Bopaki ba Neurogenetic le Neuro bo nahanang ka mokhoa o nahanang oa Dopaminergic Contributions to Obesity (2015)

. Sengoloa se ngotsoeng; e fumaneha ho PMC 2016 Jul 1.

E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:

PMCID: PMC4474751

NIHMSID: NIHMS671333

Ansley Grimes Stanfill, PhD, RN,1,2 Yvette Conley, PhD,3 Ann Custom, PhD, RN, FAAN,4 Carol Thompson, PhD, DNP, ACNP, FNP, CCRN, FCCM, FAANP, FAAN,5 Ramin Homayouni, PhD,6 Patricia Cowan, PhD, RN,2 'me Donna Hathaway, PhD, RN, FAAN2

inahaneloang

Ha keketseho ea botena bo ntse e eketseha, lingaka le bafuputsi ka mokhoa o tšoanang ba batla litlhaloso tsa hore na ke hobaneng ha batho ba bang ba nona haholo ha ba bang ba sa. Le ha ho ja lijo tsa "caloric" le ho ikoetlisa ho hlile ho bapala karolo, batho ba bang ba ntse ba eketseha ka boima ba 'mele ho sa tsotelloe lintlha tsena. Bopaki bo ntseng bo eketseha bo fana ka maikutlo a hore liphatsa tsa lefutso li ka bapala karolo, 'me tlhaloso e le' ngoe e ka ba ho fetoha hoa liphatsa tsa lefutso liphatseng tsa methapo ea methapo ea methapo ea methapo. Ho fapana hona ho ka lebisa ho boiphihlelo bo sa lumellaneng le mehloli e metle ea lijo. Tlhahlobo ena ea lingoliloeng e hlahloba tsebo e atileng mabapi le kamano pakeng tsa botenya le litsela tsa moputso oa dopaminergic bokong, ka bopaki bo matla bo fanoeng ho tsoa ho neuroimaging le data ea neurogenetic. Lipatlisiso tse hatisitsoeng, Google Scholar, and Cumulative Index to Nursing and Allied Health Literature li ile tsa etsoa ka mantsoe a lipatlisiso dopamine, botenya, ho nona haholo, bokhoba ba lijo, libaka tsa boko tse amanang le mesocortical le mesolimbic (moputso) litseleng, le mefuta e loketseng ea dopaminergic le li-receptors. Lipolelo tsena li khutlisitse lingoloa tsa 200. Ntle le lingoliloeng tse 'maloa tsa sentinel, lingoloa li ile tsa phatlalatsoa pakeng tsa 1993 le 2013. Lintlha tsena li fana ka mohlala oa mohopolo oa botona bo totobatsang liphallelo tsa lefutso tsa dopaminergic hammoho le lintlha tse tloaelehileng tsa kotsi ea botenya, joalo ka demographics (lilemo, morabe, bong), ts'ebetso ea 'mele, lijo le meriana. Kutloisiso e khōloanyane ea lintho tse feto-fetohang tse bakang boima ba mmele le botenya li bohlokoa bakeng sa kalafo e sebetsang ea kliniki.

Keywords: dopamine, botenya, BMI, genetics

Ha keketseho ea botena bo ntse e eketseha, lingaka le bafuputsi ka mokhoa o tšoanang ba batla litlhaloso tsa hore na ke hobaneng ha batho ba bang ba nona haholo ha ba bang ba sa. Leha bothata bona bo ithutile haholo, karolo e kholo ea phapang ena e ntse e tlameha ho hlalosoa. Le ha ho ja lijo tsa "caloric" le ho ikoetlisa ho hlile ho bapala karolo, batho ba bang ba ntse ba eketseha ka boima ba 'mele ho sa tsotelloe lintlha tsena. Bopaki bo ntseng bo eketseha bo fana ka maikutlo a hore liphatsa tsa lefutso li ka bapala karolo, 'me tlhaloso e le' ngoe e ka ba ho fetoha hoa liphatsa tsa lefutso kahare ho tsela ea methapo ea methapo ea methapo. Lilemong tsa morao tjena re bone ho phatloha ha lingoliloeng ho hlahloba kamano ea dopamine le botena. Kamano ena e netefalitsoe ke data ea neurogenetic le neuroimaging mme e bonts'a ho ts'oana ha likokoana-hloko le likamanong tse bonoang ka mefuta e meng ea litlhahiso tse kang cocaine, joala le papali ea chelete.

