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1、 膠質(zhì)細(xì)膠質(zhì)細(xì)胞胞兩類神經(jīng)細(xì)胞：神經(jīng)元（信號傳遞和處理）膠質(zhì)細(xì)胞（支持營養(yǎng)）星形膠質(zhì)細(xì)胞（Astrocytes）少突膠質(zhì)細(xì)（Oligodendrites）小膠質(zhì)細(xì)胞（Microglia）雪旺氏細(xì)胞（Schwann cell）Camillo Golgi(18431926）神經(jīng)網(wǎng)絡(luò)的概念和神經(jīng)元學(xué)說神經(jīng)網(wǎng)絡(luò)的概念和神經(jīng)元學(xué)說Signal transmission between neurons:electrical-chemical-electrical 2Pre-synaptic neuronPost-synaptic neuron Rudolph Virchow(18211902)德國病理學(xué)家

2、在觀察了大量的人腦標(biāo)本的基礎(chǔ)上，在1858年出版的Cellular Pathology中系統(tǒng)地闡述了神經(jīng)膠質(zhì)（Neural glia）的概念 神經(jīng)膠質(zhì)（Neural glia）概念的提出 Camillo Golgi（18431926）營養(yǎng)假說 Robert Remak(1815-1865)首次認(rèn)識到那些較粗的周圍神經(jīng)纖維有鞘樣物質(zhì)包繞，并有胞核存在，而細(xì)的纖維沒有類似的結(jié)構(gòu)。Schwann 詳細(xì)描述了這些結(jié)構(gòu)。雖然他們都觀察到了鞘樣結(jié)構(gòu)附近有胞核存在，但都沒有意識到它們可能是與形成鞘樣結(jié)構(gòu)有關(guān)的細(xì)胞。Ranvier 在1871年首次將這些細(xì)胞稱為雪旺細(xì)胞（Schwann cell）。認(rèn)為這些分

3、開的節(jié)狀分布并不是組織固定形成的假象，并認(rèn)識到這些節(jié)狀結(jié)構(gòu)是各自獨立的，每一節(jié)都有它自己相聯(lián)系的雪旺細(xì)胞。后人把節(jié)與節(jié)連接的部位稱為郎飛氏結(jié)（node of Ranvier）。但直到電鏡技術(shù)的應(yīng)用，才完全接受雪旺細(xì)胞產(chǎn)生髓鞘的學(xué)說。Theodor Schwann(1810-1882)Louis-Antoine Ranvier(1835-1922)Cajal的學(xué)生,發(fā)現(xiàn)少突膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞。認(rèn)為少突膠質(zhì)細(xì)胞和星形膠質(zhì)細(xì)胞同屬于腦內(nèi)的大膠質(zhì)細(xì)胞。推測少突膠質(zhì)細(xì)胞具有組成并維持中樞神經(jīng)髓鞘的功能。然而只到電鏡技術(shù)問世，中樞髓鞘是由少突膠質(zhì)細(xì)胞生成的觀點才得到公認(rèn)。由于Cajal沒能重復(fù)出Rio-

4、Hortega的結(jié)果，不相信少突膠質(zhì)細(xì)胞的存在，并導(dǎo)致了他們合作關(guān)系的破裂。認(rèn)為小膠質(zhì)細(xì)胞來源于中胚層，并具有遷移和吞噬的特性。提出小膠質(zhì)細(xì)胞是不同于神經(jīng)元（第一類）和大膠質(zhì)細(xì)胞（第二類）的中樞第三類細(xì)胞。首次描述了小膠質(zhì)細(xì)胞具有類阿米巴樣和分枝狀的兩種狀態(tài)，認(rèn)為在病理情況下，小膠質(zhì)細(xì)胞可以從非活性的分枝狀轉(zhuǎn)變成具有吞噬性的類阿米巴狀的活性狀態(tài)，具有巨噬細(xì)胞那樣的運動和吞噬的功能。Pio del Rio-Hortega（1882-1945）1910年描述了膠質(zhì)細(xì)胞在各種腦疾病狀態(tài)下的膠質(zhì)細(xì)胞的反應(yīng)變化。認(rèn)為這些發(fā)生了阿米巴樣變化的膠質(zhì)細(xì)胞失去了正常時具有的對神經(jīng)元的支持作用，可能對變性壞死的神

