Crosstalk Ntawm Neuron Thiab Glial Cells hauv Oxidative Injury Thiab Neuroprotection Part 2
Mar 22, 2024
3. Astrocytes
3.1. Astrocytes hauv hlwb
Astrocytes yog qhov muaj zog tshaj plaws thiab muaj ntau ntawm tib neeg lub hlwb hlwb lub luag haujlwm los tswj lub hlwb homeostasis. Astrocytes yog hu ua cov hlwb hauv thaj av thiab muaj ntau txoj haujlwm txuas ntxiv nrog cov hlwb uas nyob ib sab; Yog li, lawv formorganized anatomical domains nrog txuam functional syncytia [26].
Astrocytes yog hom cell tseem ceeb hauv lub hlwb. Cov hlwb no yog lub luag haujlwm rau kev tiv thaiv thiab txhawb nqa neurons thiab tswj kev ua haujlwm ntawm tag nrho cov paj hlwb. Nyob rau hauv xyoo tas los no, ntau thiab ntau cov kev tshawb fawb tau pom tias astrocytes tseem muaj feem cuam tshuam nrog kev tsim thiab kev saib xyuas ntawm tib neeg kev nco.
Kev tshawb fawb tau pom tias astrocytes tuaj yeem cuam tshuam kev sib txuas ntawm cov neurons, yog li cuam tshuam rau kev tsim thiab khaws cia ntawm kev nco. Cov hlwb glial no tuaj yeem tshem tawm cov khib nyiab thiab lwm yam khoom tsis zoo los ntawm cov neurons. Thaum tswj kev noj qab haus huv ntawm lub paj hlwb, lawv kuj pab txhim kho peb lub cim xeeb.
Tsis tas li ntawd, cov kws tshawb fawb tau tshawb pom tias astrocytes tsim cov molecule hu ua FGF2, uas ua lub luag haujlwm tseem ceeb hauv kev txhim kho kev kawm thiab kev nco. Cov kev sim tau pom tias nce cov ntsiab lus ntawm FGF2 hauv astrocytes tuaj yeem txhim kho kev kawm muaj peev xwm thiab kev nco ntawm nas.
Txawm tias zoo siab dua, qee qhov kev tshawb fawb tau pom tias kev tswj hwm txoj kev noj qab haus huv tuaj yeem txhawb kev loj hlob ntawm astrocyte thiab ua haujlwm. Piv txwv li, kev tawm dag zog tsis tu ncua, noj zaub mov zoo, thiab pw tsaug zog txaus tuaj yeem txhawb kev loj hlob thiab kev ua haujlwm ntawm astrocytes, uas tuaj yeem pab txhim kho peb lub cim xeeb.
Yog li ntawd, txawm hais tias qee yam tsis zoo hauv lub neej, xws li haus ntau dhau lossis siv qee yam tshuaj, yuav cuam tshuam rau kev loj hlob thiab kev ua haujlwm ntawm astrocytes, tseem muaj ntau yam kev ntsuas uas peb tuaj yeem ua los txhim kho lawv txoj haujlwm. Tsuav peb muaj tus cwj pwm zoo thiab ua neej nyob kom noj qab nyob zoo, peb tuaj yeem muaj peev xwm nco tau zoo dua thiab muaj kev noj qab haus huv zoo dua. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola muaj antioxidant, tiv thaiv kev mob, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidation thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv cov kab mob. kev noj qab haus huv ntawm lub paj hlwb. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhawb kev loj hlob thiab kho cov paj hlwb, yog li txhim kho kev sib txuas thiab kev ua haujlwm ntawm neural networks. Cov teebmeem no tuaj yeem pab txhim kho kev nco, kev kawm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv kev loj hlob ntawm kev paub tsis meej thiab kab mob neurodegenerative.
