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Nejrohimiya galuz himiyi ta rozdil nejronauki sho zoseredzhuyetsya na vivchenni rechovin i himichnih procesiv sho mistyatsya i vidbuvayutsya v nervovij sistemi Ce mizhdisciplinarna sfera yaka vklyuchaye v sebe elementi biohimiyi nejrofiziologiyi ta farmakologiyi shob zrozumiti yak mozok i nervova sistema funkcionuyut na molekulyarnomu rivni Nikotinovij acetilholinovij receptor u zakritomu stani z pokazanimi prognozovanimi mezhami membraniNejrohimiya zokrema zajmayetsya doslidzhennyam nejroaktivnih himichnih spoluk golovnim chinom nejromediatoriv i nejropeptidiv rechovin yaki vplivayut na funkciyi klitin ta sistem nervovoyi sistemi Osnovnim zavdannyam nejrohimiyi ye doslidzhennya togo yak nizkomolekulyarni organichni spoluki vplivayut na funkcionuvannya nejronnih merezh i nervovoyi sistemi v cilomu Nejrohimiya takozh fokusuyetsya na doslidzhenni roli organichnih spoluk u takih procesah yak nejroplastichnist nejrogenez diferenciaciya nervovih klitin sinaptogenez tosho Nejrohimiya vidigraye vazhlivu rol u rozuminni togo yak pracyuye mozok zokrema yak vin obroblyaye informaciyu regulyuye povedinku ta kontrolyuye funkciyi organizmu Cya galuz maye znachni naslidki dlya medicini ta suspilstva oskilki vona daye rozuminnya rozvitku ta likuvannya nevrologichnih rozladiv a takozh vidkrittya ta rozrobku novih likiv 1 Zmist 1 Istoriya 2 Predmet doslidzhennya 2 1 Nejromediatori 2 2 Receptori 2 3 Fermenti 3 Tehniki ta metodi 3 1 Mikrodializ 3 2 Visokoefektivna ridinna hromatografiya 3 3 Imunogistohimiya 3 4 Nejrovizualizaciya 3 5 Elektrofiziologiya 3 6 Analiz ekspresiyi geniv 4 Perspektivni tehnologiyi 5 Div takozh 6 Primitki 7 Literatura 7 1 Knigi 7 2 ZhurnaliIstoriya RedaguvatiIstoriyu nejrohimiyi mozhna prostezhiti do 19 stolittya koli vcheni vpershe pochali identifikuvati ta vidilyati himichni rechovini v nervovij sistemi Odna z peredumov cogo bula u 1806 roci koli italijskij likar Luyidzhi Galvani viyaviv sho elektrichna stimulyaciya m yaziv zhabi mozhe buti vikoristana dlya imitaciyi potencialu diyi nervovoyi sistemi Ce prizvelo do rozuminnya togo sho nervova sistema ye elektrichno zbudlivoyu sistemoyu i proklalo shlyah do vivchennya himichnoyi osnovi nervovoyi signalizaciyi 2 Naprikinci 1800 h rokiv doslidniki pochali identifikuvati specifichni himichni rechovini v nervovij sistemi taki yak acetilholin yakij vidkriv nimeckij fiziolog Otto Levi v 1921 roci Vidkrittya Levi roli acetilholinu v peredachi nervovih signaliv prineslo jomu Nobelivsku premiyu z fiziologiyi ta medicini v 1936 roci 3 Doslidzhennya nejromediatoriv prodovzhilo rozvivatisya v seredini 20 go stolittya z vidkrittyam inshih osnovnih nejromediatoriv takih yak dofamin serotonin i noradrenalin Ci vidkrittya proklali shlyah dlya rozrobki likiv yaki nacileni na konkretni nejromediatorni sistemi yaki zrobili revolyuciyu v likuvanni psihichnih rozladiv Nejrohimiya stala samostijnoyu galuzzyu doslidzhen u 1950 h rokah 4 Vidgaluzhennya nejrohimiyi u samostijnu naukovu disciplinu pochalosya z publikaciyi seriyi materialiv konferenciyi International Neurochemical Symposia pershij tom yakoyi opublikovanij u 1954 roci mav nazvu Biohimiya nervovoyi