Endocannabinoids in synaptic plasticity and neuroprotection.
Endocannabinoids in synaptic plasticity and neuroprotection.
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DOI：
10.1177/1073858414524632
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Xu JY;Chen C
内源性大麻素（Endocannabinoids，eCB）是参与多种生理、药理和病理过程的内源性脂质介质。虽然eCB系统的激活主要通过作用于脑中突触前表达的CB 1受体来诱导对GABA能和海马能突触传递和可塑性的抑制作用，但积累的信息表明eCB信号传导也能够促进或增强海马中的兴奋性突触传递。最近的研究表明，时空启动输入可诱导Schaffer侧支（SC）-CA 1突触兴奋性突触传递的持久增强，同时伴有海马CA 1锥体神经元抑制性突触传递（I-LTD）的长期抑制。SC-CA 1突触处的这种输入定时依赖性持久突触增强由2-花生四烯酸甘油（2-AG）信号传导介导，所述信号传导由突触后NMDA受体、I组代谢型谷氨酸受体（mGluRs）的激活和细胞内Ca 2+的同时升高触发。新出现的证据也表明，2-AG是一种重要的信号介质，通过CB 1/2受体依赖性和/或非依赖性机制发挥其抗炎和神经保护作用，以响应有害的损伤，从而保持脑内稳态。核受体蛋白过氧化物酶体增殖物激活受体-γ（peroxisome proliferator-activated receptor-γ，PPARγ）的激活是2-AG信号介导的神经炎症反应和保护神经元的重要机制之一。因此，在这篇综述中总结的信息表明，eCB信号在维持大脑功能完整性方面的作用比我们以前认为的要大。
Endocannabinoids (eCBs) are endogenous lipid mediators involved in a variety of physiological, pharmacological, and pathological processes. While activation of the eCB system primarily induces inhibitory effects on both GABAergic and glutamatergic synaptic transmission and plasticity through acting on presynaptically-expressed CB1 receptors in the brain, accumulated information suggests that eCB signaling is also capable of facilitating or potentiating excitatory synaptic transmission in the hippocampus. Recent studies show that a long-lasting potentiation of excitatory synaptic transmission at Schaffer collateral (SC)-CA1 synapses is induced by spatiotemporally primed inputs, accompanying with a long-term depression of inhibitory synaptic transmission (I-LTD) in hippocampal CA1 pyramidal neurons. This input-timing-dependent long-lasting synaptic potentiation at SC-CA1 synapses is mediated by 2-arachidonoylglycerol (2-AG) signaling triggered by activation of postsynaptic NMDA receptors, group I metabotropic glutamate receptors (mGluRs), and a concurrent rise in intracellular Ca2+. Emerging evidence now also indicates that 2-AG is an important signaling mediator keeping brain homeostasis by exerting its anti-inflammatory and neuroprotective effects in response to harmful insults through CB1/2 receptor-dependent and/or independent mechanisms. Activation of the nuclear receptor protein peroxisome proliferator-activated receptor-γ (PPARγ) apparently is one of the important mechanisms in resolving neuroinflammation and protecting neurons produced by 2-AG signaling. Thus, the information summarized in this review suggests that the role of eCB signaling in maintaining integrity of brain function is greater than what we thought previously.
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DOI：
10.1007/978-3-540-88955-7_6
发表时间：
2009-01-01
期刊：
BEHAVIORAL NEUROBIOLOGY OF THE ENDOCANNABINOID SYSTEM
影响因子：
--
作者：
Alger, Bradley E.
通讯作者：
Alger, Bradley E.
影响因子：
15.9
作者：
ALGER, BE;PITLER, TA
通讯作者：
PITLER, TA
影响因子：
25
作者：
Carlson, G;Wang, Y;Alger, BE
通讯作者：
Alger, BE
影响因子：
5.3
作者：
Bender, VA;Bender, KJ;Feldman, DE
通讯作者：
Feldman, DE
影响因子：
2.9
作者：
Bright, John J.;Kanakasabai, Saravanan;Chearwae, Wanida;Chakraborty, Sharmistha
通讯作者：
Chakraborty, Sharmistha