Nyem Paub txhawm rau txhim kho lub cim xeeb luv luv
Astrocytes projectvascular txheej txheem (astrocytic kawg-taw) mus rau hauv cov hlab ntsha intraparenchymal thiab ensheaththe hlab ntsha los tswj kev txav ntawm cov molecules thiab cov hlwb ntawm cov vascularcompartment thiab lub hlwb [27].
Tib neeg astrocytes feem ntau muab faib ua plaub pawg raws li lawv cov neuroanatomy [28]. Ua ntej, interlaminar astrocytes muaj ib puag ncig cellbody thiab cov txheej txheem luv luv thiab nyob hauv txheej I ntawm lub cortex. Qhov thib ob, protoplasmicastrocytes muaj nyob rau hauv cov teeb meem grey thiab nyob rau hauv txheej II-VI ntawm lub cortex. Lawv yog cov feem ntau astrocytes thiab muaj ntau txheej txheem thiab ib tug bushy morphology.
Qhov thib peb, varicose projection astrocytes nyob rau hauv txheej V-VI thiab muaj cov txheej txheem luv luv nrog los ntawm ib mus rau tsib txheej txheem ntev dua uas yuav ua haujlwm hauv kev sib txuas lus ntev hauv lub cortex. Plaub, fibrous astrocytes nyob hauv cov teeb meem dawb thiab yog cov cell loj dua uas muaj cov txheej txheem tsawg dua. Cov txheej txheem Fibrous astrocyte xa ntau qhov txuas mus rau oligodendroglia uas qhwv myelinated axons [29].
Astrocytes kuj tau muab faib ua hom I-III raws li lawv cov yam ntxwv morphological, xws li lub cev loj ntawm lub cev, tus lej ntawm cov txheej txheem, thickness ntawm cov txheej txheem, kev taw qhia ntawm cov txheej txheem, thiab qhov ntev ntawm cov txheej txheem.
Hom Iastrocytes yog tus cwj pwm los ntawm lub cev me me thiab ntau cov txheej txheem luv luv. Hom IIastrocytes yog tus cwj pwm los ntawm cov duab bipolar thiab cov txheej txheem ntev. Hom III astrocytes muaj tus cwj pwm los ntawm lub hnub qub zoo thiab cov txheej txheem ntev [30,31].
Kev ua haujlwm ntawm astrocytesis los pab cov neurons los ntawm kev ua si txhawb nqa hauv kev ua haujlwm synaptic thiab kev hloov pauv ntawm neurotransmission. Cov txheej txheem ntawm astrocytes ensheath synapses thiab muaj ntau yam receptors rau neurotransmitters, cytokines, loj hlob yam, thiab ion channels.
Astrocytes raug cuam tshuam los ntawm intracellular Ca2+ tso tawm los ntawm extracellular glutamate, thiab tswj theionic tshuav nyiaj li cas ntawm synapses los ntawm nce intracellular Ca2+ qib tom qab secretion ntawm ntau gliotransmitters, xws li glutamate, purines, GABA, thiab D-serine [ 32,33]Neurons muaj kev nkag siab zoo rau cov kev hloov me me hauv lub hlwb microenvironment, txawm tias kev xav ntawm metabolic noj yog siab.
Lub luag haujlwm ntawm astrocytes nyob rau hauv lub hlwb ib txwm yog kev saib xyuas ntawm extracellular homeostasis los ntawm glutamate uptake thiab recycling, K + buffering, muab lub zog substrates, pH buffering, thiab tiv thaiv oxidative kev nyuaj siab [28].
3.2. Astrocytes hauv Oxidative Injury
Astrocytes muaj nyob rau hauv ib qho chaw so lossis reactive hauv lub hlwb, raws li qhia hauv daim duab 2. Reactive astrocytes tso cov inflammatory cytokines xws li TNF thiab ROS, thiab tsim glialscars uas impede axon regeneration thiab neurite outgrowth [34–36].