Thutong ena ea lingoliloeng, re lekola tsebo e sa feleng mabapi le kamano pakeng tsa botenya le litsela tsa moputso oa dopaminergic bokong, ka bopaki bo matla bo fanoeng ho tloha neuroimaging le data ea neurogenetic. Re sebelisitse PubMed, Cumulative Index to Nursing and Allied Health Literature, le database tsa Google Scholar li batla litlaleho tse hlahlojoang ke lithaka tsa lipatlisiso ho batho le liphoofolo tse phatlalalitsoeng ka Senyesemane lilemong tse fetileng tsa 20, e leng nako e lekanang eo ho eona neurogenetic le neuroimaging masimo a tsebahala. Re sebelisitse mantsoe a patlo dopamine, botenya, ho nona haholo, bokhoba ba lijo, libaka tsa boko tse amanang le litselana tsa mesocortical le mesolimbic (moputso) (ke hore, bokaholimo ba sefahleho sa sefahleho sa sefahleho, bokellase ba bokapele, sebaka sa ho ikhula le ho thefuleha), le mefuta e loketseng ea dopaminergic le li-receptor, tse hlalositsoeng kamora nako. Lipolelo tsena li khutlisitse lingoloa tsa 200. Ntle le lingoliloeng tse 'maloa tsa sentinel, lingoloa li ile tsa phatlalatsoa pakeng tsa 1993 le 2013. Ho tsoa liphethong tsena, re fana ka tlhahiso ea mohopolo oa botena bo nkang lintlha tsa tlhaho tsa dopaminergic le tikoloho.

Background

Bothata ba Ho Nona Haholo

Ho latela Centers for Disease Control, lipakeng tsa 2007 le 2009, liketsahalo tsa ho nona haholo Amerika li eketsehile 1.1% (), ho bokella Maamerika a limilione a 2.4 a eketsehileng a ileng a kopana le sesosa sa botona (mmele index index [BMI] e kholo ho feta 30 kg / m2). Ho nona ke ntho e ka fetohang kotsi e nang le kamano e matla le li-comorbidities tse fapaneng, ho kenyeletsoa lefu la pelo le lefu la tsoekere. Ho feta moo, botenya (bo amanang le ho ja hampe le ho se ikoetlise ka matla a mmele) ke e 'ngoe ea lisosa tse etellang pele tsa lefu United States (). Litloaelo le setso sechabeng li bapala karolo ea kholo ea botona, empa likarolo tsa motho ke tsona tse tla khetholla hore na ke mang ea ke keng a nona maemong a joalo.

Ka kakaretso, boima ba 'mele bo lebisang ho botenya bo amahanngoa le ho ja lik'hilojule tse fetang tse sebelisitsoeng ho metabolism le ho ikoetlisa. Merero ea setso ea ho theola boima ba 'mele e kenyelletsa phokotso ea takatso ea lijo le keketseho ea palo ea likhalori tse sebelisitsoeng boikoetlisong. Leha ho le joalo, merero ena ea lijo ha e atlehe ho batho ba bangata. Maemong a mang, batho ba ba le phello ea "yo-yo", moo ba lulang leetong la nako e telele mme ba theole boima ba 'mele ebe ba e khutlisa kapele ha ba tlohela moralo, empa ba qalella ho potoloha hape. Bafuputsi ba bang ba boletse hore ba nang le bothata bo boholo taolong ea boima ba nako e telele ba ka fapana ka lefutso ho batho ba bang. Le ha botenya bo nkuoa e le pherekano ea polygenic, a mang a mefuta ena ea liphatsa tsa lefutso a ka fetoloa ke moputso oa neurotransmitter dopamine.

Karolo ea Dopamine

Bafuputsi haesale ba nka dopamine e le bohlokoa ho thuto ea botenya (). Le ha li-neurotransmitter tse ling tse ngata (joalo ka gamma-aminobutyric acid, glutamine, serotonin, le norepinephrine) li ka bapala karolo ea lijo, bopaki ba liteko bo bontša hore dopamine ke eona e atisang ho hlahisa moputso oa lijo hangata. ea pele e bonts'itse hore likhoto li tla hatella ka mokhoa o hlakileng lever ho amohela lits'ebetso tsa meputso ea dopaminergic ea likelello tsa bona. Liphumano tsena li hlahisitse tlhahiso ea pele ea hore ho lokolloa ha dopamine bokong ho tsamaisana le maikutlo a monate.

