Ionizing Radiation-Induced Brain Cell Aging And The Potential Underlying Molecular Mechanisms Part 1

Abstract:

Cov neeg laus laus tau tshwm sim sai heev thoob ntiaj teb, nyuaj rau kev lag luam thoob ntiaj teb thiab kev pabcuam kev noj qab haus huv. Kev laus ntawm lub hlwb yog ib qho tseem ceeb rau ntau lub hnub nyoog ntsig txog kev mob hlwb thiab neuropsychological, nrog rau Alzheimer's disease thiab Parkinson's disease.

Raws li kev laus ntawm cov pejxeem nce, tib neeg tau them nyiaj ntau dua rau kev sib raug zoo ntawm lub hlwb laus thiab kev nco. Raws li kev tshawb fawb, tib neeg lub hlwb yuav maj mam poob qee qhov haujlwm thaum muaj hnub nyoog, tshwj xeeb tshaj yog nco. Yog li dab tsi yog kev sib raug zoo ntawm lub hlwb laus thiab kev nco?

Ua ntej tshaj plaws, kev laus lub hlwb tsis yog ib qho teeb meem uas txhua tus neeg ntsib. Peb tuaj yeem ncua kev laus ntawm lub hlwb los ntawm kev noj qab haus huv. Nws yog kev tshawb fawb pov thawj tias kev tawm dag zog, tswj kev noj zaub mov zoo, thiab koom nrog kev cob qhia kev paub tsis tu ncua tuaj yeem muaj kev cuam tshuam zoo rau lub hlwb kev noj qab haus huv thiab txhawb kev loj hlob thiab kev sib txuas ntawm neurons.

Ntxiv rau, peb kuj tuaj yeem sim qee txoj hauv kev los txhim kho kev nco. Piv txwv li, peb tuaj yeem ntxiv dag zog rau kev nco los ntawm kev tshuaj xyuas ntau zaus, siv kev sib koom ua ke, thiab tsim kom muaj kev nkag siab ntawm cov lus. Cov hau kev no tuaj yeem pab peb qhib qhov chaw nco txog xws li hippocampus thiab amygdala hauv lub hlwb, thiab txhim kho peb lub cim xeeb.

Tsis tas li ntawd, peb kuj tuaj yeem ua kom tsim nyog siv cov cuab yeej siv rau kev cob qhia nco. Ntau yam kev ua si nco, apps, thiab cov cuab yeej tuaj yeem pab peb txhim kho kev nco thiab kev xav, xws li Flipd, BrainHQ, Elevate, thiab lwm yam. Cov apps thiab cov cuab yeej siv cov kev tshawb fawb txog kev txawj ntse tshiab los tsim cov kev qhia kev nco tus kheej raws li peb xav tau thiab nyiam.

Tag nrho hauv tag nrho, qhov cuam tshuam ntawm kev laus lub hlwb ntawm kev nco tsis tas yuav ua rau peb ntshai. Tsuav peb ua raws li txoj kev noj qab haus huv, tsom mus rau kev txawj ntse, thiab sim ntau txoj hauv kev los txhim kho kev nco, peb tuaj yeem ncua kev laus ntawm lub hlwb, txhim kho peb lub cim xeeb thiab kev xav, thiab muaj kev noj qab haus huv thiab ua tiav lub neej. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.

Nyem paub 10 txoj hauv kev los txhim kho kev nco

Ntau yam extrinsic yam, xws li raug rau ionizing hluav taws xob, tuaj yeem ua kom lub cev muaj zog. Ntau qhov kev tshawb fawb ntawm tib neeg thiab tsiaj txhu tau tshaj tawm tias raug ionizing hluav taws xob tuaj yeem muaj ntau yam cuam tshuam rau kev laus ntawm lub cev thiab ua rau lub neej ntev los yog luv luv nyob ntawm seb cov tshuaj tua hluav taws xob lossis cov koob tshuaj.

