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Nejrogenez ce proces za dopomogoyu yakogo klitini nervovoyi sistemi nejroni viroblyayutsya nervovimi stovburovimi klitinami NSK Prisutnij u vsih vidiv tvarin za vinyatkom poriferi gubok i plakozoidnih 2 Model nejrogenezu ssavciv 1 Zubchasta zvivina gipokampu molodih mishej Pofarbovani v zelenij kolir nervovi stovburovi klitini a v chervonij astrociti sho yih otochuyut Nervovi klitini poperedniki A Nejrosfera sho skladayetsya z klitin subventrikulyarnoyi zoni vidilenih na E15 yaki agreguvali v suspenziyi pislya 2 dniv kultivuvannya B Nejrosfera klitin SVZ otrimanih na E15 yaki prikripilisya do dna kulturalnoyi kolbi pislya 4 dniv kultivuvannya C Dlya elektrofiziologichnogo zapisu buli obrani klitini na periferiyi nejrosfer Tipi NSK vklyuchayut nejroepitelialni klitini NEC radialni glialni klitini RGC bazalni klitini poperedniki BP promizhni poperedniki nejroniv INP astrociti subventrikulyarnoyi zoni ta radialni astrociti subgranulyarnoyi zoni sered inshih 2 Nejrogenez najbilsh aktivnij pid chas embrionalnogo rozvitku i vidpovidaye za virobnictvo vsih riznih tipiv nejroniv organizmu ale vin prodovzhuyetsya protyagom usogo doroslogo zhittya v riznih organizmah 2 Pislya narodzhennya nejroni ne dilyatsya div mitoz i bagato z nih prozhivut protyagom vsogo zhittya tvarini za vinyatkom nadzvichajnih i zazvichaj patogennih obstavin 3 Zmist 1 Nejrogenez u ssavciv 1 1 Nejrogenez rozvitku 1 1 1 Epigenetichna modifikaciya 1 2 Nejrogenez v doroslih 1 2 1 Subventrikulyarnaya zona 1 2 2 Gipokamp 1 3 Faktori sho vplivayut na nejrogenez doroslih 1 3 1 Pokrashuyut 1 3 2 Pogirshuyut 2 Indukovanij nejrogenez 3 Nejrogenez v inshih organizmah 4 Inshi doslidzhennya 5 Aktualnist 6 Divis takozh 7 Dodatkova literatura 7 1 Knigi 7 2 Statti 8 Posilannya 9 PrimitkiNejrogenez u ssavciv RedaguvatiNejrogenez rozvitku Redaguvati Pid chas embrionalnogo rozvitku centralna nervova sistema ssavciv CNS golovnij i spinnij mozok utvoryuyetsya z nervovoyi trubki yaka mistit NSK yaki piznishe generuvatimut nejroni 3 Odnak nejrogenez ne pochinayetsya poki ne bude dosyagnuto dostatnoyi populyaciyi NSK Ci ranni stovburovi klitini nazivayutsya nejroepitelialnimi klitinami NEC ale nezabarom voni nabuvayut silno vityagnutoyi radialnoyi morfologiyi i potim vidomi yak radialni glialni klitini RGC 3 RGK ye pervinnimi stovburovimi klitinami CNS ssavciv i znahodyatsya v embrionalnij shlunochkovij zoni yaka prilyagaye do centralnoyi zapovnenoyi ridinoyu porozhnini shlunochkovoyi sistemi nervovoyi trubki 4 5 Pislya proliferaciyi RGC nejrogenez vklyuchaye ostatochnij podil klitini batkivskogo RGC sho prizvodit do odnogo z dvoh mozhlivih rezultativ Po pershe ce mozhe stvoriti pidklas nejronnih poperednikiv yaki nazivayutsya promizhnimi nejronnimi poperednikami INP yaki budut dilitisya odin abo kilka raziv dlya virobnictva nejroniv Alternativno dochirni nejroni mozhut viroblyatisya bezposeredno Nejroni ne utvoryuyut vidrazu nejronni lancyugi cherez zrostannya aksoniv i dendritiv Natomist novonarodzheni nejroni povinni spochatku migruvati na veliki vidstani do kincevogo punktu priznachennya dozrivayuchi ta nareshti generuyuchi nejronni lancyugi shemi Napriklad nejroni sho narodzhuyutsya v zoni shlunochkiv radialno migruyut do kortikalnoyi plastinki de nakopichuyutsya utvoryuyuchi koru golovnogo mozku 4 5 Takim chinom generaciya nejroniv vidbuvayetsya v pevnomu viddili tkanini abo nejrogennij nishi zajnyatij yih batkivskimi stovburovimi klitinami Shvidkist