5、經(jīng)起到消化清除作用。在他第一次報道的老年癡呆病例中，描述了病灶周圍的處于激活狀態(tài)的膠質(zhì)細(xì)胞。Rio-Hortega對這些活化的膠質(zhì)細(xì)胞特性進(jìn)行了更細(xì)致的描述，并把活化的星形膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞區(qū)別開來。Alois Alzheimer(1864-1915)Glial cell:perfect K+electrodeStephen William Kuffler(1913 1980)lMembrane potential:-90 mMlCoupled by gap junction Whole-Cell Recording in Hippocampal SliceGlu TransporterGl

6、uAstrocyteAstrocyteClearance of extracellular neurotransmitters 1 H+3 Na+1 Glu-1 K+3 Na+2 K+ATPADP_ _+_ _ _ _K+Na+1.Electrogenic2.Driven by Na,K gradient and negative membrane potential3.Modifiable4.Reversible under certain condition5.Channel function Na+-K+pumpGlu transporterMetabolite couplingglut

7、aminglutamateSignal transmission between neurons:electrical-chemical-electrical 2Pre-synaptic neuronPost-synaptic neuronGlial cells express various channels and receptorsRansom,Ketternmann,Barres,et al.Charles et al.,Neuron.1991 Jun;6(6):983-92.Nedergaard,M(1994).Science 263,1768-1771.Parpura,and Ha

8、ydon,PG(1994).Nature 369,744-747.Neuron-glia crosstalk:mediated by Ca 2+wavesNeuron-glia interaction:New roles of glial cellsGap junctionMechanisms of intercellular Ca 2+wave propagationNeuron-glia signaling and the dynamic control of brain microcirculationCells in the brain:NeuronsGliaGlia-neuron r

9、atio in the brain:Drosophila:25%Rat:65%Human:90%中樞髓鞘少突膠質(zhì)細(xì)胞P8P14P20P50NG2 glial cells:oligodendritic precursor cells(OPC)Distinctive electrophysiological propertiesNeuronNG2Astrocytes髓鞘相關(guān)抑制分子等神經(jīng)再生 抑制分子的表達(dá)和分泌膠質(zhì)疤痕對神經(jīng)生長的物理 屏障和血供障礙過度炎癥反應(yīng)新生軸突的再髓鞘化障礙中樞神經(jīng)修復(fù)再生障礙的決定因素?fù)p傷后微環(huán)境：小膠質(zhì)細(xì)胞Perry and OConnor,ASN Neuro.20

10、10 Oct 14;2(5):e00047ATP induced microglial chemotaxis.Functions of P2Y receptors in microgliaUDP:Eat me signal P2Y6-Phagocytosis ATP:Signal for coming and drinkingP2Y12 -Chemotaxis P2Y4 -Macropinocytosis(PI3K)CNSl星形膠質(zhì)細(xì)胞星形膠質(zhì)細(xì)胞（Astrocytes）代謝，營養(yǎng)，信號（Ca2+波）l少突膠質(zhì)細(xì)胞少突膠質(zhì)細(xì)胞（Oligodendrites）中樞髓鞘 l小膠質(zhì)細(xì)胞小膠質(zhì)細(xì)胞（M

11、icroglia）吞噬、免疫 PNS 雪旺氏細(xì)胞雪旺氏細(xì)胞（Schwann cell）周圍髓鞘 Glial cell:perfect K+electrodeGlu TransporterGluAstrocyteAstrocyteClearance of extracellular neurotransmitters 1 H+3 Na+1 Glu-1 K+3 Na+2 K+ATPADP_ _+_ _ _ _K+Na+1.Electrogenic2.Driven by Na,K gradient and negative membrane potential3.Modifiable4.Reversible under certain condition5.Channel function Na+-K+pumpGlu transporterMetabolite couplingglutaminglutamateCharles et al.,Neuron.1991 Jun;6(6):983-92.Nedergaard,M(1994).Science 263,1768-1771.Parpura,and Haydon,PG(1994).Nature 369,744-747.Neuron-glia crosstalk:mediated by Ca 2+waves