sistemi sho rozvivayetsya angl Biochemistry of the Developing Nervous System 5 Ci konferenciyi priveli do zasnuvannya Mizhnarodnogo tovaristva nejrohimiyi angl International Society for Neurochemistry a takozh Amerikanskogo tovaristva nejrohimiyi angl American Society for Neurochemistry Na zibrannyah cih tovaristv upershe obgovoryuvalas rol nejromediatoriv takih yak acetilholin gistamin serotonin u funkcionuvanni nervovoyi sistemi Udoskonalennya tehnologij napriklad rozrobka metodiv vimiryuvannya aktivnosti pevnih molekul u mozku ta keruvannya neyu pokrashili nashe rozuminnya nejrohimiyi Napriklad vinahid tehniki patch clamp u 1970 h rokah dozvoliv doslidnikam vimiryuvati elektrichnu aktivnist okremih nejroniv ta ionnih kanaliv sho prizvelo do znachnogo rozuminnya molekulyarnoyi osnovi nervovoyi signalizaciyi 6 7 Predmet doslidzhennya RedaguvatiNejromediatori Redaguvati DofaminNejromediatori nejrotransmiteri ce himichni poseredniki mesendzheri yaki zabezpechuyut zv yazok mizh nejronami nervovoyi sistemi Voni neobhidni dlya regulyuvannya bagatoh fiziologichnih procesiv takih yak ruh vidchuttya piznannya ta emociyi Nejromediatori sintezuyutsya vseredini nejrona i zberigayutsya u sinaptichnih puhircyah vezikulah poki ne vivilnyayutsya v sinaps u vidpovid na potencial diyi Pislya vivilnennya nejromediatori zv yazuyutsya zi specifichnimi receptorami na postsinaptichnomu nejroni abo inshih klitinah mishenyah m yazi zalozi zapuskayuchi kaskad biohimichnih podij yaki v kincevomu pidsumku prizvodyat do fiziologichnoyi reakciyi Glutaminergichnij sinapsIsnuye bagato riznih nejromediatoriv kozhen zi svoyimi unikalnimi funkciyami ta mehanizmami diyi Deyaki z najvidomishih nejromediatoriv vklyuchayut 1 Acetilholin ce nejromediator yakij bere uchast u kontroli motoriki ruhiv uvagi navchannya ta pam yati Ce takozh nejromediator yakij vikoristovuyetsya vegetativnoyu nervovoyu sistemoyu dlya regulyuvannya diyalnosti takih organiv yak serce legeni ta travna sistema Dofamin bere uchast u vinagorodi ta zadovolenni a takozh u kontroli motoriki ta motivaciyi Dofamin vidpovidaye za pragnennya ochikuvannya ta motivaciyu do chogo s sho poza tilom Vin takozh vazhlivo dlya regulyuvannya nastroyu ta piznannya Serotonin bere uchast u regulyaciyi nastroyu vidomij yak nejromediator radosti shastya apetitu ta snu Vin takozh vazhlivij dlya regulyuvannya bolyu ta agresiyi Noradrenalin bere uchast u reakciyi bijsya abo vtechi a takozh zbudzhuye uvagu ta pidsilyuye fokus GAMK bere uchast u galmuvanni nejronnoyi aktivnosti Ce vazhlivo dlya regulyuvannya nadmirnogo zbudzhennya klitin ta nejronnih lancyugiv i dlya kontrolyu trivozhnosti ta snu Glutamat bere uchast v aktivaciyi nervovoyi diyalnosti Glutamat ye osnovnim zbudzhuyuchim nejromediatorom mozku Vin vazhlivij dlya navchannya ta pam yati a takozh dlya regulyuvannya nastroyu Porushennya regulyaciyi nejromediatornih sistem mozhe prizvesti do riznomanitnih nevrologichnih i psihichnih rozladiv vklyuchayuchi hvorobu Parkinsona depresiyu ta shizofreniyu Tomu rozuminnya mehanizmiv sho lezhat v osnovi funkciyi ta disfunkciyi nejromediatoriv maye virishalne znachennya dlya rozrobki metodiv likuvannya cih rozladiv Receptori Redaguvati Receptori