Daim ntawv no tshuaj xyuas cov teebmeem ntawm hluav taws xob rau kev laus ntawm ntau hom hlwb hlwb, suav nrog cov neurons, microglia, astrocytes, thiab cerebral endothelial hlwb. Tsis tas li ntawd, cov txheej txheem molecular tseem tau tham. Zuag qhia tag nrho, qhov kev tshuaj xyuas no qhia txog yuav ua li cas hluav taws xob-inducedsenescence nyob rau hauv ntau hom ntawm tes yuav ua rau lub hlwb laus, uas yuav ua rau muaj kev loj hlob ntawm ntau yam neurological thiab neuropsychological mob.

Yog li ntawd, kev kho mob tsom rau hluav taws xob-induced oxidative kev nyuaj siab thiab neuroinflammation yuav tiv thaiv tau hluav taws xob-induced hlwb laus thiab theneurological thiab neuropsychological teeb meem nws yuav ua tau.

Ntsiab lus: ionizing hluav taws xob; kev laus; hlwb; oxidative kev nyuaj siab; mitochondrial tsis ua haujlwm; DNA puas.

1. Taw qhia

Cov neeg laus laus hauv ntiaj teb tam sim no tshwm sim ntawm tus nqi uas tsis tau pom dua. Tau muaj kev hloov pauv pej xeem mus rau cov neeg laus, thiab qhov no yuav muaj qhov tshwm sim deb heev. Cov neeg laus laus yog suav tias yog kev kub ntxhov los ntawm kev lag luam thoob ntiaj teb thiab kev saib xyuas kev noj qab haus huv [1].

Nyob rau hauv feem ntau hom, lub geriatric theem ntawm lub neej cuam tshuam rau kev puas tsuaj ntawm adaptation thiab tus kheej-ntsuas mechanisms, uas ua rau kom muaj zog susceptibility rau ib puag ncig los yog sab hauv siab, kab mob, thiab kev tuag [2].

Hauv tib neeg, kev laus yog txuam nrog kev paub txog kev paub thiab lub cev tsis zoo, nrog rau kev pheej hmoo ntawm cov kab mob xws li kab mob neurodegenerative. Lub hnub nyoog cuam tshuam txog kev tsis taus thiab kev mob tsis zoo cuam tshuam rau tib neeg lub neej zoo, thaum kawg ua rau muaj kev pheej hmoo ntawm kev tuag, thiab ua rau muaj teeb meem ntawm tus kheej, tsev neeg, thiab zej zog [3].

Kev laus ntawm lub hlwb, uas cuam tshuam nrog cov cellular thiab molecular mechanisms uas thaum kawg ua rau kev paub tsis meej, yog qhov tseem ceeb rau neurodegeneration [4].

Kev laus ua rau muaj kev puas tsuaj zuj zus hauv lub hlwb lub peev xwm ua haujlwm, uas ua rau muaj kev cuam tshuam kev kawm thiab kev nco, kev saib xyuas tsis txaus, txo kev txiav txim siab ceev, thiab tsis pom kev thiab lub cev muaj zog [5].

Lub hnub nyoog cuam tshuam txog kev ua haujlwm ntawm lub hlwb tshwm sim yuav luag sib npaug rau kev ua haujlwm tsis zoo ntawm lwm cov kabmob hauv nruab nrog cev, thiab kev poob qis hauv kev ua haujlwm tau nrawm nrawm tom qab hnub nyoog 50 xyoo [6].

Txawm li cas los xij, kev hloov pauv ntawm kev laus ntawm cov cellular kev ncaj ncees thiab txoj hauv kev molecular tau sib koom ua ke, suav nrog lub hlwb [7]. Cov kev hloov pauv no suav nrog kev ua haujlwm mitochondrial; intracellular tsub zuj zuj ntawm oxidative kev puas tsuaj rau macromolecules; dysregulation ntawm lub zog metabolism; kev puas tsuaj ntawm cov khoom pov tseg ntawm tes (autophagy-lysosome thiab proteasomefunctions), kev hloov pauv kev ntxhov siab, thiab kho DNA; thiab mob. Tsis tas li ntawd, kev ua haujlwm ntawm lub paj hlwb tsis zoo, hloov pauv Ca2+ ua haujlwm hauv cov neurons, thiab txo qis neurogenesis kuj tau pom hauv lub hlwb laus [8,9].

