Zebrafish, Medaka Thiab Turquoise Killifish Kom Nkag Siab Tib Neeg Neurodegenerative/Neurodevelopmental Disorders Part 5
Mar 28, 2024
5. Tib neeg Neurodevelopmental Disorders nyob rau hauv Me Fishes
Tib neeg cov kab mob neurodevelopmental raug kuaj pom raws li kev txheeb ze ntawm tus neeg tus cwj pwm thiab tib neeg, xws li kev loj hlob thiab kev nyuaj hauv lub neej, tsis yog raws li kev kuaj mob caj ces lossis biomarkers xws li MRI scans [123].
Neurodevelopmental disorders hais txog qee yam teeb meem lossis teeb meem hauv kev txhim kho lub paj hlwb thaum yau, uas cuam tshuam rau tus menyuam lub cev, kev txawj ntse, thiab kev loj hlob ntawm tus cwj pwm. Tus kab mob no tshwm sim hauv cov menyuam yaus thiab ntau tus menyuam raug cuam tshuam. Txawm li cas los xij, cov kab mob neurodevelopmental tsis txhais hais tias cov menyuam yaus yuav raug cuam tshuam rau lawv lub neej. Nrog rau kev cuam tshuam txog kev tshawb fawb thiab kev saib xyuas tsev neeg, cov menyuam yaus tuaj yeem loj hlob thiab muaj kev noj qab haus huv rau cov neeg laus.
Kev nco yog ib qho tseem ceeb ntawm kev txawj ntse ntawm tib neeg. Nws yog ib feem tseem ceeb ntawm peb lub neej niaj hnub thiab kev kawm ua haujlwm. Qhov cuam tshuam ntawm neurodevelopmental disorders ntawm lub cim xeeb yog tshwm sim nyob rau hauv cov nram qab no yam: Ua ntej, neurodevelopmental disorders tej zaum yuav cuam tshuam rau cov me nyuam txoj kev muaj peev xwm kawm tau ntawv. Vim tias txoj kev loj hlob ntawm lub paj hlwb raug cuam tshuam, tus me nyuam yuav muaj teeb meem ntawm kev hais lus thiab kev sib txuas lus, uas tuaj yeem ua rau nws nyuaj rau tus menyuam kom nkag siab txog kev paub thiab cov ntaub ntawv kawm uas tus xibfwb qhia. Tib lub sijhawm, cov menyuam yaus yuav tsis muaj kev xav thaum lub sijhawm kawm thiab muaj kev nyuaj siab rau kev ua tiav cov haujlwm, uas yuav cuam tshuam rau lawv lub cim xeeb.
Qhov thib ob, cov kab mob neurodevelopmental tuaj yeem cuam tshuam rau tus menyuam lub peev xwm los sib tham thiab tswj kev xav. Qhov no tuaj yeem ua rau menyuam yaus nyuaj rau kev sib tham nrog cov phooj ywg thiab tsim kev sib raug zoo nrog lawv. Qhov teeb meem kev noj qab haus huv thiab kev xav no tuaj yeem ua rau tus menyuam lub hlwb tsis ruaj khov, uas tuaj yeem cuam tshuam kev nco.
Txawm li cas los xij, txawm hais tias neurodevelopmental disorders muaj qee yam cuam tshuam rau kev nco, qhov no tsis tau txhais hais tias cov me nyuam tsis tuaj yeem muaj peev xwm nco tau zoo. Nrog rau kev cuam tshuam txog kev tshawb fawb thiab kev saib xyuas tsev neeg, cov menyuam yaus tuaj yeem maj mam kov yeej cov teeb meem no. Cov niam txiv tuaj yeem pab lawv cov menyuam tsim kev kawm zoo raws li lawv cov kev xav tau, muab cov kev qhia tshwj xeeb, thiab ua haujlwm nrog cov kws qhia ntawv los koom ua ib qho chaw zoo rau lawv cov menyuam txoj kev loj hlob thiab kev loj hlob.
Tsis tas li ntawd, cov menyuam yaus uas koom nrog qee yam kev ua kis las, kev ua suab paj nruag, thiab lwm yam uas tsim nyog rau lawv kuj tuaj yeem muaj txiaj ntsig zoo rau lawv txoj kev loj hlob ntawm lub cev thiab kev txawj ntse. Nws tseem tuaj yeem pab ntxiv dag zog rau lawv lub peev xwm kev sib raug zoo thiab kev xav, yog li txhim kho lawv lub cim xeeb.
