Carboxypeptidase E Conditional Knockout Mice Qhia Txog Kev Kawm Thiab Kev Nco Tsis Txaus Thiab Neurodegeneration Part 2
Nov 23, 2023
Nissl thiab immunofluorescence staining
Tsiaj txhu tau perfused nrog 4% paraformaldehyde, thiab cov seem khov ntawm cov ntaub so ntswg tau txais. Cov ntaub so ntswg ntawm lub hlwb tau muab faib ua 30 µmsections rau Nissl, doublecortin (DCX), CPE, thiab MAP2 staining.
Nyob rau hauv xyoo tas los no, nrog kev txhim kho txuas ntxiv ntawm kev kho mob thev naus laus zis, ntau thiab ntau tus neeg tau pib mob siab rau yuav ua li cas txhawm rau txhim kho lawv lub cim xeeb kom tiv nrog kev nce zuj zus thiab nrawm ntawm lub neej. Nyob rau tib lub sijhawm, doublecortin tau maj mam dhau los ua ib lub ntsiab lus kub ntawm kev sib tham.
Yog li dab tsi yog doublecortin? Doublecortin yog ib yam khoom hauv lub hlwb uas ua lub luag haujlwm tseem ceeb hauv kev txhawb nqa thiab tswj kev nco. Nws yog tsuas yog faib nyob rau hauv lub synapses ntawm neurons nyob rau hauv lub hlwb. Nws tuaj yeem tswj hwm qhov excitability ntawm neurons thiab txhawb kev sib kis ntawm cov ntaub ntawv ntawm neurons, yog li txhim kho tib neeg kev txawj ntse thiab kev nco.
Qee qhov kev tshawb fawb tau pom tias muaj kev sib raug zoo ntawm cov qib doublecortin thiab kev nco. Piv txwv li, qee cov neeg laus muaj qhov txo qis ntawm doublecortin, thiab tib lub sijhawm, kev nco poob qis. Tsis tas li ntawd xwb, qee cov kab mob neurological, xws li Alzheimer's disease thiab Parkinson's disease, kuj tseem cuam tshuam nrog kev txo qis dua ob npaug.
Txawm li cas los xij, tsis txhob quav ntsej tias doublecortin tsis yog panacea. Nws tsuas tuaj yeem pab tib neeg txhim kho lawv lub cim xeeb rau qee qhov, tab sis nws tsis tuaj yeem daws txhua yam teeb meem nco. Tsis tas li ntawd, txawm hais tias qee qhov kev sim tau pom tias qhov kev txhawb nqa doublecortin tuaj yeem txhim kho kev txawj ntse thiab kev txawj ntse, cov kev sim no tsis tuaj yeem ua pov thawj tias doublecortin tuaj yeem txhim kho tib neeg kev txawj ntse.
Yog li ntawd, yog tias koj xav txhim kho koj lub cim xeeb, nws tsis txaus los ntxiv doublecortin ib leeg. Ntau lwm yam tuaj yeem pab txhim kho kev nco. Piv txwv li, kev tawm dag zog ntau dua, tswj tus cwj pwm zoo, ua haujlwm tsis tu ncua thiab so, thiab lwm yam tuaj yeem pab tib neeg txhim kho lawv txoj kev nco.
Nyob rau hauv luv luv, muaj tseeb muaj ib tug tej yam kev sib raug zoo ntawm doublecortin thiab nco, tab sis peb yuav tsum tsis txhob tso siab heev cia siab rau ntawm doublecortin. Qhov no tsis tau txhais hais tias peb yuav tsum tsis txhob mloog rau doublecortin. Ntawm qhov tsis sib xws, peb yuav tsum nkag siab nws lub luag haujlwm kom nkag siab ntau ntxiv kom tswj tau thiab txhim kho peb lub cev kev noj qab haus huv. Cia peb ua haujlwm ua ke los txhim kho peb lub cim xeeb! Nws pom tau tias peb yuav tsum txhim kho peb lub cim xeeb. Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola tseem tuaj yeem tswj hwm qhov sib npaug ntawm cov neurotransmitters, xws li nce qib ntawm acetylcholine thiab kev loj hlob. Cov khoom no tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, cov nqaij kuj tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov as-ham txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.