Tag nrho cov kab mob uas muaj sia nyob tau dhau kev laus thiab raug ionizing hluav taws xob (IR) thoob plaws hauv lawv lub neej. Ntau qhov kev tshawb fawb tau txuas IR kom nrawm nrawm [10]. Kuzmic et al.used glp-1 sterile Caenorhabditis elegans los ntsuas qhov cuam tshuam ntawm gamma hluav taws xob ntev ntawm lub neej thiab paub tseeb tias IR tuaj yeem ua rau kev laus [11]. Kev raug rau IR paub tias ua rau muaj ntau yam kev hloov pauv ntawm lub cev.

IR tuaj yeem ua rau DNA ob-strandbreaks (DSBs), uas ua rau cov caj ces tsis ruaj khov DNA puas thiab oxidative kev nyuaj siab, ua rau lub hlwb endothelial cell senescence thiab cell tuag [12,13]. Cellular senescence, anirreversible lub xeev ntawm kev loj hlob stagnation, tuaj yeem pab peb nkag siab qhov cuam tshuam ntawm kev laus rau ob peb lwm yam kev lom neeg, los ntawm kev loj hlob ntawm embryonic mus rau cov ntaub so ntswg kho thiab cov kab mob ntsig txog kev laus [14,15].

Kev siv tshuaj ntau dhau tuaj yeem ua rau mob hluav taws xob mob hnyav, thaum lub sijhawm ntev ntawm cov hluav taws xob tsawg feem ntau ua rau muaj mob ntev xws li kab mob neurodegenerative. Txawm hais tias muaj kev phom sij ntawm cov koob tshuaj ntau / koob tshuaj IR ntawm tib neeg kev noj qab haus huv tau tsim muaj txiaj ntsig zoo, cov txiaj ntsig ntawm kev siv tshuaj tsawg / koob tshuaj feem ntau raug saib xyuas txawm tias nws qhov xwm txheej.

Kev siv IR hauv kev kuaj mob thiab kev kho mob qog noj ntshav tau nce ntxiv. Yog li ntawd, nuclear pov tseg los ntawm cov tsev kho mob suav txog kwv yees li 14% ntawm lub ntiaj teb tag nrho cov hluav taws xob txhua xyoo [16].

Ntau qhov kev tshawb fawb tau pom tias qhov ntev ntev ntawm cov tshuaj IR tsawg hauv cov chaw kuaj catheterization ua rau muaj kev pheej hmoo ntawm cov kab mob plawv, qhia tias nws ua rau txhim kho vascularaging thiab ntxov atherosclerosis [17].

Ntau tshaj 50% ntawm cov neeg mob qog noj ntshav yuav tau kho nrog radiotherapy. Kev kho hluav taws xob yuav tua cov qog nqaij hlav thaum tseem ua rau cov ntaub so ntswg nyob ib puag ncig, ua rau hluav taws xob toxicity. [18]. Radiotherapy nthuav tawm ob lub qog nqaij hlav thiab ib puag ncig IR noj qab haus huv, ua rau DNA puas tsuaj, uas ua rau DNA puas tau teb (DDR). Hauv cov tshuaj tiv thaiv no, ionizing hluav taws xob yuav ua rau lub voj voog ntawm tes nres thiab ua rau cov cell puas, thiab cov hlwb puas yuav kho tau. Yog tias DNAis kho tag nrho, cov hlwb no tuaj yeem rov zoo li qub.