ce bilki roztashovani na poverhni klitin yaki zv yazuyutsya z nejromediatorami ta inshimi signalnimi molekulami Voni vidigrayut virishalnu rol u oposeredkuvanni efektiv nejromediatoriv iniciyuyuchi seriyu vnutrishnoklitinnih signalnih podij yaki v kincevomu pidsumku prizvodyat do fiziologichnoyi reakciyi Rozriznyayut dva osnovnih tipi receptoriv ionotropni ta metabotropni Ionotropni receptori ye shvidkodiyuchimi i bezposeredno vidkrivayut abo zakrivayut ionni kanali v membrani postsinaptichnogo nejrona sho prizvodit do shvidkoyi zmini membrannogo potencialu Metabotropni receptori z inshogo boku diyut povilnishe ta oposeredkovano aktivuyut vnutrishnoklitinni signalni shlyahi sho prizvodit do bilsh trivalih efektiv Ligand zalezhnij ionnij kanalIsnuye bagato riznih tipiv receptoriv kozhen zi svoyimi specifichnimi funkciyami ta harakteristikami Deyaki z najbilsh vidomih receptoriv vklyuchayut 1 Receptori pov yazani z G bilkom GPCR najbilshe simejstvom receptoriv yaki berut uchast u shirokomu spektri fiziologichnih procesiv takih yak zir nyuh i smak Voni takozh ye vazhlivimi mishenyami dlya bagatoh likiv Ligand zalezhni ionni kanali ci receptori bezposeredno vidkrivayut abo zakrivayut ionni kanali u vidpovid na zv yazuvannya nejromediatora Prikladi vklyuchayut nikotinovij receptor acetilholinu ta receptor NMDA Receptori tirozinkinazi ci receptori berut uchast u zrostanni ta diferenciaciyi klitin Prikladi vklyuchayut receptor epidermalnogo faktora rostu ta receptor insulinu Yaderni receptori Ci receptori roztashovani vseredini klitini ta berut uchast u regulyaciyi ekspresiyi geniv Prikladi vklyuchayut receptor estrogenu ta receptor vitaminu D Anomaliyi funkciyi receptoriv pov yazani z riznimi zahvoryuvannyami vklyuchayuchi diabet i nevrologichni rozladi taki yak hvoroba Alcgejmera ta epilepsiya ta onkopatologiyi Tomu rozuminnya strukturi ta funkciyi receptoriv maye vazhlive znachennya dlya rozrobki novih metodiv likuvannya cih staniv Fermenti Redaguvati Fermenti ce bilki yaki katalizuyut biohimichni reakciyi v organizmi v tomu chisli berut uchast u sintezi nejromediatoriv i metabolizmi Fermenti vidigrayut virishalnu rol u regulyuvanni kilkosti nejromediatoriv u sinapsi a porushennya funkciyi fermentiv mozhut prizvesti do disbalansu v peredachi signaliv nejromediatorami U metabolizmi nejromediatoriv bere uchast bagato riznih fermentiv zokrema 1 Monoaminoksidaza MAO ce ferment yakij rozsheplyuye nejromediatori monoamini taki yak dofamin noradrenalin i serotonin 8 9 Ingibitori MAO vikoristovuyutsya zokrema yak antidepresanti 10 Acetilholinesteraza AChE ce ferment yakij rujnuye nejromediator acetilholin pripinyayuchi jogo peredachu signaliv 11 12 13 14 15 Ingibitori acetilholinesterazi vikoristovuyutsya zokrema dlya likuvannya hvorobi Alcgejmera 16 17 Dekarboksilaza aromatichnih L aminokislot AADC ferment yakij peretvoryuye L DOPA v dofamin L DOPA ce himichna spoluka i preparat yakij vikoristovuyetsya dlya likuvannya hvorobi Parkinsona yaka sprichinena deficitom dofaminu v nejronnih lancyugah mozku 18 19 20 Tirozingidroksilaza TH ce ferment yakij peretvoryuye aminokislotu tirozin v L DOPA yakij potim peretvoryuyetsya na dofamin 21 22 Ingibitori tirozinkinazi