Neuroprotective Thiab Immunomodulatory Action Ntawm Endocannabinoid System Hauv Neuroinflammation Part 2
Jul 11, 2024
N-acyl neurotransmitters thiab lipo amino acids sawv cev rau ib pawg cais nyob rau hauv lub endocannabinoidome, uas dais lub peev xwm rau kev txheeb xyuas cov tshiab receptor targets nyob rau hauv no system.
Acyl neurotransmitters yog ib hom neurotransmitter synthesized los ntawm glutamate thiab acetyl coenzyme A. Lawv tau dav faib rau hauv lub hlwb thiab koom nrog ntau yam txheej txheem physiological thiab pathological, xws li kev paub txog kev ua haujlwm, kev mloog, inhibition, thiab lwm yam. Nyob rau hauv xyoo tas los no, ntau dua. thiab ntau cov kev tshawb fawb tau pom tias acyl neurotransmitters muaj feem xyuam nrog kev nco.
Ua ntej, acyl neurotransmitters ua lub luag haujlwm tseem ceeb hauv kev nco. Nws koom nrog hauv kev sib kis ntawm cov neurons thiab tswj cov excitability thiab inhibition ntawm cov neurons, ua lub luag haujlwm tseem ceeb hauv kev nco, khaws cia, thiab rov qab. Cov kev tshawb fawb tau pom tias qib ntawm acyl neurotransmitters muaj kev cuam tshuam zoo nrog kev nco, thiab thaum nws qib nce, nco kuj txhim kho.
Qhov thib ob, acyl neurotransmitters zoo sib xws rau kev paub txog kev ua haujlwm. Hauv kev paub txog kev paub, acyl neurotransmitters tswj cov excitability thiab inhibition ntawm neurons los ntawm kev tswj cov calcium ion channels hauv presynaptic membrane thiab calcium ion xa mus rau hauv postsynaptic membrane, yog li cuam tshuam rau kev ua haujlwm ntawm kev txawj ntse. Cov kev tshawb fawb tau pom tias thaum qib ntawm acyl neurotransmitters txo qis, kev paub txog kev ua haujlwm kuj txo.
Tsis tas li ntawd, acyl neurotransmitters kuj muaj feem xyuam rau kev tswj kev xav. Cov kev tshawb fawb tau pom tias acyl neurotransmitters tuaj yeem cuam tshuam rau lub siab lub ntsws thiab kev tswj hwm kev xav los ntawm kev tswj cov qib neurotransmitters xws li dopamine, serotonin, thiab norepinephrine. Thaum cov theem ntawm acyl neurotransmitters nce, lub siab lub ntsws stability kuj yuav nce.
Hauv luv luv, acyl neurotransmitters zoo sib xws nrog kev nco, kev paub txog kev ua haujlwm, thiab kev tswj kev xav. Peb tuaj yeem nce qib ntawm acyl neurotransmitters los ntawm kev noj zaub mov kom zoo, kev tawm dag zog, thiab so, yog li txhawb kev txhim kho ntawm kev nco thiab kev paub txog kev ua haujlwm, thiab tswj kev xav ruaj khov thiab lub siab zoo siab. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche tuaj yeem txhim kho kev nco zoo vim Cistanche muaj cov tshuaj tiv thaiv antioxidant, tiv thaiv kev laus, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidative thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv kev noj qab haus huv. paj hlwb. Tsis tas li ntawd, Cistanche 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 muaj peev xwm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv qhov tshwm sim ntawm kev paub tsis meej thiab cov kab mob neurodegenerative.
Nyem tam sim no txhim kho lub hlwb ua haujlwm
Ntawm cov tshuaj no, N-acyldopamines yog CB1 thiab TRPV1 agonists, thaum N-acylserotonines yog TRPV1 antagonists thiab N-arachidonoyl- -aminobutyricacid (NAGABA) activates GPR92 receptor. Kev ywj pheej ntawm cov neurotransmitters dawb tom qab degradation ntawm N-acyl neurotransmitters ua rau lawv qhov kev ua haujlwm ntau dua.
