• 제목/요약/키워드: Dentate gyrus granule cells

검색결과 10건 처리시간 0.017초

Calcium Influx is Responsible for Afterdepolarizations in Rat Hippocampal Dentate Granule Cells

  • Park, Won-Sun;Lee, Suk-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • 제6권3호
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    • pp.143-147
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    • 2002
  • Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of $Na^+$ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic $Na^+$ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about $-49.04{\pm}1.69\;mV\;(n=43,\;mean{\pm}SD)$ and lasting $3{\sim}7$ ms. Increase of extracellular $Ca^{2+}$ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A $K^+$ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM $Ca^{2+}$ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external $Ca^{2+},$ even in the presence of 4-AP (2 mM). A $Na^+$ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular $Ca^{2+}$ influx contributes to the generation of ADP in granule cells.

Developmental changes in GABAA tonic inhibition are compromised by multiple mechanisms in preadolescent dentate gyrus granule cells

  • Pandit, Sudip;Lee, Gyu Seung;Park, Jin Bong
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권6호
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    • pp.695-702
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    • 2017
  • The sustained tonic currents ($I_{tonic}$) generated by ${\gamma}$-aminobutyric acid A receptors ($GABA_{A}Rs$) are implicated in diverse age-dependent brain functions. While various mechanisms regulating $I_{tonic}$ in the hippocampus are known, their combined role in $I_{tonic}$ regulation is not well understood in different age groups. In this study, we demonstrated that a developmental increase in GABA transporter (GAT) expression, combined with gradual decrease in $GABA_AR{\alpha}_5$ subunit, resulted in various $I_{tonic}$ in the dentate gyrus granule cells (DGGCs) of preadolescent rats. Both GAT-1 and GAT-3 expression gradually increased at infantile ($P_{6-8}$ and $P_{13-15}$) and juvenile ($P_{20-22}$ and $P_{27-29}$) stages, with stabilization observed thereafter in adolescents ($P_{34-36}$) and young adults ($P_{41-43}$). $I_{tonic}$ facilitation of a selective GAT-1 blocker (NO-711) was significantly less at $P_{6-8}$ than after $P_{13-15}$. The facilitation of $I_{tonic}$ by SNAP-5114, a GAT-3 inhibitor, was negligible in the absence of exogenous GABA at all tested ages. In contrast, $I_{tonic}$ in the presence of a nonselective GAT blocker (nipecotic acid, NPA) gradually decreased with age during the preadolescent period, which was mimicked by $I_{tonic}$ changes in the presence of exogenous GABA. $I_{tonic}$ sensitivity to L-655,708, a $GABA_AR{\alpha}_5$ subunit inverse agonist, gradually decreased during the preadolescent period in the presence of NPA or exogenous GABA. Finally, Western blot analysis showed that the expression of the $GABA_AR{\alpha}_5$ subunit in the dentate gyrus gradually decreased with age. Collectively, our results suggested that the $I_{tonic}$ regulation of altered GATs is under the final tune of $GABA_AR{\alpha}_5$ subunit activation in DGGCs at different ages.

Physical disector를 이용한 신경세포 및 신경연접 수의 측정 (Estimation of Number of Synapses on a Neuron in the Brain Using Physical Bisector Method)

  • 이계주;유임주
    • Applied Microscopy
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    • 제36권2호
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    • pp.83-91
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    • 2006
  • 신경연접은 다양한 생리적 또는 병적 상태에 반응하여 구조 및 수적 변화를 보이며, 신경연접의 밀도 변화는 신경세포의 활성 조절에 중요한 역할을 하는 것으로 알려져 있다. 따라서 특정 생리적 또는 병적 상태에서 신경연접의 밀도 변화를 명확히 이해하기 위해서는 정확한 정량방법을 이용한 밀도 측정이 필수적이다. 본 연구에서는 physical disector법을 이용하여 흰쥐 뇌의 치아이랑에 위치하는 과립신경세포의 신경연접 수를 측정하였으며, 이를 통해 physical disector의 방법적 정확성을 확인하고자 하였다. 성체 흰쥐를 관류고정한 후 치아이랑의 연속 절편을 얻어 통상적인 전자현미경 시료제작법을 통해 Epon 혼합용액에 포매하였다. Physical disector법을 이용한 밀도 분석 시 연속절편의 정렬, 비교 및 disector frame이 필요하므로 Reconstruct 프로그램을 사용하였다. 동물 당 40장의 $1{\mu}m$ 연속절편을 제작하여 과립신경세포체의 밀도를 측정하였으며, 15장의 80nm연속절편으로부터 bidirectional disector법을 이용하여 과립신경세포와 내측 관통로(medial perforant path) 간 신경 연접의 밀도를 분석하였다. 과립신경세포의 세포체와 신경연접은 각각 과립층과 분자층에 위치하기 때문에 하나의 신경세포가 가지는 신경연접의 수를 측정하기 위해서는 각 층의 부피를 고려하는 것이 요구된다. 따라서 과립층에 대한 분자층의 부피비율을 측정하였다. 실험결과, 흰쥐 치아이랑에 위치하는 하나의 과립세포당 약 6,500개의 신경연접의 존재한다는 사실을 확인하였으며, 이는 다른 연구자들의 결과와 유사하였다. 본 연구로부터 physical disector법은 특정 생리적 또는 병적 조건에서 나타나는 신경세포 및 신경연접의 수적 변화를 정확히 측정할 수 있는 유용한 정량방법임을 알 수 있었다. 향후 physical disector법을 이용하여 다양한 실험동물모델의 신경연접 변화를 분석하는 것은 신경연접의 형태적 가소성을 이해하는데 이바지할 것으로 생각된다.