Activated astrocytesaid nyob rau hauv kev rov ua haujlwm ntawm lub hlwb tom qab raug mob tab sis tuaj yeem ua rau neurotoxic. Reactive astrocytesrelease nitric oxide (NO) rau hauv qhov chaw extracellular; Qhov no tuaj yeem ua rau muaj kev raug mob neuronal thiab tuag los ntawm kev nce lipid peroxidation, mitochondrial impairment, thiab inducing DNAstrand so [37].
Lub astrocytic antioxidant system sib npaug ROS (superoxides, hydroxylradicals, thiab nitric monoxide) uas ib txwm ua thaum lub sij hawm oxygen metabolism los ntawm CNS [38]. Oxidative stress nyob rau hauv reactive astrocytes ua rau lub sij hawm ntev ntawm cov proteins, xws li connexins, glutamate transporters, thiab enzymes, uas cuam tshuam kev cuam tshuam ntawm astrocytes thiab neurons [39].
Lub glutamate uptake los ntawm astrocytere yuav tsum muaj lub zog siab, xav tau ntau tshaj ib qho ATP molecule rau ib glutamatetake-up. Txawm li cas los xij, qhov tsis muaj ATP cuam tshuam nrog cov txheej txheem ntawm ROS-vim glutamateuptake blockade hauv astrocytes [40,41]. Thaiv astrocyte glutamate transporters nce neurotoxicity los ntawm potentiating neuronal excitability thiab excitatory neurotransmission [42].
Kev ntxhov siab oxidative tsim los ntawm astrocytes feem ntau tshwm sim los ntawm mitochondria-derivedoxidative stress, NADPH-derived oxidative stress, thiab RNS ntau lawm. Mitochondriaare faib rau hauv lub cev ntawm tes thiab cov txheej txheem nyias thiab ntev ntawm astrocytes [43] . cuam tshuam mitochondrial muaj nuj nqi thiab nce ROS hauv astrocytes ua rau astrogliosis.NADPH-derived oxidative kev nyuaj siab cuam tshuam rau lub cev muaj nuj nqi ntawm astrocytes.
Ntawm NOX tsev neeg, NOX2 thiab NOX4 yog cov NOXisoforms tshaj plaws hauv CNS [43]. NOX4, tab sis tsis yog NOX2 yog qhia hauv astrocytes, thiab txawm tias tso cai qhia NOX4 tswj oxidative kev nyuaj siab hauv astrocytes [44,45].
Astrocytic RNSproduction kuj cuam tshuam rau astrocyte-derived oxidative kev nyuaj siab. Lub ntsiab NOS isoforms, suav nrog Ca2+/calmodulin-dependent neuronal NOS, endothelial NOS, thiab Ca2+-independentinducible NOS, tau pom hauv astrocytes [5,46]. Astrocytic NO ua rau astrocyte-inducedneuronal degeneration thiab Cu-Zn superoxide dismutase (SOD1) aggregation nyob rau hauv astrocytes, uas yuav induce ischemic/reperfusion CNS raug mob [47,48].
3.3. Astrocyte-Medicated Antioxidant Tiv Thaiv
Astrocytes yog cov hlwb tseem ceeb uas tswj hwm glutamate homeostasis, uas cuam tshuam ncaj qha rau qhov sib npaug ntawm oxidative kev nyuaj siab, los ntawm kev tswj hwm excitatory amino acids. Astrocytesal kuj tiv thaiv excitotoxicity los ntawm kev tso tawm cov teeb meem neurotrophic, xws li glial-cell-line-derivedneurotrophic factor (GDNF) thiab paj hlwb loj hlob (NGF), uas txhawb nqa neuronalsurvival [39,49].