Nyem paub cov tshuaj ntxiv los txhawb kev nco
Luav antiDCX antibody (1: 1000; Cell Signaling Technology, Boston, USA, 4604S), nas anti-CPE antibody (1: 1000; BD bioscience, New Jersey, USA, 610758), luav anti-GFAP antibody (1: 200; Cell Signaling Technology, 80788), thiab luav anti-MAP2 antibody (1: 1000; Cell Signaling Technology, 8707) tau siv rau immunofluorescence.
Cov tshuaj tiv thaiv thib ob yog Alexa Fluor 594 tshis los tiv thaiv nas thib ob antibody (1: 1000; Invitrogen, Carlsbad, CA, 11005) lossis Alexa Fluor 594 tshis los tiv thaiv luav secondaryantibody (1: 1000; Invitrogen, 11012). Qhov txheeb ze fluorescence siv ntawm MAP2 thiab GFAP hauv hippocampal Sub thiab dmPFC ntawm × 100 magnification tau suav nrog siv ImageJ software (National Institutesof Health, USA).
Western blotting
Hippocampal thiab PFC cov ntaub so ntswg tau npaj raws li tau piav qhia yav dhau los [22].Bands tau txheeb xyuas siv ImageJ software. Cov qauv protein tau khiav ntawm 10% SDS-polyacrylamide gel electrophoresis gels thiab pauv mus rau ontonitrocellulose membranes (0.22 μm; Millipore, Billerica, MA, USA).
Tom qab thaiv nrog 5% cov mis nyuj uas tsis muaj rog, daim nyias nyias tau raug tshem tawm nrog cov tshuaj tiv thaiv kab mob tiv thaiv nas anti- -actin antibody (1: 1000, CST, 4967S), nas anti-CPEantibody (1: 1000; BD bioscience, 610758), nas anti- BDNF antibody (1:600, Abcam, UK, ab108319), luav anti-p-TrkB antibody (1: 1000; Boster, Wuhan, Tuam Tshoj, BM4437), luav anti-AKT (1: 2000, Cell Signaling Technology, 4691S) , thiab anti-p-AKT (1: 2000, Cell Signaling Technology, 23430S) hmo ntuj ntawm 4 degree .
Tom qab ntxuav, cov membranes tau incubated nrog anti-nas los yog anti-luav cov tshuaj tiv thaiv IgG rau 1 h ntawm chav tsev kub. Cov qib qhia protein rau txhua tus qauv yog normalized rau -actin.
Kev txheeb cais
Cov ntaub ntawv tau txheeb xyuas los ntawm ib txoj kev tsom xam ntawm qhov sib txawv (ANOVA) rau ntau pawg. Kev tshuaj xyuas tau ua tiav siv GraphPad Prism 8.0 (PrismGraphPad software). Tag nrho cov nqi yog qhia los ntawm txhais tau tias ± standarderrors (SEM). P < 0.05 tau suav tias yog qhov tseem ceeb.
TSEEM CEEB
Kev soj ntsuam ntawm lub cev qhov hnyav thiab qabzib hauv plasma
Cov nas uas muaj hnub nyoog 1-20 lub lis piam tau siv los ntsuas lub cev qhov hnyav thiab cov piam thaj hauv ntshav (Fig. 1a). Cov txiaj ntsig tau pom tias tsis muaj qhov sib txawv ntawm lub cev hnyav ntawm WT, CPEflox/−, thiab CPEflox/flox nas. Kev yoo mov thiab cov metabolism hauv cov piam thaj hauv ntshav tau raug ntsuas thaum muaj hnub nyoog 10 lub lis piam (Fig. 1b). Peb pom qhov sib txawv nogenotype ntawm WT, CPEflox/−, thiab CPEflox/flox tsiaj.