TWIK-1/TASK-3 heterodimeric channels contribute to the neurotensin-mediated excitation of hippocampal dentate gyrus granule cells

  • Choi, Jae Hyouk;Yarishkin, Oleg;Kim, Eunju;Bae, Yeonju;Kim, Ajung;Kim, Seung-Chan;Ryoo, Kanghyun;Cho, Chang-Hoon;Hwang, Eun Mi;Park, Jae-Yong
    • Experimental and Molecular Medicine
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    • 제50권11호
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    • pp.4.1-4.13
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    • 2018
  • Two-pore domain $K^+$ (K2P) channels have been shown to modulate neuronal excitability. The physiological role of TWIK-1, the first identified K2P channel, in neuronal cells is largely unknown, and we reported previously that TWIK-1 contributes to the intrinsic excitability of dentate gyrus granule cells (DGGCs) in mice. In the present study, we investigated the coexpression of TWIK-1 and TASK-3, another K2P member, in DGGCs. Immunohistochemical staining data showed that TASK-3 proteins were highly localized in the proximal dendrites and soma of DGGCs, and this localization is similar to the expression pattern of TWIK-1. TWIK-1 was shown to associate with TASK-3 in DGGCs of mouse hippocampus and when both genes were overexpressed in COS-7 cells. shRNA-mediated gene silencing demonstrated that TWIK-1/TASK-3 heterodimeric channels displayed outwardly rectifying currents and contributed to the intrinsic excitability of DGGCs. Neurotensin-neurotensin receptor 1 (NT-NTSR1) signaling triggered the depolarization of DGGCs by inhibiting TWIK-1/TASK-3 heterodimeric channels, causing facilitated excitation of DGGCs. Taken together, our study clearly showed that TWIK-1/TASK-3 heterodimeric channels contribute to the intrinsic excitability of DGGCs and that their activities are regulated by NT-NTSR1 signaling.

Different expression of human GFAP promoter-derived GFP in different subsets of astrocytes in the mouse brain

  • Moon, Young-Hye;Kim, Hyun-Jung;Kim, Joo-Yeon;Kim, Hyun;Kim, Woon-Ryoung;Sun, Woong
    • Animal cells and systems
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    • 제15권4호
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    • pp.268-273
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    • 2011
  • Transgenic mice expressing green fluorescent protein (GFP) under the control of human glial fibrillary acidic protein promoter (hGFAP) have been utilized for in vivo labeling of astrocytes. Although it has been considered that virtually all astrocytes express GFP in this transgenic mouse, we found that different subsets of GFAP-expressing astrocytes express considerably different levels of GFP in the adult brain. Astrocytes in the spinal cord, the molecular layer of thecerebellum, meninges, white matter, corpus callosum and blood vessels exhibited strong GFP, whereas subsets of astrocytes associated with granule cells in the cerebellum and dentate gyrus did not or only marginally exhibited GFP. We also found that a small subset of GFP-expressing cells in the periglomeruli of the olfactory bulb did not express GFAP immunoreactivity. Collectively, these results suggest that human GFAP promoter-derived GFP expression does not faithfully recapitulate the endogenous GFAP expression in mice, suggesting that upstream regulatory mechanisms controlling GFAP transcription are different in different populations of astrocytes, and may reflect the functional diversity of astrocytes.

Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-κB signaling pathway in mice

  • Seong, Kyung-Joo;Lee, Hyun-Gwan;Kook, Min Suk;Ko, Hyun-Mi;Jung, Ji-Yeon;Kim, Won-Jae
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권1호
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    • pp.41-51
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    • 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.

우울증의 새로운 신경생물학 (The New Neurobiology of Depression)

  • 김용구
    • 생물정신의학
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    • 제8권1호
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    • pp.3-19
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    • 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.