Nyob rau hauv luv luv, neurodevelopmental disorders tej zaum yuav muaj tej yam cuam tshuam rau cov me nyuam txoj kev nco, tab sis qhov no tsis cuam tshuam rau tus me nyuam txoj kev loj hlob noj qab haus huv. Los ntawm kev cuam tshuam txog kev tshawb fawb thiab kev saib xyuas tsev neeg, cov menyuam yaus tuaj yeem maj mam kov yeej cov teeb meem, txhim kho kev nco zoo, thiab loj hlob mus rau cov txuj ci tseem ceeb. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab 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, Cistanche deserticola kuj tseem 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 ntxiv los txhim kho kev nco
Ib qho kev txwv ntawm kev siv cov ntses me los kawm txog cov kab mob neurodevelopmental yog qhov tsis zoo uas cov ntses me me yuav ua tau raws li kev kuaj mob rau cov tib neeg cov kab mob neurodevelopmental.
Txawm hais tias nws yog qhov nyuaj rau kev siv cov kev ua haujlwm siab dua ntawm tib neeg rau zebrafish, muaj cov lus ceeb toom nyob rau xyoo tas los no tias zebrafish tuaj yeem siv tau asa qauv tsiaj rau cov kab mob neurodevelopmental los ntawm kev siv cov kev ntsuam xyuas tus cwj pwm uas ua rau tib neeg cov lus teb.
Tsis tas li ntawd, raws li twb tau hais lawm, qhov kev siv ntawm cov ntses me me hauv chav kuaj ua tus qauv tsiaj rau cov kab mob neurodevelopmental tau ua rau ntau qhov kev tshawb pom zoo nyob rau hauv cov nqe lus ntawm kev soj ntsuam zoo ib yam los ntawm cov cellular thiab molecular nplai rau cov nqaij mos, kev loj hlob, thiab kev coj cwj pwm tsom xam.Autism spectrum disorder ( ASD) yog ib qho ntawm feem ntau cov kab mob neurodevelopmentaldisorders.
Txawm hais tias qhov pathogenesis ntawm ASD tseem tsis tau tsim, kev tshawb pom los ntawm kev txheeb xyuas cov noob caj noob ces ntawm cov neeg mob ASD tau sau tseg, thiab adatabase ntawm cov noob caj noob ces rau qhov pib ntawm ASD tau raug tsim. SFARI (https://gene.sfari.org/; nkag mus rau 30 Kaum Ib Hlis 2021), cov ntaub ntawv ua haujlwm los ntawm Simon Foundation hauv Tebchaws Meskas, muaj rau siv. Tam sim no muaj 1023 cov noob sau npe tau muab cais los ntawm kev siv zog.
Tsis tas li ntawd, cov yam ntxwv ntawm caj ces tau raug lees paub nyob rau hauv cov kab mob ntawm kev tsis txaus ntseeg / kev tsis txaus ntseeg siab (ADHD), thiab nyob rau xyoo tas los no, kev tshawb pom los ntawm kev tshuaj ntsuam xyuas meta-tshuaj ntsuam xyuas ntawm genome-wide koom haum soj ntsuam tau sau [124-126]. Cov nram qab no yog cov ntsiab lus ntawm kev tshawb fawb qhia siv zebrafish mutant qauv ntawm cov noob xav tias yuav koom nrog cov kab mob neurodevelopmental (Table 2).
DYRK1A yog ib qho serine / threonine kinase uas yog ib qho tseem ceeb rau lub hlwb kev loj hlob thiab kev ua haujlwm, thiab overactivation ntawm cov protein no tau pom hauv Down syndrome [133]. Tsis tas li ntawd, DYRK1A belongs rau cov qhab nia 1 hauv SFARI database thiab suav tias yog cov noob caj noob ces muaj feem cuam tshuam rau ASD. Kim et al. tsim thiab tshuaj xyuas Dyrk1aa knockoutzebrafish, ib qho orthologue ntawm DYRK1A.