Kev kawm thiab kev nco poob hauv CPEflox/flox nas
Los ntawm qhov kev ntsuam xyuas qhib, peb pom tias tsis muaj qhov sib txawv ntawm txhua pawg genotype rau qhov kev ncua deb mus rau hauv qhov chaw qhib (Fig. 2a). Qhov no qhia tau hais tias kev tswj hwm tus kheej thiab nug tus cwj pwm ntawm CPEflox / flox nas tsis cuam tshuam. Rau kev kawm thiab kev nco hauv cov nas, peb siv qhov kev kuaj pom cov khoom (Daim duab 2b).Peb pom tias CPEflox / flox nas siv sijhawm tsawg dua ntawm cov khoom tshiab dua li WT nas. Y-maze thiab FCT-lub sij hawm luv luv tau muab coj los soj ntsuam lub sij hawm luv luv hauv nas (Fig. 2c–e).
Hauv kev sim Y-maze, WT thiab CPEflox / - nas siv sijhawm ntau dua hauv cov ntawv sau tshiab dua li CPEflox / flox nas. Rau lub sijhawm luv luv FCT, qhov kev khaws cia luv luv ntawm CPEflox / flox nas yog qhov phem tshaj ntawm WT thiab CPEflox / - nas. Rau kev khaws cia ntev ntev (Daim duab 2f), qhov kev ntsuam xyuas kev ntshai qhia tau hais tias WT thiab CPEflox / - nas muaj qhov cim xeeb zoo dua rau ko taw poob siab dua li CPEflox / flox nas.
CPEflox/flox nas qhia subiculum (Sub) degeneration
Peb siv western blotting los ua tus yam ntxwv ntawm CPElevels nyob rau hauv lub hippocampus piv nrog lub internal controlprotein -actin (Fig. 3a, b). Cov txiaj ntsig tau pom tias CPE protein nyob rau hauv hippocampus ntawm CPEflox / flox nas poob qis heev. Tom qab qhov kev ntxhov siab, lub cheeb tsam ntawm CPEflox / flox nas tau degenerated tag nrho, tab sis tsis ua ntej hnav, thaum lub hippocampal tsim ntawm WT nas tsis zoo (Fig. 3c).
CPEflox / flox nas qhia qhov txo qis hauv GFAP thiab MAP2 kev siv thiab TrkB teeb liab hauv hippocampus
Peb tau soj ntsuam qhov kev qhia ntawm Akt/mTOR-mediated BDNF/TrkBpathway-related proteins. Western blot tsom xam ntawm BDNF proteins qhia tau hais tias piv nrog WT nas, cov ntsiab lus ntawm BDNFprotein nyob rau hauv lub hippocampus ntawm CPEflox / flox nas pom qhov sib npaug piv nrog WT thiab CPEflox / - nas (Fig. 4a, b). P-TrkB protein tau txo qis hauv CPEflox/flox nas piv nrog WT thiab CPEflox/− nas (Fig. 4a, c).
Cov txiaj ntsig tau qhia tias CPEflox / flox nas pom qhov txo qis hauv hippocampal phosphorylated Akt thiab phosphorylated mTOR qhia piv nrog WT nas (Fig. 4a, d, e). Cov txiaj ntsig ntawm immunofluorescence pom tias txo qis CPE qhia hauv hippocampal Sub (Fig. 4f, g). Weused anti-MAP2 immunostaining los qhia MAP2 siv nyob rau hauv lub hippocampal Sub thiab hilus cheeb tsam (Fig. 4f).
Cov txiaj ntsig ntawm immunofluorescence tau pom tias MAP2 kev siv qis hauv Sub andhilus ntawm CPEflox/flox nas tab sis tsis nyob hauv WT thiab CPEflox/- nas (Fig. 4f, h, i). Tsis tas li ntawd, DCX immunostaining pom tias neurogenesis hauv DG ntawm hippocampus hauv CPEflox / - nas zoo ib yam li cov nas hauv WT tab sis txo qis hauv CPEflox / flox nas (Fig. 4f, j). GFAP kev siv zog hauv hippocampal Sub tau qis dua hauv CPEflox / flox nas dua li WT nas (Fig. 4f, k).