3.3. Kev koom tes ntawm Endocannabinoid System hauv Teb rau Neuropathology
Endocannabinoids thiab lwm yam NAEs yog tsim los ntawm kev thov thiab ua lub luag haujlwm tseem ceeb hauv cov txheej txheem metabolic, tus cwj pwm, thiab kev tiv thaiv. Raws li kev noj qab haus huv, cov lipid mediators feem ntau muaj nyob rau hauv lub hlwb thiab tsis tshua pom muaj nyob rau hauv cov hlab ntsha thiab peripheral cov ntaub so ntswg [55].
Thaum lub sij hawm ntau yam kab mob ntawm CNS, cov ntaub ntawv ntawm eCBs thiab lawv cov congeners tau hloov pauv tseem ceeb, uas cuam tshuam nrog kev ua rau mob-mob siab, ua kom tsis zoo, thiab kev tiv thaiv neuroprotective ntawm cov tebchaw no (luam tawm hauv Table 2).
Daim duab 3. Kev taw qhia txoj hauv kev thiab kev tiv thaiv kab mob ntawm NAEs. Arachidonoylethanolamide (AEA) taw qhia los ntawm thecannabinoid receptors CB1/2, non-cannabinoid G protein-coupled receptor (GPR) 55, lub sijhawm hloov pauv receptor muaj peev xwm channel subfamily V tus tswv cuab 1 (TRPV1), thiab peroxisome proliferator-activated receptor (PPAR)- thiab.
Palmitoylethanolamide (PEA) tau pom tias inhibit fatty acid amide hydrolase (FAAH) thiab teeb liab ntawm GPR55, TRPV1, thiab PPAR-, thaum CB1/2 khi tseem muaj teeb meem.
Oleoylethanolamide (OEA) activates TRPV1 thiab PPAR-, thaum stearoylethanolamide (SEA) inhibits FAAH thiab activates PPAR-. Linoleylethanolamide (LEA) tau pom tias ua kom muaj zog TRPV1, GPR119, thiab inhibit FAAH, thaum docosahexaenoylethanolamide (DHEA) qhia txog kev ua kom GPR110.
4. Glutamate Receptor-Mediated Neurotoxicity
4.1. Glutamate ua ib qho tseem ceeb Excitatory Neurotransmitter hauv Mammals thiab Muaj Peev Xwm Neurotoxin
Ua kom cov postsynaptic neurotransmitter receptors thiab Ca{0}} influx mus rau postsynaptic davhlau ya nyob twg induce lub synthesis ntawm eCBs thiab lwm yam compounds. Qhov kev ua haujlwm-nyob ntawm kev tsim khoom ntawm eCBs yog qhov tseem ceeb rau kev tswj hwm zoo ntawm neurotransmission.
Nyob rau hauv lub hlwb mammalian, glutamate yog lub ntsiab excitatory neurotransmitter implicatedin kev kawm thiab nco tsim. Glutamatergic neurotransmission mediates synapticplasticity, uas yog ionotropic thiab metabotropic (mGluRs) glutamate receptors ua lub luag haujlwm tseem ceeb.
Nyob nruab nrab ntawm lub quantal neurotransmitter tso tawm, theem ntawm glutamate nyob rau hauv lub synaptic cleft yog kwv yees li.<1 µM. This low basal level is maintained by rapid reuptake of glutamate from the extracellular space into the cytosol by high-affinity glutamate transporters EAATs (excitatory amino acid transporters). EAATs are localized on neurons (primarily EAAT4 and EAAT3 (EAAC1, Excitatory Amino Acid Carrier)) and astrocytes (primarily glutamate transporter GLT-1 and glutamate-aspartate transporter GLAST), and co-transport one molecule of L-glutamate (or L-/D-aspartate) with 3Na+ and 1H+ in exchange of 1K+ [66].
Kev vam khom ntawm qhov kev thauj mus los no ntawm Na + thiab K + gradients thoob plaws plasma membrane ua rau nws muaj kev cuam tshuam rau ATP depletion nrog kev cuam tshuam tom qab ntawm glutamate uptake lossis thim rov qab ntawm cov thauj khoom [67].
Lwm qhov cuam tshuam rau kev ua haujlwm ntawm glutamate tshem tawm los ntawm synaptic cleft yog kev txhais lus tswj ntawm EAATs lossis kev hloov pauv tom qab kev hloov pauv ntawm cov khoom thauj khoom, uas cuam tshuam rau qib ntawm cov neeg thauj khoom nquag. Glutamate yog ntxiv rau hauv cov synaptic vesicles viavesicular glutamate transporters VGLUTs siv ∆µH + gradient.
