Glucose sensitivity and its physiological role of midbrain nucleus substantia nigra pars reticulata

中脑黑质网状核的葡萄糖敏感性及其生理作用

基本信息

  • 批准号:
    17590182
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

GABArgic neurons in the substantia nigra pars reticulata (SNr) exhibit spontaneous firing activity among highest in the brain. Continuous supply of oxygen and glucose is essential to ensure such neuronal activity. Indeed, we have shown that the SNr neurons exert a crtical role in sensing hypoxic conditions and suppressing hypoxia-induced propagation of generalized seizure via opening of ATP-sensitive potassium channels (K_<ATP>). Moreover, SNr neurons exhibited, in acute slice preparations, glucose-sensitivity, an increase of firing when extracellular glucose concentration is lowered, through K_<ATP> channel-independent mechanisms. However, it was unclear if the glucose sensitivity is an intrinsic property of the SNr neurons or is produced by cell-to-cell interactions such as synaptic transmissions. In the present study, we aimed to clarify this using acutely dissociated SNr neurons with perforated patch clamp techniques (Yamada K et al., the 84th Annual Meeting of the Physiological So … More ciety of Japan). 1.Most acutely dissociated SNr GABAergic neurons (10/14;〜70%) showed significant depolarization (5.7±2.4 mV for 4 mM glucose;31C) when extracellular glucose concentration was lowered from 10 mM to 4-8 mM in a concentration-dependent manner, suggesting that the resting potentials of SNr neurons can be regulated by extracellular glucose concentration. 2.Similarly to in the slice, acutely disscoiated SNr neurons responded to lowering glucose by either an increase, an increase followed by a decrease, no change, and a decrease, indicating that intrinsic property of SNr neurons contributes to the glucose sensitivity. 3.Upon lowering glucose, although a portion of acutely dissociated SNr neurons showed repeated abrupt increases in firing rate as in the slice, an individual increase did not persist long (such as for minutes ; termed as multiminute oscillation) compared to the slice preparation. Rather, the firing pattern consisted of discreate sets of short duration (0.5-1 sec) bursts of high frequency firing, wherease SNr neurons in the slice showed tonic firing of over 100 Hz for 10-20 sec with no burst when SNr neurons were extracellularly recorded, suggesting that cell-to-cell interaction and/or intact morphology may be important for the low glucose-induced stable increase of firing. The multiminute oscillation in the slice was inhibited by Low Ca (high Mg), suggesting that synaptic transmissions are required for the persistent increase in the high-frequency firing. The oscillation was not affected by blockade of GABA_A, GABA_B, non-NMDA, and NMDA receptors. We are currently investigating candidate transmitters. 4.To elucidate the physiological role of the glucose sensitivity of SNr neurons, we are developing glucose-sensing electrodes by a new approach. Optical imaging using a fluorescent glucose derivative 2-NBDG (Yamada K et al., Nature protocol,2007) is also appliled to understand the role of cell-to-cell interaction in the glucose sensitivity in the SNr. Less
黑质网状部(SNr)中的GABA能神经元在脑中表现出最高的自发放电活动。氧气和葡萄糖的持续供应对确保这种神经元活动至关重要。事实上,我们已经证明,SNr神经元在感受缺氧条件和通过开放ATP敏感性钾通道(K_2)抑制缺氧诱导的全身性癫痫发作的传播中发挥关键作用<ATP>。此外,SNr神经元在急性脑片制备中表现出葡萄糖敏感性,当细胞外葡萄糖浓度降低时,通过K_<ATP>通道非依赖性机制增加放电。然而,目前尚不清楚葡萄糖敏感性是SNr神经元的固有特性还是由细胞间相互作用(如突触传递)产生的。在本研究中,我们的目的是使用穿孔膜片钳技术使用急性分离的SNr神经元来阐明这一点(Yamada K等人,第84届美国生理学会年会 ...更多信息 日本)。1.当细胞外葡萄糖浓度从10 mM降低到4-8 mM时,大多数急性分离的SNr GABA能神经元(10/14;约70%)显示出显著的去极化(对于4 mM葡萄糖为5.7±2.4 mV; 31 C),这表明SNr神经元的静息电位可受细胞外葡萄糖浓度的调节。2.与切片中相似,急性损伤的SNr神经元对降低葡萄糖的反应为增加、增加后减少、无变化和减少,表明SNr神经元的内在特性有助于葡萄糖敏感性。3.在降低葡萄糖时,虽然一部分急性分离的SNr神经元表现出重复的突然增加的放电率在切片中,一个单独的增加并没有持续很长时间(如分钟;称为多分钟振荡)相比,切片制备。相反,放电模式由高频放电的短持续时间(0.5-1秒)爆发的离散集合组成,其中当细胞外记录SNr神经元时,切片中的SNr神经元显示超过100 Hz的强直放电持续10-20秒而没有爆发,这表明细胞间相互作用和/或完整的形态对于低葡萄糖诱导的放电稳定增加可能是重要的。切片中的多分钟振荡被低钙(高镁)抑制,表明突触传递是高频放电持续增加所必需的。阻断GABA_A、GABA_B、非NMDA受体和NMDA受体均不影响这种振荡。我们目前正在调查候选发射机。4.为了阐明SNr神经元葡萄糖敏感性的生理作用,我们正在通过一种新的方法研制葡萄糖敏感电极。使用荧光葡萄糖衍生物2-NBDG的光学成像(Yamada K等人,Nature protocol,2007)也被应用于理解细胞间相互作用在SNr中葡萄糖敏感性中的作用。少