CPEflox / flox nas qhia qhov txo qis hauv GFAP thiab MAP2 kev siv zog hauv dmPFC
Peb siv western blotting los qhia qhov qhia txog CPElevels hauv dmPFC piv nrog -actin (Fig. 5a, b). Cov txiaj ntsig tau pom tias CPE protein nyob hauv dmPFC ntawm CPEflox / flox nas tau txo qis. Tom qab qhov kev ntxhov siab, cov txiaj ntsig ntawm immunofluorescence pom tias MAP2 kev siv zog hauv dmPFCCPEflox / flox nas tab sis tsis nyob hauv WT nas (Fig. 5c, d). Tsis tas li ntawd, GFAPintensity hauv dmPFC tau qis dua hauv CPEflox / flox micethan hauv WT nas (Fig. 5c, e).
Kev sib tham
Nyob rau hauv txoj kev tshawb no, peb tsim ib tug CPE-cKO nas los kawm qhov poob-of-function phenotype ntawm CPE nyob rau hauv neurons ntawm lub hlwb. Ib qho kev tshawb fawb yav dhau los tau pom tias CPE-KO nas tsim kev rog thiab ntshav qab zib thiab hnyav dua thaum muaj hnub nyoog 8 lub lis piam dua WT nas [5]. Peb qhov kev ntsuas tau pom tias tsis muaj qhov hloov pauv loj hauv lub cev hnyav, qib ntshav qabzib hauv cov ntshav, thiab cov piam thaj kam rau ntawm CPEflox / flox nas piv rau WT nas.
Cov kev tshawb fawb txog kev coj cwj pwm tau txiav txim siab tias qhov kev ntxhov siab rau CPEflox / flox nas impairedlearning thiab nco. Tsis tas li ntawd, kev ntxhov siab thiab txo qis CPEexpression ua rau hippocampal Sub-degeneration, diminishedneurogenesis hauv DG, thiab txo qis neuronal ntom hauv thehippocampal Sub thiab dmPFC.
CPE yog prohormone-processing enzyme uas txheej txheem prohormone, uas cleaves C-terminal yooj yim residue los ntawm precursor ntawm enkephalin los tsim enkephalin [23]. Raws li aneuroprotective yam, CPE plays lub luag haujlwm tseem ceeb hauv embryonicand postnatal hlwb kev loj hlob [24].
Ib daim ntawv tshaj tawm qhia tias kev hloov pauv tsis zoo ntawm homozygous hauv CPE noob yog txuam nrog kev kho mob phenotypes uas muaj kev rog, kev txawj ntse, thiab hypogonadism [2]. CPEfat / rog nas qhia qhov txo qis ntawm CPE thiab nce qib ntawm proinsulin, uas txhawb nqa lub luag haujlwm ntawm CPE hauv insulin dysregulation [25].Spontaneous point hloov hauv CPE txo cov kev ua enzyme, ua rau muaj kev rog hnyav [4]. Cov nas CPE-KO mob ntshav qab zib mellitus, thiab cov nas no muaj cov piam thaj ntau thaum muaj hnub nyoog 8-10 lub lis piam.
Cov qib qabzib siab tau khaws cia rau kwv yees li 2 lub hlis thiab tom qab ntawd pib txo qis, qhia txog kev rov qab los ntshav qab zib phenotype [26]. Peb txoj kev tshawb fawb pom tau tias tsis muaj qhov sib txawv ntawm CPEflox / flox thiab WT nas nyob rau hauv cov qib plasmaglucose thiab qabzib kam rau lub hnub nyoog 10 lub lis piam. CPE-KOmice pib nce qhov hnyav los ntawm kwv yees li 4 lub lis piam ntawm hnub nyoog, thiab lawv hnyav dua li WT litters los ntawm 8 lub lis piam [27]. Nws tau raug pom tias CPE-KO nas qhia tias noj zaub mov ntau ntxiv.