Txawm li cas los xij, thaum cov xwm txheej sab hauv thiab sab nraud cuam tshuam rau lub peev xwm ntawm kev kho DNA, kev laus (xws li, lub voj voog ntawm tes raug ntes) lossis celldeath (xws li apoptosis lossis mitotic kev puas tsuaj) yuav tshwm sim. [19,20]. Tsis tas li ntawd, raws li IR feem ntau xav tau kom tau txais cov duab daws teeb meem siab thaum lub sij hawm neuroimaging, qhov kev koom tes ntawm cov koob tshuaj qis / koob tshuaj IR rau cov kab mob neurodegenerative yuav tsum tau kuaj xyuas [21].

Kev raug hluav taws xob, tshwj xeeb tshaj yog cov hluav taws xob raug hluav taws xob, tshwm sim hauv tib neeg niaj hnub. Qee cov khoom siv hluav taws xob hauv lub ntiaj teb xws li uranium (238U), poov tshuaj (40K), thorium (232T), thiab lawv cov khoom siv hluav taws xob, xws li radon (222Rn) thiab radium (226Ra) ua raws li ntuj tsim hluav taws xob raug [22] ].

Cov cheeb tsam uas muaj qib siab ntawm cov hluav taws xob tom qab tau suav tias yog qhov zoo tshaj plaws rau kev tshawb xyuas qhov cuam tshuam mus ntev ntawm cov hluav taws xob qis qis hauv tib neeg [23]. Qee qhov kev tshawb fawb txog hluav taws xob zoo nkauj tau ua hauv Brazil, Tuam Tshoj, Is Nrias teb, thiab Iran [24-26]. Kev siv hluav taws xob ntau ntau tuaj yeem ua rau mob qog noj ntshav.

Tsis tas li ntawd, nws tsim nyog sau cia tias cov hluav taws xob zoo li qub tau pom hauv Yangjiang, Tuam Tshoj kuj tseem ua rau muaj qee yam kab mob uas tsis yog mob qog noj ntshav, xws li tuberculosis, kab mob plab, thiab kab mob cerebrovascular. [27]. Lub ntuj tsim hluav taws xob siab nyob rau hauv ib puag ncig tuaj yeem suav tias yog hom kev ua qias tuaj. Nws tuaj yeem ncav cuag tib neeg lub cev los ntawm ob qho tib si sab hauv thiab sab nraud, thiab tuaj yeem ua rau tib neeg DNA puas.

Tsis tas li ntawd, cov hluav taws xob tom qab ntuj kuj nkag mus rau hauv ecosystem los ntawm tib neeg kev ua ub no, cuam tshuam rau kev noj qab haus huv thiab lub neej zoo ntawm cov tib neeg nyob hauv cov cheeb tsam uas muaj hluav taws xob zoo li qub. array ntawm cov kab mob nyob rau hauv cov neeg raug kis thoob plaws tag nrho cov contaminatedregions soj ntsuam.

Tshwj xeeb, kev hloov pauv rau lub hauv nruab nrab lub paj hlwb (CNS), uas ua rau muaj kev cuam tshuam ntawm cov hlab ntsha hauv lub paj hlwb, tau pom nyob rau hauv ntau tus neeg [28].Ntxiv mus, muaj sia nyob Chornobyl liquidators pom cov tsos mob ntawm qhov mob uas tuaj yeem cuam tshuam nrog kev laus ntxov ntxov [29]. Radiation-induced immune system impairments yog ib qho tseem ceeb contributors rau physiological hloov uas tshwm sim sai tom qab hluav taws xob exposure thiab tau cuam tshuam nyob rau hauv ncua kev cuam tshuam ntawm hluav taws xob xws li qog loj hlob thiab thaum ntxov laus [30].

Kev siv tshuaj tsawg tsawg IR raug tuaj yeem ua rau cov hlab ntsha laus, suav nrog cov hlab ntsha hlwb. Qhov no tau pom tias muaj feem cuam tshuam nrog cov hnub nyoog ntsig txog kev mob ntshav qab zib hauv cov neeg muaj hnub nyoog tshaj 40 xyoo, nrog rau cov kab mob atherosclerosis [31,32].