Rau neuroprotection thaum oxidative kev nyuaj siab, astrocytes tsim ntau yam antioxidant molecules, xws li GSH, ascorbate, thiab vitamin E, thiab qhib ROSdetoxifying enzymes, xws li GSH S-transferase, GSH peroxidase, thioredoxin reductase, thiab catalase los txhim kho neuronal ciaj sia [26, 50, 51] ib. Tsis tas li ntawd, astrocytes koom nrog inmetal sequestration nyob rau hauv lub hlwb los tiv thaiv cov tiam ntawm dawb radicals los ntawm redox-activemetals. Astrocytes qhia txog qib siab ntawm metallothioneins thiab ceruloplasmin, uas koom nrog hauv cov hlau khi thiab kev lag luam ion [52].
Astrocytes tuaj yeem tsim cov GSH tripeptide nrog glutamate cysteine ligase thiab GSH synthetase. Astrocytes tso GSH rau hauv qhov chaw extracellular thiab neurons coj GSH ncaj qha los yog siv extracellular neuronal aminopeptidase N los tsim glycine thiab cysteine [53].
Txo kev tiv thaiv neuronal tiv thaiv oxidative raug mob tau pom hauv GSH-depleted astrocytes los ntawm kev txwv cov substrate rau GSH synthesis hauv neurons [54]. Astrocytes nce lub peev xwm los ua ke GSH los ntawm kev ua kom muaj peev xwm nce cysteine, yog li txhim kho cov nyhuv neuroprotective ntawm astrocytes tiv thaiv oxidative kev nyuaj siab [5].Lwm astrocyte antioxidant tiv thaiv mechanism yog rov ua dua ntawm ascorbate, uas tuaj yeem ncaj qha scavenge ROS thiab ua raws li cofactor rau Kev rov ua dua ntawm oxidized vitamin Eand GSH [2].
Qhov no ascorbate recycled yog siv intracellularly nyob rau hauv astrocytes thiab / los yog tso rau hauv lub extracellular qhov chaw rau neurons siv rau lawv cov antioxidant tiv thaiv mechanism. Thaum ascorbic acid nkag mus rau hauv neurons, nws inhibits kev noj qabzib thiab txhawb nqa kev thauj mus los. Ascorbic acid tswj lub astrocyte-neuron lactate shuttle [55], thiab neurons tsim glutamate, uas txhawb nqa ascorbic acid tso tawm ntawm astrocytes thaum lub sij hawm glutamatergic synaptic kev ua si [56,57].
Hauv Nrf2-Keap1-ARE txoj hauv kev, ib qho tseem ceeb endogenous antioxidant system nyob rau hauv CNS, ROS-inducible transcription factor nuclearfactor erythroid 2-txog yam 2 (Nrf2), tswj GSH system, thioredoxin system, thiab SOD [58]. Nrf2 yog tsim thiab ubiquitinated rau degradation los ntawm kev khi rau cov Kelch-zoo li ECH-koom nrog protein 1 (Keap1) nyob rau hauv basal tej yam kev mob [59].
Txawm li cas los xij, Keap1binding rau Nrf2 yog inhibited los ntawm oxidative kev nyuaj siab, thiab qhov no tso cai rau Nrf2 kom dim degradation thiab cuam tshuam nrog antioxidant teb (AREs) hauv genepromoters [60,61].
Astrocytes qhia siab dua basal thiab txhawb nqa qib ntawm ARE khi los ntawm Nrf2 dua li cov neurons [62]. Tsis tas li ntawd, tertiary butylhydroquinone (tBHQ) activates Nrf2 thiab nws downstream antioxidant enzymes, xws li txo coenzyme / quinone oxidoreductase1 (NQO1), hauv astrocytes, tab sis tsis nyob rau hauv neurons [63].
Astrocytic Nrf2 yog lub luag haujlwm tseem ceeb ntawm oxidative homeostasis raws li kev txiav txim siab los ntawm kev soj ntsuam tias Nrf2-/- astrocytes muaj cov lus teb mob hnyav dua. Tsis tas li ntawd, astrocytic dopamine D2 receptor regulates GSH synthesis ntawm Nrf2 transactivation hauv vivo [64,65].
For more information:1950477648nn@gmail.com