Kev noj ntau ntxiv yog qhov tshwm sim ntawm cov teeb meem tsis raug tswj kev noj zaub mov noj, nrog rau qhov sib npaug ntawm orexigenic andanorexic neuropeptides hauv hypothalamus [5]. Kev ua kom zoo ntawm cov neuropeptides no yuav tsum muaj kev thauj mus los thiab ua tiav ntawm cov neuropeptides, uas CPE ua lub luag haujlwm tseem ceeb [28].
Peb tau sau lub cev qhov hnyav ntawm micef los ntawm 1 mus rau 20 lub lis piam, thiab cov txiaj ntsig tau pom tias cov CPEin neurons tshem tawm tsis cuam tshuam rau lub cev hnyav. Hauv peb txoj kev tshawb fawb, CPE-cKO tsis hloov qhov hnyav lossis noj qabzib. Tej zaum nws yuav yog qhov kev txiav txim siab ntawm CPE hauv cov neurons tsis cuam tshuam rau cov teeb meem tswj kev noj zaub mov. Yog li ntawd, xws li CPE-cKO nas yog cov qauv zoo rau kev kawm qhov poob-ntawm-kev ua haujlwm phenotype ntawm CPEin neurons ntawm lub hlwb.
CPE ua si ntau lub luag haujlwm hauv lub hauv nruab nrab lub paj hlwb, nrog rau kev tswj hwm kev paub txog kev ua haujlwm zoo, tsim nyog neuronalstructure, thiab neuronal ciaj sia [3]. CPE tau xav tias ua lub luag haujlwm hauv cell ua cov protein ua ntej. Nws kuj muaj neuroprotectiveactivity, ywj siab ntawm nws cov enzyme kev ua, ua extracellularlyas ib tug neurotrophic yam [25]. Lub luag haujlwm tshiab ntawm CPE hauv kev txhim kho neurodevelopment thiab cov ceg ntawm cov dendrites ze ze tau pom, uas yog qhov tsim nyog rau kev tsiv teb tsaws thiab dendrogenesis ntawm cortical neurons [29]. CPE-KO nas nyob rau hauv kev ntxhov siab tsis muaj kev ua CPE muaj ntau yam kev coj cwj pwm txawv txav, suav nrog kev kawm thiab kev nco tsis txaus [30]. Cov kev tshawb fawb yav dhau los tau ntsuas cov txheej txheem kev kawm thiab kev nco thaum cov tsiaj muaj hnub nyoog kwv yees li 2 lub hlis thaum qhov hnyav ntawm micehad nyuam qhuav pib sib txawv [31].
Kev ntxhov siab tau lees paub los cuam tshuam rau hippocampus atvarious qib ntawm kev tsom xam [32]. Kev coj cwj pwm, kev tshawb fawb tau pom tias kev ntxhov siab feem ntau cuam tshuam ntau yam kev kawm hippocampus-raws li kev kawm thiab nco ua haujlwm [20]. Neurally, cov kev tshawb fawb tsiaj tau qhia tias kev ntxhov siab hloov pauv cov synaptic plasticity thiab firingproperties ntawm hippocampal neurons [33]. Raws li cov qauv, cov kev tshawb fawb tau pom tias kev ntxhov siab hloov pauv neuronal morphology suppresses cov khoom tshiab ntawm cov paj hlwb hauv cov dentate gyrus, thiab txo cov ntim hippocampal [34]. Peb tau ua qhov kev lees paub, Y tshawb nrhiav, thiab kev ntsuas kev ntshai ntawm CPEflox / flox nas thaum muaj hnub nyoog 10 lub lis piam. Rau kev paub txog cov khoom, WT nas pom qhov tsis txaus siab nyiam rau cov khoom tshiab.