Xav txog qhov siab zog-dependent compartmentalization ntawm glutamate thiab nws gradient hla lub synaptic bouton, piv txwv li, los ntawm synaptic vesicles (~ 200 mM [68]) mus rau thesynaptic cleft (<1 µM between release events, around 1 mM during the peak of SV release [69]), any factors affecting the efficiency of high-affinity glutamate uptake represent a potential risk of neurotoxic neuronal damage.
Cov kab mob pathophysiological nyob rau hauv lub sij hawm ntev glutamate nce nyob rau hauv lub synaptic cleft thiab extrasynaptic glutamate spilloverare traumatic lub hlwb raug mob, ischemia, thiab lwm yam ua rau hypoxia, mob stroke, thiab oxidativestress ua rau txoj kev hloov ntawm qhov tseem ceeb ntawm EAATs mus rau lub rov qab hom whenglutamate yog. tso tawm los ntawm cytosol mus rau qhov chaw extracellular. Glutamate-mediated neurotoxicity originates los ntawm overstimulation ntawm ionotropic glutamate receptors, feem ntau N-methyl-D-aspartate (NMDA) receptors, thiab loj Ca2+ flux mus rau postsynaptic davhlau ya nyob twg.
High extracellular concentrations ntawm glutamate ua rau lub sij hawm ntev co-activation ofsynaptic thiab extrasynaptic (localized mus rau non-synaptic sites) NMDA receptors, glutamate-mediated neurotoxicity [70], thiab koom nyob rau hauv lub pathogenesis ntawm Alzheimer's kab mob, amyotrophic laterals (AL) sclerosis. , thiab Huntington tus kab mob.Vim Ca2+ permeability thiab siab affinity rau glutamate, NMDA receptors yog ib tug thawj molecular lub hom phiaj implicated nyob rau hauv lub pathogenesis ntawm excitotoxicity.
Ntawm qhov muaj peev xwm so membrane, tam sim no los ntawm cov channel NMDA receptors yuav luag tag nrho los ntawm Mg 2+ tiv thaiv kev coj ua ntawm cov stimuli. Thaum lub sij hawm quantal neurotransmitter tso tawm, ob qho xwm txheej rau Ca2+ influx los ntawm NMDA receptors tau ntsib: * glutamate concentrations nce sai, thiab ** depolarization ntawm synaptic membranes tshem tawm Mg2+ thaiv los ntawm NMDA receptor channels.
Therapeutic concentrations (1–10 µM) ntawm NMDA receptor antagonist memantine, siv rau kev kho mob ntawm Alzheimer'sdisease, nyiam tshaj thaiv cov extrasynaptic es tsis yog synaptic tam sim no los ntawm NMDAreceptors hauv tib lub neuron [71].
Hom kev ua ntawm memantine ua rau muaj txiaj ntsig zoo tiv thaiv ntau dhau ntawm extrasynaptic NMDA receptor stimulation, nrog cov nyhuv tsawg dua ntawm NMDA receptor-mediated synaptic kev ua si thaum glutamate nce siab rau milliseconds [72].
Raws li qhov tseem ceeb ntawm kev nce qib ntawm intracellular Ca2+ qib, vesicular glutamate tso tawm yog lwm yam uas ua rau kom nce ntxiv ntawm cellular glutamate concentration thiab excitotoxicdamage.
Hauv cov nas thiab nas, cov kab mob ischemic, ua raws li kev tso tawm ntawm axonal vesicularglutamate mus rau hauv qhov chaw peri-axonal hauv qab myelin sheath, ua rau kom muaj myelinicGluN2C / D-muaj NMDA receptors [73], uas feem ntau yog extrasynaptic [74].