项目成果

期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Disruption of Kir6.2-containing ATP-sensitive potassium channels impairs maintenance of hypoxic gasping in mice
含有 Kir6.2 的 ATP 敏感钾通道的破坏会损害小鼠缺氧喘气的维持
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Miyake;A.;Yamada;K.;Kosaka;T.,Miki;T.;Seino;S.;Inagaki;N.
  • 通讯作者:
    N.
System for simultaneously monitoring heart and breathing rate in mice using a piezoelectric transducer
Expression of ABCA2 protein in both non-myelin-forming and myelin-forming Schwann cells in the rodent peripheral nerve
ABCA2蛋白在啮齿动物周围神经非髓磷脂形成和髓磷脂形成雪旺细胞中的表达
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Saito;T.;Yamada;K.;Wang;Y.;Tanaka;Y.;Ohtomo;K.;Ishikawa;K.;and Inagaki;N.
  • 通讯作者:
    N.
Expression of ABCA2 protein in human vestibular schwannoma and peripheral nerve.
ABCA2蛋白在人前庭神经鞘瘤和周围神经中的表达。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wang;Y.;et al.
  • 通讯作者:
    et al.
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YAMADA Katsuya其他文献

YAMADA Katsuya的其他文献

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{{ truncateString('YAMADA Katsuya', 18)}}的其他基金

Structure-function analyses of inhibitory terminals in midbrain nucleus substantia nigra
中脑黑质核抑制末端的结构功能分析
  • 批准号:
    23650203
  • 财政年份:
    2011
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Molecular mechanisms and roles of cortical thin vessels on regulation of activity-dependent cerebral blood flow changes
皮质细血管调节活动依赖性脑血流变化的分子机制和作用
  • 批准号:
    19590203
  • 财政年份:
    2007
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Real-time analysis on activity-dependent glucose uptake by usiug brain slices
使用脑切片实时分析活动依赖性葡萄糖摄取
  • 批准号:
    13680893
  • 财政年份:
    2001
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Neurite outgrowth in mature cerebral cortex investigated by a slice culture method.
通过切片培养方法研究成熟大脑皮层中的神经突生长。
  • 批准号:
    07808090
  • 财政年份:
    1995
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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蚊子吸血和交配生理的肽调节
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RAPID:COVID-19 导致生态旅游和补充喂养停止:对野生动物生理学、繁殖和微生物组的影响
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蚊子的水合状态是一种改变摄食前宿主相互作用和摄食后生理机能的机制
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蚊子的水合状态是一种改变摄食前宿主相互作用和摄食后生理机能的机制
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蚊子吸血和交配生理的肽调节
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Elucidating the physiology of nesfatin-1-expressing neurons in feeding suppression in rats
阐明表达 nesfatin-1 的神经元在大鼠摄食抑制中的生理学
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