nejrogenezu ta tip generovanogo nejrona zbudlivij abo galmivnij v osnovnomu viznachayutsya molekulyarnimi ta genetichnimi faktorami Ci faktori zokrema vklyuchayut signalnij shlyah Notch i bagato geniv buli pov yazani z regulyaciyeyu shlyahu Notch 6 7 Geni ta mehanizmi zadiyani v regulyaciyi nejrogenezu ye predmetom intensivnih doslidzhen v akademichnih farmacevtichnih ta derzhavnih ustanovah u vsomu sviti Chas neobhidnij dlya generaciyi vsih nejroniv CNS u riznih ssavciv silno vidriznyayetsya i nejrogenez mozku ne zavzhdi zavershuyetsya do momentu narodzhennya 3 Napriklad mishi piddayutsya kortikalnomu nejrogenezu priblizno z dnya embriona den pislya zachattya E11 do E17 i narodzhuyutsya priblizno v E19 5 8 Thori narodzhuyutsya na E42 hocha yih period kortikalnogo nejrogenezu zakinchuyetsya lishe cherez kilka dniv pislya narodzhennya 9 Nejrogenez u lyudej zazvichaj pochinayetsya priblizno na 10 mu gestacijnomu tizhni i zakinchuyetsya priblizno na 25 mu z narodzhennyam priblizno na 38 40 mu 10 Epigenetichna modifikaciya Redaguvati U miru embrionalnogo rozvitku mozku ssavciv nervovi klitini poperedniki ta stovburovi klitini peremikayutsya z proliferaciyi na diferenciaciyu Ce progresuvannya prizvodit do generaciyi nejroniv i gliyi yaki zapovnyuyut kortikalni shari Epigenetichni modifikaciyi vidigrayut klyuchovu rol u regulyaciyi ekspresiyi geniv u klitinnij diferenciaciyi nervovih stovburovih klitin Epigenetichni modifikaciyi vklyuchayut metilyuvannya citozinu DNK z utvorennyam 5 metilcitozinu ta demetilyuvannya 5 metilcitozinu 11 12 Ci modifikaciyi mayut virishalne znachennya dlya viznachennya doli klitin u mozku ssavciv sho rozvivayetsya i doroslih Metilyuvannya citozinu DNK katalizuyetsya DNK metiltransferazami DNMT Demetilyuvannya metilcitozinu katalizuyetsya v kilka etapiv fermentami TET yaki zdijsnyuyut okisni reakciyi napriklad 5 metilcitozin do 5 gidroksimetilcitozinu i fermentami shlyahu ekscizijnoyi reparaciyi osnovi DNK 11 Nejrogenez v doroslih Redaguvati Nejrogenez mozhe buti skladnim procesom u deyakih ssavciv Napriklad u grizuniv nejroni v centralnij nervovij sistemi vinikayut iz troh tipiv nejronnih stovburovih klitin i klitin poperednikiv nejroepitelialnih klitin radialnih glialnih klitin i bazalnih klitin poperednikiv yaki prohodyat cherez tri osnovni viddili simetrichnij proliferativnij viddil asimetrichnij nejrogennij viddil i simetrichnij nejrogennij viddil Z usih troh tipiv klitin nejroepitelialni klitini yaki prohodyat cherez nejrogenni viddili mayut nabagato bilsh rozshirenij klitinnij cikl nizh ti yaki prohodyat cherez proliferativni podili taki yak radialni glialni klitini ta bazalni klitini poperedniki 13 Bulo pokazano sho u lyudini nejrogenez dorosloyi lyudini vidbuvayetsya menshe porivnyano z periodom rozvitku nervovoyi sistemi i perevazhno v troh oblastyah mozku dorosla subventrikulyarna zona SVZ bichnih shlunochkiv migdalepodibne tilo ta zubchasta zvivina gipokampu 14 15 16 17 18 hocha doslidzhennya pislya 2020 r pidtverdzhuyut nejrogenez doroslih u inshih regionah mozku 19 20 Doslidzhennya v sferi odnoklitinnoyi transkriptomiki nejroniv gipokampa namagayutsya zrozumiti cej proces na molekulyarnomu rivni 21 Ingibuvannya kinazi ROCK zmenshuye spajki v aktivovanih proliferativnih NSK vidnovlyuye migraciyu v starih aktivovanih NSK in vitro ta posilyuye nejrogenez in vivo 22 Subventrikulyarnaya zona Redaguvati nbsp Anatomiya nejrogennoyi subventrikulyarnoyi zoni golovnogo mozku doroslogo grizuna ta lyudini C Bazalni gangliyi ta