4.2. Excitotoxicity raws li qhov yuav tsum tau ua ua ntej thiab qhov tshwm sim ntawm Neuroinflammation thiab Neurodegeneration
Vim muaj peev xwm ntawm Ca2+ los ua kom muaj ntau yam enzymes, glutamate receptor-mediatedexcitotoxicity provokes necrotic thiab apoptotic neuronal tuag. Qhov loj heev influx ntawm Ca2+ overloads lub intracellular buffer systems rau no ion, provokes mitochondrial dysfunction, thiab ua kom ib tug ntau yam ntawm proteases, xws li caspases thiab calpain, ua rau tom qab degradation ntawm cov khoom ntawm cov neuronal tso tawm cytoskeleton thiab cov kab mob. Cov xwm txheej.Ib qho piv txwv ntawm kev koom tes ntawm ECS hauv kev sib tham hauv xov tooj ntawm tes yog kev sib txuas ua haujlwm ntawm microglia thiab synapses thaum lub sijhawm ua haujlwm synaptic li qub thiab raug mob excitotoxic.
Raws li tau hais dhau los, microglia yog qhov tseem ceeb ntawm de novo-tsim AEA thiab 2-AG nyob rau hauv cov xwm txheej basal thiab thaum lub sij hawm neuroinflamation [75–77]; Txawm li cas los xij, daim ntawv thov glutamate siab ua rau muaj qhov tseem ceeb 2-AG overproduction hauv neurons [76,78].
Nyob rau hauv cov xwm txheej no, cov neuronal ntau lawm ntawm AEAincreases tsuas yog me ntsis, thaum zus tau tej cov ob putative endocannabinoids, homogamma-linolenylethanolamide thiab docosatetraenylethanolamide tseem unchanged [76].
LPS-induced systemic o nyob rau hauv nas yog nrog los ntawm kev nce qib ntawm basal glutamate nyob rau hauv prefrontal cortex [47]. Qhov siab glutamate tuaj yeem tshwm sim los ntawm ob qho tib si kev mob tshwm sim los ntawm kev txo qis hauv kev nqus, thiab neuronal thiab non-neuronal (los ntawm astrocytes thiab microglia) glutamate tso tawm. Glutamate txaus nyiam kev sib koom tes ntawm qhov chaw nruab nrab ntawm dendritic spines thiab ramified microglial hlwb thiab induces microglial processextension rau neurons (Daim duab 4).
2-AG induces chemokinesis (random motion nce los ntawm ib tug tshuaj stimulus) thiab chemotaxis, (qhia cell tsiv teb tsaws raws ib tug chemicalgradient) nyob rau hauv microglial hlwb [76,79].
Nyob rau hauv txoj kab nrog qhov no, activated microglia nthuav qhia CB2 receptors ntawm cov ntug ntawm lawv cov motile protrusions [76]. Arachidonylcyclopropylamide (ACPA)-vim kev tsiv teb tsaws ntawm BV-2 microglia tuaj yeem raug thaiv los ntawm cov neeg tiv thaiv CB2 SR145528 [80]. Ib yam li ntawd, cov lus teb ntawm kev tsiv teb tsaws ntawm 2-AG thiab thesynthetic cannabinoid CP 55,940 tau cuam tshuam los ntawm CB2 receptor antagonism [76,79].
Wehypothesize tias eCBs tso tawm ntawm qhov chaw ntawm synaptic kev ua si (los yog raug mob) yuav ua raws li chemoattractants mus nrhiav microglia nyob rau hauv ib tug CB2- raws li nyob rau hauv, mus rau neuroinflammatory lesion sites. Ntxiv mus, nyob rau hauv organotypic hippocampal daim kab lis kev cai, 2-AG mediated neuroprotection tiv thaiv NMDA-induced excitotoxicity los ntawm kev ua kom meej meej ntawm txawv txav-cannabidiol (ABN-CBD)-rhiab heev receptor, putative GPR18, ntawm microglial hlwb [81].
cannabinoids tsim nyob rau hauv glutamatergic synapse nyob rau hauv excitotoxic tej yam kev mob nyiam microglial hlwb mus rau qhov sib thooj rau cov leeg. Los ntawm kev siv cov tshuaj tiv thaiv kab mob los yog kev muaj sia nyob phenotype microglia feem ntau txhais txoj hmoo ntawm cov hlwb raug mob thiab txha nraub qaum. eCB signaling txo qhov presynaptic neurotransmitter tso tawm, txhawb lub voj voog glutamate-glutamine, thiab sib npaug glutamate / GABAergic kis tau tus mob.