vikoristovuyutsya zokrema dlya likuvannya onkopatologij 23 Glutamatdekarboksilaza GAD ce ferment yakij peretvoryuye nejromediator glutamat na GAMK sho vazhlivo dlya galmuvannya nejronnoyi aktivnosti 24 Ingibitori GAD doslidzhuyutsya yak potencijni zasobi likuvannya trivozhnih ta epileptichnih rozladiv 25 26 Porushennya regulyaciyi funkciyi fermentiv mozhe prizvesti do riznomanitnih nevrologichnih i psihichnih rozladiv vklyuchayuchi hvorobu Parkinsona depresiyu ta trivogu Tomu rozuminnya mehanizmiv sho lezhat v osnovi funkciyi ta disfunkciyi fermentiv maye vazhlive znachennya dlya rozrobki metodiv likuvannya cih rozladiv Tehniki ta metodi RedaguvatiNejrohimiya vklyuchaye vivchennya himichnih procesiv i molekul yaki zabezpechuyut funkcionuvannya nervovoyi sistemi Isnuye kilka metodiv yaki vikoristovuyutsya v nejrohimiyi dlya doslidzhennya himichnogo skladu funkciyi ta regulyaciyi nervovoyi sistemi Ci metodi sered inshogo vidigrayut virishalnu rol u vdoskonalenni nashogo rozuminnya nervovoyi sistemi ta roli nejrohimiyi v zdorov yi ta hvorobah Vikoristovuyuchi ci metodi doslidniki mozhut otrimati cinnu informaciyu pro molekulyarni mehanizmi sho lezhat v osnovi nevrologichnih i psihichnih rozladiv i rozrobiti novi metodi likuvannya dlya paciyentiv 1 Mikrodializ Redaguvati Mikrodializ ce metod yakij vikoristovuyetsya dlya vzyattya zrazkiv pozaklitinnoyi ridini v golovnomu abo spinnomu mozku Nevelikij zond z napivproniknoyu membranoyu vstavlyayetsya v mozok i ridina perfuzuyetsya cherez zond Cej metod dozvolyaye doslidnikam vimiryuvati rivni nejromediatoriv metabolitiv ta inshih spoluk u pozaklitinnij ridini 27 Visokoefektivna ridinna hromatografiya Redaguvati Visokoefektivna ridinna hromatografiya HPLC VERH ce tehnika yaka vikoristovuyetsya dlya rozdilennya identifikaciyi ta kilkisnogo viznachennya riznih spoluk u zrazku VERH chasto vikoristovuyetsya v nejrohimiyi dlya vimiryuvannya rivniv nejromediatoriv nejropeptidiv ta inshih malih molekul u zrazkah tkanin 28 29 30 Imunogistohimiya Redaguvati Mienterialnij ganglij mishi z tirozingidroksilazoyu poznachaye simpatichni vegetativni aksoni poznachenij imunogistohimichnim metodom zelenij otrimanij za dopomogoyu lazernogo skanuvalnogo konfokalnogo mikroskopa Sinij kolir ce autofluorescenciya v UF diapazoni postganglionarnih nejroniv Imunogistohimiya ce tehnika yaka vikoristovuyetsya dlya vizualizaciyi specifichnih molekul takih yak nejromediatori receptori ta fermenti u zrazkah tkanin Antitila yaki zv yazuyutsya z pevnimi molekulami pomicheni fluorescentnim abo fermentativnim markerom sho dozvolyaye vizualizuvati yih pid mikroskopom 31 32 Nejrovizualizaciya Redaguvati Pozitronno emisijna tomografiya PET 33 34 i odnofotonna emisijna komp yuterna tomografiya OFEKT 35 36 ce metodi nejrovizualizaciyi yaki vikoristovuyutsya dlya vimiryuvannya rivniv nejromediatoriv receptoriv ta inshih molekul u mozku Radioindikatori yaki micheni radioaktivnim izotopom vvodyatsya v krov i yih rozpodil u mozku vimiryuyetsya za dopomogoyu specialnih kamer Elektrofiziologiya Redaguvati Elektrofiziologiya ce metod yakij vikoristovuyetsya dlya vimiryuvannya elektrichnoyi aktivnosti nejroniv u golovnomu ta spinnomu mozku Cej metod