bichni shlunochki D Shematichnij malyunok sho zobrazhuye klitinnij sklad i citoarhitekturu subventrikulyarnoyi zoni dorosloyi lyudini sho skladayetsya z chotiroh shariv shar I shar ependimalnih klitin zelenij shar II gipocelyulyarna shilina shar III astrocitarna strichka sho mistit astrociti ta migruyuchi nejroblasti IV shar perehidna zona sho mistit oligodendrociti i vidokremlyuye SVZ vid bagatogo nejronami smugastogo tila U bagatoh ssavciv u tomu chisli grizuniv nyuhova cibulina ce dilyanka mozku sho mistit klitini yaki sprijmayut zapahi z integraciyeyu nejroniv doroslogo pohodzhennya yaki migruyut iz subventrikulyarnoyi zoni smugastogo tila do nyuhovoyi cibulini cherez rostralnij migracijnij potik RMS 16 23 Migruyuchi nejroblasti v nyuhovij cibulini stayut internejronami yaki dopomagayut mozku spilkuvatisya z cimi sensornimi klitinami Bilshist cih internejroniv ye galmivnimi zernistimi klitinami ale nevelika kilkist ye periglomerulyarnimi klitinami U doroslih subventrikulyarnih zonah pervinnimi nejronnimi stovburovimi klitinami ye astrociti subventrikulyarnoyi zoni a ne radialni glialni klitini RGC Bilshist cih doroslih nervovih stovburovih klitin perebuvayut u stani spokoyu u dorosloyi lyudini ale u vidpovid na pevni signali ci splyachi klitini abo V klitini prohodyat ryad stadij spochatku viroblyayuchi proliferuyuchi klitini abo S klitini Potim S klitini viroblyayut nejroblasti abo A klitini yaki stanut nejronami 17 Gipokamp Redaguvati Znachnij nejrogenez takozh vidbuvayetsya v doroslomu vici v gipokampi bagatoh ssavciv vid grizuniv do deyakih primativ 24 25 26 Gipokamp vidigraye virishalnu rol u formuvanni novih deklarativnih spogadiv i isnuye teoriya pro te sho prichina chomu nemovlyata ne mozhut sformuvati deklarativni spogadi polyagaye v tomu sho voni vse she zaznayut intensivnogo nejrogenezu v gipokampi a yihni shemi generuvannya pam yati ye nezrilimi 27 Povidomlyalosya sho bagato faktoriv navkolishnogo seredovisha taki yak fizichni vpravi zvichki harchuvannya navchannya zbilshuyut shvidkist nejrogenezu v gipokampi lyudej 28 ta grizuniv 29 30 Faktori sho vplivayut na nejrogenez doroslih Redaguvati Deyaki faktori ta zvichki vplivayut na aktivnist nejrogenezu v mozku doroslih 31 Pokrashuyut Redaguvati nbsp Voloskij gorih dzherelo Omega 3 zhirnih kislot Racionalne harchuvannya 32 vzhivannya Omega 3 zhirnih kislot chornici ta inshih bagatih na flavonoyidi produktiv kurkuminu cinku foliyevoyi kisloti rezveratrolu Intervalne goloduvannya 33 ta inshi metodi obmezhennya kalorazhu Fizichna aktivnist sho pokrashuye krovopostachannya mozku big ta inshi vidi aerobnoyi aktivnosti 34 Pogirshuyut Redaguvati Vzhivannya alkogolyu Nadmirne vzhivannya cukru ta nasichenih zhirnih kislot Deficit vitaminu A vitaminiv grupi B vitaminu E Deficit harchovih volokon v racioni Porushennya mikrobioti antibiotikami 35 Indukovanij nejrogenez RedaguvatiOsnovni strategiyi pidvishennya endogennogo nejrogenezu zokrema dlya likuvannya travm chi starinnya vklyuchayut 36 Farmakologichnij vpliv DMT u veresni 2020 roku doslidzhennya in vitro ta in vivo pokazali sho DMT prisutnij u nastoyi ayauaski spriyaye nejrogenezu 37 Psilocibin doslidzhennya pokazalo sho nizka doza 0 1 mg kg psilocibinu yakij vvodili mishi posilyuye nejrogenez u gipokampi navit cherez 2 tizhni pislya vvedennya todi yak visoka doza 1 mg kg znachno znizhuye nejrogenez 38 Kanabinoyidi u doroslomu mozku endokanabinoyidna sistema spriyaye nejrogenezu zernistih klitin gipokampa Aktivaciya kanabinoyidnih receptoriv