AMPA, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; BDNF, hlwb-derived neurotrophic yam; CB, cannabinoid receptor; EAATs, excitatory amino acid transporters; eCBs, endocannabinoids; ER, endoplasmic reticulum; GDNF, glial cell line-derived neurotrophic yam; Gln, glutamine; Glu, glutamic acid; IFN, interferon-gamma; IL, interleukin; mGluRs, metabotropic glutamate receptors; NGF, paj hlwb growthfactor; NMDA, N-methyl-D-aspartate receptor; Tsis yog, nitrogen monoxide; PGD2, prostaglandin D2; QUIN, quinolinic acid; Daim duab 4.
Kev txhim kho ntawm synaptic dysfunction thiab kev koom tes ntawm ECS hauv cov lus teb neuroprotective. Endocannabinoids tsim nyob rau hauv glutamatergic synapse nyob rau hauv excitotoxic tej yam kev mob nyiam microglial hlwb mus rau qhov sib thooj rau cov leeg.
Los ntawm kev siv cov tshuaj tiv thaiv kab mob los yog kev muaj sia nyob phenotype microglia feem ntau txhais txoj hmoo ntawm cov hlwb raug mob thiab txha nraub qaum. eCB signaling txo qhov presynaptic neurotransmitter tso tawm, txhawb lub glutamate-glutaminecycle, thiab sib npaug glutamate / GABAergic kis tau tus mob.
AMPA, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acidreceptor; BDNF, hlwb-derived neurotrophic yam; CB, cannabinoid receptor; EAATs, excitatory amino acid transporters; eCBs, endocannabinoids; ER, endoplasmic reticulum; GDNF, glial cell line-derived neurotrophic yam; Gln, glutamine; Glu, glutamic acid; IFN, interferon-gamma; IL, interleukin; mGluRs, metabotropic glutamate receptors; NGF, nervegrowth yam; NMDA, N-methyl-D-aspartate receptor; Tsis yog, nitrogen monoxide; PGD2, prostaglandin D2; QUIN, quinolinicacid; ROS, reactive oxygen hom; TGF, transforming kev loj hlob factor-beta; TNF, qog necrosis factor alpha; VGCC, voltage-gated calcium channels.
Muaj kev ua haujlwm-nyob ntawm kev hloov kho ntawm microglia-synapse hu hauv vivo. Lub paj hlwb ischemic yog tus cwj pwm los ntawm lub sijhawm sib cuag ntev heev ntawm microglialprocesses thiab cov qauv synaptic thiab qhwv cov txheej txheem microglial nyob ib ncig ntawm lub synapse, ua raws li kev ploj ntawm presynaptic boutons [82].
Ib qho ntawm cov txheej txheem uas microglia tshem tawm presynaptic boutons thiab axons istrogocytosis [83], txheej txheem piav qhia hauv lub cev tiv thaiv kab mob uas tsis yog-apoptotic mechanism rau kev ntes ntawm daim nyias nyias uas txawv ntawm phagocytosis thiab cuam tshuam nrog kev cuam tshuam thiab tshem tawm cov txheej txheem cellular loj dua 1. pwm [84].
Nyob rau hauv tus nas qauv ntawm cortical ntau yam sclerosis nyob rau hauv vivo imaging qhia tau hais tias cortical o cuam tshuam kev ua haujlwm hauv Circuit Court, uas sib koom ua ke nrog kev dav, tab sis thim rov qab, poob ntawm dendriticspines. Nyob rau hauv cov xwm txheej no, spines displaying zos calcium accumululations raug tshem tawm los ntawm invading macrophages los yog nyob rau hauv-activated microglia [85].
Kev ua kom mob microglia nrog kev tso tawm ntawm glutamate, quinolinicacid, proinflammatory cytokines (IL-1, TNF-, IL-2, IL-6), chemokines-macrophageinflammatory protein-1 (MIP-1 ) thiab monocyte chemoattractant protein-1 (MCP-1), thiab dawb arachidonic acid.
Quinolinic acid tsim tshwj xeeb hauv cov tshuab ua kom muaj microglia thiab macrophages, yog NMDA receptor agonist thiab kho cov excitotoxicity thaum lub sij hawm tiv thaiv kab mob.
Los ntawm kev ua kom tsis muaj zog ntawm cytoskeleton hauv astrocytes thiab endothelial hlwb, quinolinic acid txo qhov kev ncaj ncees ntawm cov hlab ntsha thiab ua kom cov BBB impermeable quinolinic acid los ntawm periphery [86].