Lawv tau pom tias tus neeg laus knockout ntses pom microcephaly, kev soj ntsuam tus cwj pwm tau pom tias tus cwj pwm kev ntxhov siab tau txo qis los ntawm qhov kev ntsuam xyuas tshiab, thiab kev sib raug zoo ntawm kev sib raug zoo raug cuam tshuam los ntawm kev sim shoaling thiab kev nyiam ntawm kev sib raug zoo.
Lawv xaus lus tias qhov no yog kev hloov pauv tus cwj pwm zoo li autistic hauv ntses [127]. Ib yam li ntawd, zebrafish orthologue knockout kab tau tsim rau SHANK3 thiab NRXN2, uas yog tus qhab nia 1 ntawm ASD cov noob caj noob ces hauv SFARI database. SHANK3 tau qhia thoob plaws hauv lub hlwb thiab feem ntau koom nrog hauv kev tsim cov postsynapticscaffolds thiab neurotransmission [134].
Liu et al. tsim Shank3b knockout zebrafish uas pom tias muaj kev cuam tshuam kev sib raug zoo los ntawm kev txheeb xyuas tus cwj pwm thiab qhia txog kev txo qis ntawm Homer1, SHANK-binding protein, hauv cov neeg laus ntses hlwb [128]. NRXN2 yog ib qho transmembrane protein uas nyob rau hauv lub presynaptic davhlau ya nyob twg thiab koom nrog insynapse tsim thiab neurotransmitter tso tawm mechanisms [135].
NRXN2 knockoutmice tau siv los ua tus qauv rau kev puas hlwb thiab tau pom tias muaj kev ntxhov siab zoo li tus cwj pwm hauv kev ntsuam xyuas xws li lub teeb / tsaus lub thawv kuaj thiab qhov siab ntxiv rau mazetest [136]. Koh et al. generated Nrxn2a knockout zebrafish thiab pom muaj kev ntxhov siab-zoo li tus cwj pwm hauv qhov kev sim tshiab tank, qhia tias kev hloov pauv tus cwj pwm zoo li autism kuj tshwm sim hauv zebrafish [129].
PER1 yog lub npe hu ua lub moos gene, thiab genome-wide koom haum tsom xam ntawm ADHD cov neeg mob qhia tias cov noob no yog cov noob caj noob ces rau ADHD [124]. Huang et al. tsim Per1bknockout zebrafish thiab pom tias cov menyuam yaus muaj lub siab ua haujlwm siab, tau nce kev tawm tsam ntau zaus hauv daim iav-duab kev sim tua, thiab tau txais kev cawmdim los ntawm microinjection ntawm per1b mRNA.
Lawv kuj tau pom tias cov ntsiab lus dopamine tau txo qis hauv Per1b knockout zebrafishbrains thiab tias cov phenotype overactive tuaj yeem cawm tau los ntawm selegiline (monoamineoxidase B inhibitor) lossis methylphenidate (dopamine transporter inhibitor, human ADHDtreatment).
Lawv kuj tau txheeb xyuas PER1 cov nas nas. Zoo ib yam li cov qauv zebrafish, PER1knockout nas tau pom qhov ua siab loj thiab txo cov ntsiab lus dopamine hauv cov qauv hauv hlwb, qhia txog qhov muaj peev xwm PER1 qhov txawv txav tuaj yeem koom nrog hauv dopaminergic neuralabnormalities hauv ADHD [131]. Daim ntawv tshaj tawm no yog qhov zoo heev vim tias nws tau qhia txog kev txuag phenotype ntawm cov kab mob vertebrate, nrog rau cov cwj pwm coj cwj pwm.
Txhawm rau txiav txim siab li cas tus cwj pwm coj tus cwj pwm ntawm zebrafish qhia cov tsos mob ntawm tib neeg cov kab mob neurodevelopmental, "reactivity to anxiety" sib raug rau sensoryhypersensitivity / sensory deprivation nyob rau hauv autism spectrum disorders, "tsis muaj neeg coob coob" raws li nyuaj hauv kev sib txuas lus thiab interpersonal interactions thiab "hyperactivity" phenotypes rau hyperactivity / impulsivity cov tsos mob hauv ADHD, tuaj yeem soj ntsuam hauv txhua qhov kev xeem.