CB1 endogennimi abo ekzogennimi kannabinoyidami spriyaye proliferaciyi ta diferenciaciyi nejronnih stovburovih klitin cya aktivaciya vidsutnya pri nokauti CB1 i skasovuyetsya v prisutnosti antagonista 39 40 41 She odne doslidzhennya pokazalo sho sintetichnij kanabinoyid HU210 spriyaye proliferaciyi nejronnih stovburovih klitin gipokampa yak v embrionalnih tak i v doroslih shuriv sho prizvodit do posilennya nejrogenezu v zubchastij zvivini gipokampa Ce zbilshennya nejrogenezu korelyuvalo z anksiolitichnimi ta antidepresantnimi efektami u doroslih shuriv sho svidchit pro te sho kanabinoyidi mozhut mati potencial regulyuvati nejrogenez i vplivati na povedinku 42 Ingibitori GSK 3 Glikogensintaza kinaza 3 43 Genoterapiyu 44 ta redaguvannya genoma 45 zokrema pereprogramuvannya in vivo reaktivnih astrocitiv 46 i NG2 gliyi 47 Gormoni 48 faktori rostu BDNF 41 NGF GDNF ta in 49 ta inshi gumoralni faktori 50 Zmenshennya nejrozapalennya 51 Vpliv fizichnih faktoriv elektromagnitnij 52 ta ultrazvukovij 53 vpliv mozhe stimulyuvati aktivaciyu stovburovih klitin CNSNejrogenez v inshih organizmah RedaguvatiNejrogenez najkrashe oharakterizovano v modelnih organizmah takih yak plodova mushka Drosophila melanogaster Nejrogenez u cih organizmiv vidbuvayetsya v oblasti kori golovnogo mozku yih zorovih chastok Ci organizmi mozhut buti modellyu dlya genetichnogo analizu nejrogenezu ta regeneraciyi mozku doroslih Bulo provedeno doslidzhennya v yakomu obgovoryuvalosya yak vivchennya reaguyuchih na poshkodzhennya klitin poperednikiv u drozofili mozhe dopomogti identifikuvati regenerativnij nejrogenez i yak znajti novi sposobi posilennya vidnovlennya mozku Neshodavno bulo provedeno doslidzhennya yake pokazalo yak u drozofili bulo viyavleno nejrogenez dorosloyi lyudini nizkogo rivnya zokrema v oblasti kori golovnogo mozku v yakomu nervovi poperedniki mozhut zbilshuvati virobnictvo novih nejroniv sho spriyaye nejrogenezu 54 55 56 U drozofili vpershe bulo opisano peredachu signaliv Notch yaka kontrolyuye proces peredachi signaliv vid klitini do klitini zvanij lateralnim ingibuvannyam u yakomu nejroni vibirkovo generuyutsya z epitelialnih klitin 57 58 Bulo takozh pokazano sho u deyakih hrebetnih vidbuvayetsya regenerativnij nejrogenez 59 Inshi doslidzhennya RedaguvatiYe dokazi togo sho novi nejroni viroblyayutsya v zubchastij zvivini gipokampu doroslih ssavciv oblasti mozku vazhlivoyi dlya navchannya motivaciyi pam yati ta emocij Doslidzhennya pokazalo sho novostvoreni klitini v gipokampi dorosloyi mishi mozhut demonstruvati vlastivosti pasivnoyi membrani potenciali diyi ta sinaptichni vhodi podibni do tih sho znahodyatsya v zrilih zubchastih granulovanih klitinah Ci znahidki svidchat pro te sho ci novostvoreni klitini mozhut dozrivati v bilsh praktichni ta korisni nejroni v mozku doroslih ssavciv 60 Ostanni doslidzhennya pidtverdzhuyut sho mikrogliya vstanovlyuye pryami kontakti z klitinnimi tilami nejroniv sho rozvivayutsya i cherez ci zv yazki regulyuye nejrogenez migraciyu integraciyu ta formuvannya nejronnih merezh 61 Aktualnist RedaguvatiHocha doslidzhennya nejrogenezu u doroslih na sogodnishnij den ye nedostatnimi doslidzhennya modelej na tvarinah pokazuyut sho nejrogenez potencijno vidigraye znachnu rol u vplivi na patogenez bagatoh nervovo psihichnih rozladiv 62 i nejrodegenerativnih kognitivnih disfunkciyi zokrema demenciya hvoroba Alcgejmera 63 Doslidzhennya na tvarinah pokazali korelyaciyu mizh rivnem gipokampalnogo 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