-irradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg! kg of body weight/day for seven days before autopsy. In the passive-avoidance and object recognition memory test, the mice that were trained for one day after acute irradiation (2 Gy) showed significant memory deficits compared with the sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 12 h after irradiation. In addition, the number of Ki-67- and DCX-positive cells was significantly decreased. RG treatment prior to irradiation attenuated the memory defect and blocked apoptotic death as well as a decrease in the Ki-67- and DCX-positive cells. RG may attenuate memory defect in a relatively low-dose exposure to radiation in adult mice, possibly by inhibiting the detrimental effect of irradiation on hippocampal neurogenesis.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권1호
• /
• pp.41-51
• /
• 2016

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activating TLR4-NF-${\kappa}B$ signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-${\kappa}B$ pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPS-induced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.

• BMB Reports
• /
• 제44권6호
• /
• pp.421-421
• /
• 2011

• International Journal of Oral Biology
• /
• 제33권2호
• /
• pp.59-64
• /
• 2008

This study was designed to investigate the changes in the properties of the neuronal setm cells or progenitor cells associated with age-related decline in neurogenesis of the hippocampal dentate gyrus (DG). Active whole cells cycle marker Ki67 (a marker of whole cell cycle)-positive and S phase marker bromodeoxyuridine (BrdU)-positive. Neural stem cells gradually were reduced in the hippocampal subgranular zone (SGZ) in an age-dependant manner after birth (from P1 month to P1 year). The ratio of BrdUpositivecells/Ki67-positive cells was gradually enhanced in an age-dependent manner. The ratio of Ki67-positive cells/accu-mulating BrdU-positive cells at 3 hrs after BrdU injection was injected once a day for consecutive 5 days gradually decreased during ageing. TUNEL- and caspase 3 (apoptotic terminal caspase)-positive cells gradually decreased in the dentate SGZ during ageing and immunohistochemical findings of glial fibrillary acid protein (GFAP) were not changed during ageing. NeuN, a marker of mature neural cells, and BrdU-double positive cells gradually decreased in an age-dependent manner but differentiating ratio and survival rate of cells were not changed at 4 wks after BrdU injection once a day for consecutive 5 days. The number of BrdU-positive cells migrated from the hippocampal SGZ into granular layer and its migration speed was gradually declined during ageing. These results suggest that the adult neurogenesis in the mouse hippocampal DG gradually decrease through reducing proliferation of neural stem cells accompanying with cells cycle change and reduced cells migration rather than changes of differentiation.

• 대한한의학회지
• /
• 제38권2호
• /
• pp.31-40
• /
• 2017

Objectives: We investigated the effect of acupuncture on memory function in relation with neurogenesis in old rats. Methods: In this study, a step-down avoidance task for short-term memory and Y-maze task for spatial memory capability were conducted. Western blot analysis for brain-derived neurotorphic factor (BDNF) and tyrosine kinase B (TrkB), and immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) were performed. Results: Short-term memory and spatial memories were decreased in the old-aged rats. Expressions of BDNF and TrkB in the hippocampus were significantly decreased in the old-aged rats. Neurogenesis in the hippocampal dentate gyrus was also decreased in the old-aged rats. However, acupuncture treatment alleviated impairment of short-term and spatial memories induced by ageing. Acupuncture also increased the expressions of BDNF and TrkB and enhanced neurogenesis in the hippocampus. The present study showed that acupuncture alleviated ageing-induced short-term and spatial memory loss by increasing of BDNF and neurogenesis. Acupuncture at ST41-acupoint showed most potent effect than at ST36-acupoint or non-acupoint. Conclusions: Acupuncture might be used as the effective therapeutic modality to ameliorate the age-related decrease of brain functions.

• Journal of Radiation Protection and Research
• /
• 제37권3호
• /
• pp.123-128
• /
• 2012

방사선 노출은 해마 기능이상으로 인한 인지장애와 기억력 감퇴가 나타난다. 본 연구에서는 마우스에 방사선 노출(감마선 0.5 또는 2 Gy) 후 passive avoidance 및 object recognition test를 적용한 행동이상, apoptosis 측정 및 신경발생 관찰지표로서 Kiel 67 (Ki-67) 및 doublecortin (DCX)에 대한 면역염색 방법을 적용하여 diethyldithiocarbamate(DDC)의 학습기억 장애 경감효과를 관찰하였다. DDC는 방사선 조사 30분 전에 1회(체중 kg당 1,000 mg) 복강 내 주사하였다. Passive avoidance 및 object recognition test 결과, 정상대조군에 비해 방사선 단독조사군(2 Gy)에서 유의성 있는 학습기억 장애를 나타냈으며, 방사선 조사 후 12시간에 치아이랑 부위의 apoptosis 발생세포의 수가 증가하였고, Ki-67 및 DCX 양성세포의 수는 현저히 감소하였다. 방사선 노출 전 DDC 처리군에서는 유의성 있는 행동장애 완화, apoptosis 발생 감소가 관찰되었고, 평균치를 기준으로 Ki-67 및 DCX 양성세포의 수도 약간 증가하였다. DDC는 성숙마우스에서 방사선에 의한 해마 신경세포발생 및 학습기억 장애 개선효과가 있는 것으로 사료된다.

• Biomolecules & Therapeutics
• /
• 제21권3호
• /
• pp.229-233
• /
• 2013

This study was aimed at investigating the possible effects of phytoceramide (Pcer) on learning and memory and their underlying mechanisms. Phytoceramide was orally administered to ICR mice for 7 days. Memory performances were assessed using the passive avoidance test and Y-maze task. The expressions of phosphorylated cAMP response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF) were measured with immunoblot. The incorporation of 5-bromo-2-deoxyuridine (BrdU) in hippocampal regions was investigated by using immunohistochemical methods. Treatment of Pcer enhanced cognitive performances in the passive avoidance test and Y-maze task. Immunoblotting studies revealed that the phosphorylated CREB and BDNF were significantly increased on hippocampus in the Pcer-treated mice. Immunohistochemical studies showed that the number of immunopositive cells to BrdU was significantly increased in the hippocampal dentate gyrus regions after Pcer-treatment for 7 days. These results suggest that Pcer contribute to enhancing memory and BDNF expression and it could be secondary to the elevation of neurogenesis.

• 생물정신의학
• /
• 제8권1호
• /
• pp.3-19
• /
• 2001

Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.