Ua excitotoxic molecules thiab proinflammatory cytokines intensify dawb radical tiam thiab lipid peroxidation, uas provoke mitochondrial tsis ua hauj lwm thiab exacerbate excitotoxicity.
Microglia feem ntau txhais txoj hmoo ntawm kev puas tsuaj synaptic hu thiab hlwb thiab txhawb kev daws teeb meem ntawm neuroinflammation thiab rov tsim dua los ntawm kev tso tawm lub hlwb-derived neurotrophic factor (BDNF) thiab cytokines nrog dual (pro- thiab anti-inflammatory) muaj peev xwm, zoo li TGF- thiab IL{{4. }}.
5. Lub luag hauj lwm ntawm Retrograde Endocannabinoid Signaling nyob rau hauv Tuning ntawm SynapticStrength
5.1. Synaptic Plasticity hauv Glutamatergic Synapses
Thaum glutamate qib nce mus txog qee qhov concentration hauv cov synaptic cleft, nws khi rau AMPA receptors thiab induces Na + influx, uas tau sau npe ua excitatory postsynapticpotentials (EPSP) ntawm qee qhov amplitudes.
Vim muaj cov GluR2 subunit, lawv feem ntau ntawm AMPA receptors hauv CNS yog impermeable rau Ca2+ [87] thiab postsynapticCa2+ influx tshwm sim los ntawm glutamate feem ntau yog kho los ntawm NMDA receptors. Kev nkag mus ntawm Ca2+ los ntawm NMDA receptor channels ua kom muaj ntau yam ntawm kinases, feem ntau Ca2+/calmodulin-dependent protein kinase II (CaMKII) [88,89], uas nyob rau hauv lem activatesRho GTPases, Cdc42, and RhoA [90].
Qhov no reorganizes postsynaptic ntom ntawm * remodeling ntawm actin cytoskeleton thiab ncua sij hawm (~ 5 min) o ntawm tus txha nraub qaum (Daim duab 5); ** txhim kho kev lag luam ntawm AMPA receptors rau cov chaw tom qab synaptic vim lawv qhov kev faib tawm los ntawm kev rov ua dua endosome rau cov plasma membrane [91,92], thiab *** nce ib-channel conductance ntawm AMPA receptors los ntawm phosphorylation ncaj qha [93].
Synaptic recruitment ntawm Ca2+-permeable AMPA receptors ntawm CaMKI kuj tau hais kom pab txhawb rau kev taw qhia txoj hauv kev uas tsav txha nraub qaum los ntawm actin polymerization [94].
Yog li, tom qab rov ua dua lub voj voog, qhov amplitude ntawm evokedEPSC nce, piv txwv li, yog potentiated (ntev ntev potentiation, LTP). Cov nyhuv no yog ib txwm muaj kev cuam tshuam rau cov neurotransmission thiab tseem nyob hauv cov synapses nyob ntawm hom kev txhawb nqa.In sib piv, kev nyuaj siab mus sij hawm ntev (LTD) yog ib qho kev poob mus ntev hauv kev ua haujlwm ntawm kev sib kis ntawm synaptic vim qhov txo qis hauv postsynaptic receptor ntom thiab / orpresynaptic. neurotransmitter tso tawm. Thaum rau kev txhim kho LTP, qhov ua kom muaj qee yam protein kinases yog qhov tseem ceeb, LTD induction yog nyob ntawm cov protein phosphataseactivity thiab lub hom phiaj dephosphorylation.
Ntev 1 Hz stimulation ua rau Ca2+ nce thiab calcineulin-dependent activation ntawm calcineurin (protein phosphatase 2B, PP2B) [95], whichvia serine/threonine protein phosphatase PP1 lossis PP2A, ua rau [dephosphory] receptors. , txo qis ntawm lawv txoj kev coj ua channel, thiab raug ntes ntawm lawv cov khoom siv rov ua dua tshiab [97].
Dephosphorylation ntawm transcription factor cAMP teb elementbinding protein (CREB) nyob rau hauv hippocampal cheeb tsam CA1 nyob rau hauv vivo yog pom zoo kom yog ib tug ntawm cov mechanisms los ntawm uas cov protein phosphatase pab rau lub prolongedmaintenance LTD [98].
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