peredbachaye vvedennya nevelikogo elektroda v tkaninu ta vimiryuvannya elektrichnih signaliv sho generuyutsya nejronami 37 Analiz ekspresiyi geniv Redaguvati Analiz ekspresiyi geniv ce tehnika yaka vikoristovuyetsya dlya vimiryuvannya rivniv riznih geniv u nervovij sistemi Ce mozhe dati uyavlennya pro molekulyarni mehanizmi sho lezhat v osnovi nevrologichnih i psihiatrichnih rozladiv 38 39 Perspektivni tehnologiyi RedaguvatiMajbutnye nejrohimiyi bagatoobicyayuche oskilki postijni doslidzhennya ta progres u tehnologiyi dozvolyayut krashe zrozumiti skladnu vzayemodiyu mizh nejronami ta nejromediatorami Os deyaki z potencijnih sfer rozvitku v galuzi Nejroproteomika proteomika ce vivchennya povnogo naboru bilkiv u klitini chi organizmi U nejrohimiyi nejroproteomika vklyuchaye vivchennya bilkiv yaki berut uchast u nejronnomu zv yazku ta sinaptichnij funkciyi Ochikuyetsya sho cej pidhid dast novi znannya pro mehanizmi sho lezhat v osnovi nevrologichnih rozladiv i mozhe prizvesti do vidkrittya novih likarskih cilej 40 41 42 Modelyuvannya bilkiv za dopomogoyu shtuchnogo intelektu AlphaFold vid DeepMind na kinec 2022 roku vdalos rozshifruvati strukturu 214 miljoniv bilkiv Ce znachnij krok v rozuminni foldingu bilku i vin vidkrivaye veliki mozhlivosti dlya sintezu novih likiv dlya likuvannya nevrologichnih i ne tilki rozladiv 43 Nanotehnologiyi vikoristannya nanotehnologij u nejronaukah ye novoyu sferoyu doslidzhen yaka mozhe revolyucionizuvati nashe rozuminnya mozku ta jogo funkcionuvannya Instrumenti nanotehnologij taki yak nanosensori ta nanoroboti mozhna vikoristovuvati dlya vivchennya aktivnosti okremih nejroniv ta yihnih zv yazkiv sho dozvolyaye z bilshoyu tochnistyu vimiryuvati vivilnennya ta poglinannya nejromediatoriv 44 45 46 47 Div takozh Biomolekulyarna elektronika Sistemna nejronauka tehnologichnij progres i obchislyuvalna potuzhnist dozvolyayut vivchati skladni nejronni shemi z bezprecedentnim rivnem detalizaciyi Ochikuyetsya sho cej pidhid prizvede do glibshogo rozuminnya mehanizmiv sho lezhat v osnovi funkcionuvannya mozku na rivni nejronnih lancyugiv ta yih merezh i zreshtoyu mozhe prizvesti do rozrobki novih metodiv likuvannya nevrologichnih rozladiv 48 42 Nejrofarmakologiya ce vivchennya vplivu likiv na nervovu sistemu kriz prizmu farmakologiyi Zi zrostannyam rozuminnya mehanizmiv sho lezhat v osnovi nevrologichnih rozladiv ye potencial dlya rozrobki bilsh cilespryamovanih i efektivnih metodiv likuvannya Zagalom majbutnye nejrohimiyi zahoplyuyuche z novimi dosyagnennyami v tehnologiyi ta metodah doslidzhennya yaki dozvolyayut krashe zrozumiti mozok i jogo funkciyi Ochikuyetsya sho ci rozrobki prizvedut do novih metodiv likuvannya nevrologichnih rozladiv i zreshtoyu pokrashat yakist zhittya tih hto strazhdaye vid cih zahvoryuvan chi zastosovuvatimutsya v udoskonalenni lyudini Div takozh RedaguvatiMolekulyarna nejronauka Klitinna nejronauka Nejroplastichnist Signalna transdukciya NejronaukaPrimitki Redaguvati a b v g d Brady Scott T Siegel George J Albers R Wayne Price D L Benjamins Joyce 2012 Basic neurochemistry principles of molecular cellular and medical neurobiology vid Eighth edition 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