Txawm hais tias qhov sib txawv ntawm anatomical thiab physiological tsis meej nyob rau hauv cov qauv kab mob, yog tias qee qhov phenotype tuaj yeem tau los ntawm kev txheeb xyuas tus cwj pwm, nws yuav raug siv los ua qhov tseem ceeb los ntsuas seb qee qhov kev cuam tshuam puas tuaj yeem muab kev cawm dim, xws li kev tshuaj ntsuam xyuas pharmacological high-throughput [130- 132] ib.
Dab tsi yuav tsum tau ua tib zoo xav yog nws txoj kev txhais lus hauv kev txheeb xyuas tus cwj pwm. Txawm hais tias kev txheeb xyuas tus cwj pwm ntawm miceh muaj keeb kwm ntev thiab tau ua qauv los ntawm ntau tus kws tshawb fawb, kev txheeb xyuas tus cwj pwm ntawm zebrafish tseem nyob hauv nws txoj kev loj hlob theem.
Piv txwv li, qhov tshiab lub tank sim taug qab tus cwj pwm ntawm zebrafish tom qab lawv tau raug xa mus rau lub tank tshiab thiab sib sau ua ke thiab txheeb xyuas cov txheej txheem ntau npaum li cas lawv tau siv nyob rau qhov twg dej qhov tob thiab deb npaum li cas lawv taug kev. Hauv qhov kev ntsuam xyuas no, zebrafish thawj zaug siv sij hawm nkaum hauv qab ntawm lub tank thiab tom qab ntawd lawv maj mam nthuav lawv cov kev ua ub no rau saum npoo.
Yog tias nws tau pom tias covzebrafish siv sijhawm tsawg dua hauv qab ntawm lub tank thiab tam sim ntawd pib txav mus ze rau saum npoo, nws yuav muaj lub ntsiab lus sib txawv nyob ntawm seb nws puas tau piav qhia tias "tsis muaj kev ntxhov siab yooj yim" lossis "hyperactivity thiab impulsiveness". Saib cov ntawv xa mus rau cov npe ntawm tus cwj pwm zebrafish [137], cov ntsiab lus ntawm kev txheeb xyuas tus cwj pwm thiab nws cov kev txwv, thiab sib piv nrog kev txheeb xyuas tus cwj pwm hauv nas [138–140].
Kev txheeb xyuas tus cwj pwm saib tus cwj pwm ntawm cov ntses, tab sis nws yog ib qho tsim nyog yuav tsum xav txog lawv thaum siv lawv rau tib neeg. Nws yuav ua kom ntseeg tau ntau dua yog tias cov qauv hauv phenotypes tuaj yeem raug soj ntsuam hauv ntau qhov kev ntsuam xyuas, tsis yog ua cov kev xav raws li qhov tshwm sim ntawm ib qho kev ntsuas tus cwj pwm.
Ntxiv nrog rau kev txheeb xyuas tus cwj pwm, lwm hom kev uas tuaj yeem ntsuas qhov kev ntxhov siab kuj tseem raug txiav txim siab; Piv txwv li, los ntawm kev ntsuam xyuas qib cortisol, uas yog ib qho ntawm cov tshuaj hormones kev nyuaj siab [141–143].
Tseem muaj ntau yam tsis paub txog kev siv ntses me me asa qauv rau tib neeg lub hlwb ua haujlwm siab dua thiab tib neeg neurodevelopmental disorders, thiab peb cia siab tias kev tshawb fawb ntxiv yuav raug sau.
Tsis tas li ntawd, zebrafish kuj tau siv rau hauv thaj chaw ntawm kev puas siab puas ntsws los tshuaj xyuas tus mob schizophrenia thiab kev nyuaj siab. Nws yog qhov nthuav heev kom pom cov phenotype ntawm zebrafish ua tus qauv tsiaj rau cov tsos mob puas hlwb [144,145]. Txawm hais tias cov teb sib txawv, zebrafish tau siv zoo ib yam li tau piav qhia hauv qhov kev tshuaj xyuas no. Yog xav paub ntxiv, xa mus rau lwm cov ntawv tshaj tawm zoo tshaj [139,146,147].