Hauv qhov sib piv, CPEflox / flox micefailed los qhia qhov nyiam rau txhua yam khoom thaum lub sijhawm no.Y tshawb nrhiav tau siv los ntsuas qhov kev nco luv luv ntawm nas.WT nas xav paub ntau dua li CPEflox / flox nas mus tshawb txog thaj chaw uas tsis tau mus xyuas ua ntej. . Tsis tas li ntawd, qhov kev ntsuam xyuas kev ntshai raug siv los ntsuas qhov luv- thiab ntev kev nco nco.
WTmice tau txais txiaj ntsig zoo dua hauv kev paub txog cov kev mob tshwm sim ntau dua li CPEflox / flox nas. Nws yuav tsum raug sau tseg tias CPE KO micewere tsis ntev los no tau tsim nyob rau hauv Pomc txhawb nqa, uas tshem tawm cov hlwb uas qhia txog proopiomelanocortin. Cov kab mob CPE-cKO no tau qhia txog lub cev ib txwm muaj, tus cwj pwm, thiab qib ntawm neuropeptides[35]. Hauv qhov sib piv, peb cov kab mob CPE KO nas nyob rau hauv Camk2apromotor tau pom tias tsis muaj kev nco thiab neurodegeneration, txhawb qhov kev xav tias CPE yog cov protein tiv thaiv neuro tiv thaiv kev ntxhov siab [36].
Kev tshawb fawb ntawm CPE-KO nas tau nthuav tawm ntau theem ntawm qhov txawv txav. Kev coj cwj pwm, CPE-KO nas qhia kev nyuaj siab-zoo li tus cwj pwm thiab kev kawm tsis taus. Electrophysiological tsom xam pom tias lub sij hawm ntev potentiation ntawm hippocampus nyob rau hauv CPE-KO nas yog impaired. Morphological tsom xam pom tias lub hippocampus degenerated tom qab kev ntxhov siab thaum CPE raug knockedout [31]. CPE yog tswj hwm nyob rau hauv ntau hom kev ntxhov siab thiab tseem ceeb hauv kev tiv thaiv neurons [3]. Cov txiaj ntsig ntawm CPEprotein deficiency ntawm prefrontal cortex nyob rau hauv kev ntxhov siab tsis tau tshaj tawm.
Tsis muaj qhov tsis ntseeg tias tus cwj pwm ntawm kev kawm thiab kev nco yuav tsum muaj kev sib cuam tshuam ntawm lub hlwb loj. Nco thiab nco qab yog nyob ntawm kev sib cuam tshuam ntawm prefrontalcortex thiab hippocampus [37]. Yog li ntawd, hippocampal prefrontal cortex Circuit Court plays lub luag haujlwm tseem ceeb hauv kev paub txog kev tswj hwm thiab kev nco ua ke [38]. Hauv CPE-KO nas, kev tshem tawm ntawm CPE protein ua rau raug mob rau hippocampal CA3 neurons [39].
Cov kev tshawb fawb yav dhau los tau qhia tias qhov kev ntxhov siab tsis tu ncua txhawb nqa glucocorticoid secretion thiab ua rau muaj kev tawm tsam neuronal hauv DG granulosacells kom nce glutamate secretion, ua rau excitotoxicity thiab tuag ntawm CA3 neurons hauv CPE-KO nas [40]. Tej zaum nws yuav yog tias cKOof CPE noob hauv cov neurons muaj qhov cuam tshuam tsawg dua ntawm cov kab mob endocrine.
Nws kuj tau pom tias tom qab lub sijhawm hloov pauv thoob ntiaj teb, neurons hauv thaj av CA1 tau muaj kev cuam tshuam ntau dua thiab tsuas yog pom qhov nce ntxiv hauv CPE qhia [41]. Geneticlesions ntawm hippocampal Sub-regions tau qhia qhov txawv ntawm kev kawm thiab kev nco [42]. Lub voj voog "trisynaptic" classic (DG > CA3 > CA1 > Sub) yog ib qho kev txiav txim siab thiab ib nrab ntawm cov dorsal-rau-dorsal, nruab nrab, nruab nrab mus rau nruab nrab, thiab ventral-to-ventral projection [43].