Maikutlo a monate a amanang le takatso ea lijo a boetse a tsamaisana le ho lokolloa ha dopamine (). Bathong ba nang le ts'ebetso e tloaelehileng ea ts'ebetso ea bona ea dopaminergic, lehaele e khuts'oane, joalo ka monko kapa pono, ea lijo tse tloaelehileng li ka qala ts'ebetso ea ho lokolla dopamine. Hang ha karabelo litabeng tsena e qala, motho ea tloaelehileng ea dopaminergically o lemoha boiphihlelo bohle ba ho ja e le bo khahlisang. Haholo-holo, lijo tse matlafatsoang haholo, joalo ka tse nang le tsoekere e ngata le mafura a mangata, li hlohlelletsa litseleng tsa dopaminergic ho feta lijo tse bobebe haholo ().

Ho lokolloa ha dopamine le hona ka tloaelo ho lebisa ho letsoalo kamora ho ja lijo, joalo ka ha ho bonts'itsoe ke Tsebiso ea hore haeba ho lokolloa ha dopamine ho thibetsoe ka lik'hemik'hale, lithuto li tlaleha ho eketseha ha takatso ea lijo. Motsoako ona oa lik'hemik'hale o hlaha ka kotloloho ha bakuli ba fuoa meriana ea antipsychotic, eo hangata e amanang le phaello ea boima ba 'mele (). Ntle le moo, ha maemo a dopamine ea synaptic e eketseha, takatso ea lijo ea fokotseha. Ketsahalo ena e etsahala le lingakeng ha bakuli ba beoa meriana e itseng bakeng sa phello ea khatello ea methapo 'me ho nahanoa hore e amana le ho thibeloa hoa mofuta oa "dopamine transporter 1 gene"DAT1; ). Ntle le moo, lipatlisiso li boetse li senotse kamano ena lipakeng tsa maemo a dopamine le phetoho mokhoeng oa ho ja ka mefuta ea liphoofolo. Likhoto tsa "ho li ja", tse hlahisoang ke ho thibeloa ha sucrose ka nako, li na le liphetoho maemong a dopamine, li-dopamine receptors, le mekhoa ea lipalangoang, ha li bapisoa le ba nang le phihlello ea ho setifise (; ; ).

Kahoo, mehlaleng ea preclinical le ea bongaka, tšitiso efe kapa efe ho leka-lekanang ea tsamaiso ea dopaminergic e ka lebisa mekhoeng e sa senyeheng ea ho ja. Ka lebaka leo, batho ba nang le liphetoho liphetoho tsamaisong ea bona ea dopaminergic ba ka ba le takatso e matla ea ho phahamisa maemo a bona a dopamine molemong oa ho fumana monate oa lijo. Le ha ho ka bonahala ho le thata, bafuputsi ba fane ka maikutlo a hore ho nona ho feta tekano ke teko ea motho ka mong ea ho iphetetsa bakeng sa karabelo e fokotsehileng ea dopaminergic (). Ho qeta nako e telele, ho nona ho feta tekano ho lebisa ho boima ba mmele le nts'etsopele ea botenya.

Dopaminergic Pathways

Dopamine e teng hohle bokong, empa e tsepamisitsoe litseleng tse 'ne tse kholo: tsela ea nigrostriatal, tsela ea tuberoinfundibular, tsela ea mesolimbic, le tsela ea mesocortical (). Tsela ea nigrostriatal e qala ho tloha ho nigra e kholo ho ea ho striatum, 'me e ikarabella haholo ho motsamao. Ha likarolo tsa tsela ena li sa sebetse, pherekano e baka lefu la Parkinson. Tsela ea tuberoinfundibular e kenyelletsa merero ea dopaminergic ho hypothalamus le gland ea pituitary, mme e bohlokoa bakeng sa nts'etsopele le taolo ea prolactin ea hormone. Leha ho le joalo, lipatlisiso ha li bonts'e e 'ngoe ea litsela tsena tse amanang le botenya haholo. Ho fapana le moo, mesolimbic le mesocortical pathways, e tsejoang e le "meputso ea meputso," e kenyelletsa libaka tsa dopaminergic tse amanang le ho se tsitse, boitšoaro, le maikutlo a monate a amanang le boits'oaro bo bobebe mme bo amana haholo le botenya. Bakeng sa setšoantšo se qaqileng haholoanyane sa ts'ebetso ea litsela tsohle tse 'ne tsa dopaminergic le setšoantšo sa merero, ka kopo bona .