6. Cov lus xaus
Hauv qhov kev tshuaj xyuas no, peb tau tham txog cov yam ntxwv ntawm zebrafish, medaka, thiab turquoisekillifish hauv chav kuaj thiab kev tshuaj xyuas tiag tiag ntawm cov kab mob neurodegenerative thiab neurodevelopmental disorders siv cov ntses me no. Hauv kev tsom xam ntawm tib neeg cov kab mob neurological, cov ntses me me yog cov qauv tsiaj zoo heev thiab yuav raug tsim kho ntxiv rau yav tom ntej. Lub sijhawm no, peb yuav tsum muaj kev txo hwj chim rau cov tsiaj txhu tsiaj txhu. Txawm hais tias muaj ntau yam kev sim tau pom hauv cov ntses me, yog tias tib yam tuaj yeem pom hauv nas, qhov cuam tshuam tuaj yeem ua rau cov nas ntau dua.
Txhawm rau ua kom pom lub ntsiab lus thiab muaj txiaj ntsig ntawm kev siv cov ntses me me, cov qauv kev tshawb fawb yuav tsum tau ua kom zoo dua ntawm cov yam ntxwv ntawm cov ntses me me thiab lawv cov txiaj ntsig hauv chav kuaj, raws li tau piav qhia hauv qhov kev tshuaj xyuas no. Tsis tas li ntawd, peb yuav tsum tsis txhob hnov qab tias peb tab tom saib tib neeg lub siab. system ntawm me ntses. Tej zaum nws yuav tsis paub meej tias qhov kev hloov pauv hauv RNA thiab cov proteins hauv cov ntses me me hauv cov ntsiab lus ntawm tib neeg cov kab mob thiab kev puas tsuaj txhais tau li cas yog tias peb tsuas yog saib xyuas cov ntses me xwb.
Tib yam siv rau lub ntsiab lus ntawm kev hloov pauv hauv morphology thiab kev ua haujlwm ntawm lub cev ntawm lub cev thiab lub ntsiab lus ntawm kev hloov pauv ntawm tus cwj pwm tau los ntawm kev txheeb xyuas tus cwj pwm. Lub ntsiab lus ntawm cov txiaj ntsig tau los ntawm cov ntses me me yuav ua kom pom tseeb thaum cov txiaj ntsig tau txuas rau cov tsiaj txhu tsiaj xws li nas thiab tom qab ntawd rau tib neeg kev soj ntsuam. Yog tias qhov kev sib raug zoo no tuaj yeem tsim los ntawm cov ntses me thiab lwm cov qauv, cov ntses no tuaj yeem dhau los ua cov cuab yeej muaj zog thiab muaj txiaj ntsig zoo rau kev daws teeb meem ntawm tib neeg lub paj hlwb.
Sau Cov Nyiaj Pab: HM thiab KK tau sau cov ntawv sau. Txhua tus kws sau ntawv tau nyeem thiab pom zoo rau cov ntawv luam tawm ntawm cov ntawv sau.
Cov Nyiaj Txiag: Txoj haujlwm no tau txais kev txhawb nqa los ntawm cov nyiaj pab los ntawm AMED (Grant Numbers JP19gm6110028 andJP19dm0107154 (HM)), Takeda Science Foundation (HM), JSPS KAKENHI (Grant NumbersJP 14516799 (HM), JP 1667490725) (HM) thiab JST [Moonshot R&D] [GrantNumber JPMJMS2024] (HM).
Institutional Review Board Statement: Tsis siv tau.
Cov Lus Qhia Txog Kev Pom Zoo: Tsis siv tau.
Daim Ntawv Qhia Txog Cov Ntaub Ntawv: Cov ntaub ntawv thiab cov cuab yeej tau piav qhia hauv phau ntawv no muaj nyob rau thaum thov.
Kev lees paub: Peb lees paub Shinano Kobayashi thiab Noriko Matsui rau kev koom nrog kev sib tham tsis muaj txiaj ntsig thiab muab kev txhawb nqa tas mus li. Peb lees paub Ai Ito rau nws txoj haujlwm ntawm cov duab kos.
Kev tsis sib haum xeeb ntawm kev txaus siab: Cov neeg sau ntawv tshaj tawm tsis muaj teeb meem ntawm kev txaus siab.
Cov ntaub ntawv
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