Lub hauv paus tseem ceeb ntawm kev tsim cov tsiaj txhu hippocampal yog ib lub voj voog unidirectional, uas cov ntaub ntawv xa tawm los ntawm cov txheej txheem ntawm lub cev nkag mus rau DG tau ua tiav hauv CA subfield: CA3, CA2, thiab CA1. Dorsal CA1 xa nws cov ntsiab lus ncaj qha mus rau sab hauv lub cev cortex txheej 5 los yog indirectly dhau ntawm dorsal Sub (ib qho kev taw qhia) [42].
Ib qho ntawm qhov sib txawv ntawm qhov ncaj thiab tsis ncaj hippocampal outputpathways yog qhov tom kawg, dorsal Subprojects rau entorhinalcortex txheej 5 thiab ntau thaj tsam cortical thiab subcortical hlwb [44]. Qee qhov kev tshawb fawb soj ntsuam tau pom tias DG thiab CA subfields tau xaiv ua haujlwm thaum lub sijhawm tsim lub cim xeeb, thaum Sub tseem ua haujlwm thaum lub sijhawm rov nco txog ib ntu [45].
Hauv qhov kev tshawb fawb no, kev qhia ntawm CPE protein nyob rau hauv hippocampus thiab dmPFC ntawm CPEflox / flox nas poob qis heev. Yog li ntawd, neural raug mob thiab apoptosis nyob rau hauv subregion ua rau nco tsis txaus. Hauv CPEflox / flox nas, neurological deficits tej zaum yuav yog vim ib feem ntawm cov nyiaj them poob haujlwm, nrog rau kev raug mob rau hippocampalSub thiab dmPFC neurons.
Astrocytes kho qhov kev loj hlob, lub cev, thiab cov txheej txheem pathological [46]. Lawv raug suav hais tias yog qhov tseem ceeb ntawm kev txhawb nqa ntawm neuron muaj nuj nqi, muab cov txheej txheem thiab metabolic txhawb rau cov neurons [47]. Astrocytes cuam tshuam rau kev nrhiav neeg ua haujlwm thiab kev ua haujlwm ntawm cov neurons hauv zos thiab hauv network [48]. Peb pom tias tus naj npawb ntawm astrocytic hlwb nyob rau hauv hippocampal Sub thiab dmPFC qhov tseem ceeb txo qis, tej zaum vim CPE yog ib qho tseem ceeb nyob rau hauv lub differentiation ntawm neural qia hlwb rau astrocytes [49].
BDNF suav hais tias yog ib qho tseem ceeb ntawm kev tswj hwm ntawm ntau yam kev ntxhov siab [50] .Nws tswj kev sib kis ntawm synaptic thiab lub sijhawm ntev potentiation hauv hippocampus thiab koom nrog kev tsim ntawm qee yam kev nco [51]. Tsis ntev los no, CPE tau qhia tias yog qhov tseem ceeb ntawm kev loj hlob thiab trophic yam tseem ceeb tiv thaiv hippocampus tiv thaiv kev ntxhov siab vim yog pyramidal neuron tuag thiab kev paub tsis meej [36]. Hauv txoj kev tshawb no, peb pom tias qhov kev qhia ntawm BDNF yog qhov sib npaug ntawm WT nas. Cov txiaj ntsig no qhia tau hais tias txawm hais tias qhov kev nthuav qhia zoo sib xws ntawm BDNF, CPEflox / flox nas nthuav tawm ua tiav neurodegeneration nrog kev ntxhov siab hnyav.
TEEB MEEM
Hauv cov ntsiab lus, txoj kev tshawb no qhia tau hais tias CPEflox / flox nas muaj kev cuam tshuam kev kawm thiab kev nco qab nyob rau hauv kev ntxhov siab ntawm kev xav thiab lub cev kev ntxhov siab cuam tshuam nrog kev txiav.
Qhov txo qis CPEexpression thiab kev ntxhov siab ua rau hippocampal Sub-degeneration, txo qis neurogenesis hauv DG, thiab txo qis neuronal ntom hauv hippocampal Sub thiab dmPFC.
REFERENCES
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