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Asymmetrical Volume Loss in Hippocampal Subfield During the Early Stages of Alzheimer Disease: A Cross Sectional Study

  • Kannappan, Balaji
    • 통합자연과학논문집
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    • 제11권3호
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    • pp.139-147
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    • 2018
  • Hippocampal atrophy is a well-established imaging biomarker of Alzheimer disease (AD). However, hippocampus is a non-homogenous structure with cytoarchitecturally and functionally distinct sub-regions or subfield, with each region performing distinct functions. Certain regions of the subfield have shown selective vulnerability to AD. Here, we are interested in studying the effects of normal aging and mild cognitive impairment on these sub-regional volumes. With a reliable automated segmentation technique, we segmented these subregions of the hippocampus in 101 cognitively normal (CN), 135 early mild cognitive impairment (EMCI), 67 late mild cognitive impairment (LMCI) and 48 AD subjects. Thereby, dividing the hippocampus into hippocampal tail (tail), subiculum (SUB), cornu ammonis 1 (CA1), hippocampal fissure (fissure), presubiculum (PSUB), parasubiculum (ParaSUB), molecular layer (ML), granule cells/molecular layer/dentate gyrus (GCMLDG), cornu ammonis 3(CA3), cornu ammonis 4(CA4), fimbria and hippocampal-amygdala transition area (HATA). In this cross sectional study of 351 ADNI subjects, no differences in terms of age, gender, and years of education were observed among the groups. Though, the groups had statistically significant differences (p < 0.05 after the multiple comparison correction) in the Mini-Mental State Examination (MMSE) scores. There was asymmetrical volume loss in the early stages of AD with the left hemisphere showing volume loss in regions that were unaffected in the right hemisphere. Bilateral parasubiculum, right cornu ammonis 1, 3 and 4, right fimbria and right HATA regions did not show any volume loss till the late MCI stages. Our findings suggest that the hippocampal subfield regions are selectively vulnerable to AD and also that these vulnerabilities are asymmetrical especially during the early stages of AD.

반복 스트레스에 의한 흰쥐 해마조직내 신경전구세포의 생성과 brain-derived neurotrophic factor (BDNF) mRNA 발현 변동에 미치는 고려홍삼 사포닌의 반복 투여 효과 (Effects of Korea Red Ginseng Total Saponin on Repeated Unpredictable Stress-induced Changes of Proliferation of Neural Progenitor Cells and BDNF mRNA Expression in Adult Rat Hippocampus)

  • 김동훈;곽규환;이금주;김성진;신유찬;전보권;신경호
    • Journal of Ginseng Research
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    • 제28권2호
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    • pp.94-103
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    • 2004
  • 본 연구 결과를 통하여 홍삼 성분인 고려홍삼 사포닌을 반복 투여시 흰쥐 해마 SGZ 부위의 신경전구세포 생성이 유의하게 증가되었으며, 이와 같은 경향은 반복 스트레스에 노출되어도 유지되었다. 또한 스트레스를 가하지 않은 흰쥐에서 고려홍삼 사포닌 반복 투여시 해마 CA3와 CA1 부위에서 BDNF mRNA의 발현이 증가되었으나, 반복 스트레스를 가한 흰쥐의 CA3와 CA1부위에서 BDNF mRNA의 감소를 차단하지는 못하였다. 따라서 고려홍삼 사포닌 반복 처치에 의한 해마 신경전구세포의 생성에 BDNF 보다는 다른 요인이 관여할 가능성이 클 것으로 추정된다.

Stem cell-secreted 14,15-epoxyeicosatrienoic acid rescues cholesterol homeostasis and autophagic flux in Niemann-Pick-type C disease

  • Kang, Insung;Lee, Byung-Chul;Lee, Jin Young;Kim, Jae-Jun;Sung, Eun-Ah;Lee, Seung Eun;Shin, Nari;Choi, Soon Won;Seo, Yoojin;Kim, Hyung-Sik;Kang, Kyung-Sun
    • Experimental and Molecular Medicine
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    • 제50권11호
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    • pp.8.1-8.14
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    • 2018
  • We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Our screening of the CYP2J family indicated a dysregulation in the CYP system in a cerebellar-specific manner. Moreover, in Purkinje cells, CYP2J6 showed an elevated expression level compared to that of astrocytes, granule cells, and microglia. In this regard, we found that one CYP metabolite, 14,15-EET, acts as a key mediator in ameliorating cholesterol accumulation. In confirming this hypothesis, 14,15-EET treatment reduced the accumulation of cholesterol in human NPC1 patient-derived fibroblasts in vitro by suppressing cholesterol synthesis and ameliorating the impaired autophagic flux. We show that the reduced activity within the CYP system in the cerebellum could cause the neurological symptoms of NPC1 patients, as 14,15-EET treatment significantly rescued cholesterol accumulation and impaired autophagy. We also provide evidence that the intranasal administration of hUCB-MSCs is a highly promising alternative to traumatic surgical transplantation for NPC1 patients.