Ntawm 306 tus neeg ua haujlwm raug chornobyl nuclear kev sib tsoo tshuaj xyuas qhov kev tshawb fawb dhau los, 81% thiab 77% ntawm cov txiv neej thiab poj niam, raws li, pom cov cim ntawm kev laus zuj zus.

Tsis tas li ntawd, cov hnub nyoog qis dua 45 xyoo tau pom tias muaj kev cuam tshuam ntau dua rau cov hluav taws xob vim qhov ua kom muaj kev laus [33]. Nyob rau hauv tib neeg, rhiab heev rau hluav taws xob txo qis nrog lub hnub nyoog mus txog rau thaum ib tug neeg laus. Txawm li cas los xij, qhov kev xav no ua rau muaj hnub nyoog laus zuj zus.

Kev sim cov ntaub ntawv los ntawm cov tsiaj kuj txhawb txoj kev xav tias IR induces aging.Brizzee tau pom tias nrog lub hnub nyoog nce, qee qhov kev hloov pauv tshwm sim hauv cerebral cortices ntawm Rhesus liab thiab albino nas [34].

Kev soj ntsuam ntawm transcriptomic profiles los ntawm murinebrains qhia tau hais tias cov lus teb molecular pom cov sij hawm tom qab tag nrho lub cev qis-doseirradiation (100 mGy) zoo ib yam li cov uas cuam tshuam nrog kev paub ntxov ntxov ntxov, Alzheimer's kab mob, thiab ntau yam neuropsychiatric mob [35,36]. Cov transcriptomicprofiles ntawm microglia tau txais ib hnub thiab ib lub hlis tom qab irradiation kuj zoo ib yam li cov neeg pom thaum lub sij hawm laus, taw qhia rau cov laus-txhim kho cov teebmeem ntawm hluav taws xob [37].

Nyob rau hauv vitro high-dose (2-8 Gy) irradiation ntawm thawj cerebrovascular endothelial hlwb nyob rau hauv naspromotes ib tug secretory phenotype txuam nrog kev laus, tus cwj pwm los ntawm lub upregulation ntawm pro-inflammatory cytokines thiab chemokines, xws li IL-6, IL{{5} } , and MCP-1 [38].

Nws tau raug tshaj tawm tias IR nce cellular senescence, thiab senescence-associated -galactosidase (SA- -Gal) thiab senescence-specific genes (p16, p12, thiab Bcl-2) tau nthuav tawm hauv cov pob txha pob txha irradiated- Yuav ua li cas los tsim macrophages [39] Cov kev tshawb pom no corroboratethe nyob rau hauv vivo pov thawj taw qhia rau lub peev xwm senescence-inducing cuam tshuam ntawm hluav taws xob nyob rau hauv endothelial hlwb ntawm cerebral hlab ntsha.

Ua ke, nws yog qhov tseeb tias cov teebmeem lom ntawm IR raug, tsis txwv rau oxidativestress, chromosomal puas, apoptosis, qia cell tsis ua hauj lwm, thiab o, tag nrho cov contributeto accelerate aging [40]. Tsis tas li ntawd, qhov kev koom tes ntawm IR raug rau kev txhim kho cov mob tsis zoo xws li cov kab mob neurodegenerative kuj tau tshwm sim los ntawm kev tshawb fawb txog kab mob sib kis [21], thiab ntau yam kev kho mob muaj feem cuam tshuam rau ntau hom kev siv hluav taws xob tsawg / koob tshuaj (Table 1) .

Hauv kev tshuaj xyuas no, peb yuav tsom mus rau qhov cuam tshuam ntawm IR ntawm lub hlwb kev laus, suav nrog kev laus ntawm ntau hom CNS cell (microglia, astrocytes, cerebral endothelial hlwb, thiab neurons). Tsis tas li ntawd, cov txheej txheem molecular cuam tshuam yuav raug sib tham, thiab cov kev tshawb fawb yav tom ntej tau hais los ntawm kev nthuav qhia qhov tseeb cuam tshuam ntawm hluav taws xob ua rau lub hlwb laus yuav raug npaj.

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