Kamano ea Dopamine le botenya e amahanngoa le tsela ea mesolimbic, e simolohang sebakeng sa sepheo sa likarolo tsa moea le merero ho li-bokellase tsa nucleus. Libaka tsena li bohareng ba bohareng ba bobe mme re ka thoko ho taolo ea rona. Ha re sebetsana le maemo a amanang le tlala (ka karolo e tsamaisoang ke lihormone tse kang ghrelin, leptin, le insulin), ketsahalo ea li-dopaminergic neurons e sebakeng sa "ventral tegmental" e eketsehang (). Merero ea mesocortical pathway e tsoang sebakeng sa tefo ea ventral ho ea lintlheng tse phahameng tsa ho beha mabaka ka cortex ea 'mele e laolang moputso le tšusumetso. Ka tloaelo, litsela tse peli li kopantsoe 'me li bitsoa tsela ea mesolimbocortical ka lebaka la kamano e haufi pakeng tsa meputso ea meputso le maikutlo a monate. Patlisiso e bontšitse tsela ea mesolimbocortical e amanang le mefuta e mengata ea boiphihlelo bo khotsofatsang, empa e amana haholo le menyako ea mantlha e kang thobalano le lijo ebile e sa amaneng haholo le menyako e holimo ea menyaka joalo ka menyaka ea chelete, boithati le boithabiso.).

Bopaki ba Neuroimaging bakeng sa Kamano lipakeng tsa Botenya le Dopaminergic Reward Pathways

Neuroimaging e fana ka sesebelisoa sa bohlokoa sa ho ithuta botenya ka lebaka la bokhoni ba eona ba ho tseba libaka tsa boko tse kenyelletsoang boits'ebetsong ba ho ja. Haholo-holo, datha ea ts'ebetso ea matla a makenete e sebetsang e bohlokoa hobane e bonts'a libaka tse phallo ea mali (ke hore, libaka tse qalileng) nakong ea mesebetsi e itseng. Mohlala, "insula" le "striatum" hangata li koaheloa nakong ea ha ho hlahisoa mekhoa ea lijo (). Amygdala e kenngoa nakong ea lijo, mohlomong ka lebaka la maikutlo a nepahetseng a amanang. Ho feta moo, bafuputsi ba lumela hore mohopolo oa ho hopola le boiphihlelo ka lijo o kenya letsoho hippocampus (). Neuroimaging e boetse e lumella ho bapisoa ha mekhoa ea ts'ebetso lipakeng tsa batho ba motenya le ba tloaelehileng ha ba ntse ba hlahisa tlhahiso ea lijo. Ho tsoa lipapisong tsena, rea tseba hore batho ba batenya haholo ba bonts'a ts'ebetso e kholo tseleng ea mesolimbocortical ho feta batho ba boima ba tloaelehileng ().

Mofuta o mong oa neuroimaging o sebelisa phapang ea setso sa positron emission tomography (PET) ho khetholla tšebetso ea dopaminergic le dopamine receptors. Mohlala, phuputsong e 'ngoe e sebelisang theknoloji ena, bafuputsi ba bontšitse hore dopamine e lokolla ho tsamaellana le litekanyetso tsa thabo e fumanoeng nakong ea ts'ebeliso ea lijo (). Phuputso e 'ngoe e fumane hore ha lithuto li hlahisoa ka mekhoa ea lijo, keketseho ea dopamine e ne e hokahana le boemo ba lithuto tse boletsoeng (). Boithuto ba mofuta ona bo tiisa hore ho na le maemo a tlase a li-receptor tsa dopamine maemong a bakuli ba batenya, hoo boholo ba phokotso bo lekanang le keketseho ea BMI (; ). Ho bona sena ho ka supa phokotso ea likarolo tse natefisang tsa ho ja lijo tse ngata, tse ka lebisang ho tšelisong e kholo ea puseletso. Phokotso ea li-receptor tsa dopamine e boetse e amana le ho fokotseha hoa ts'ebetso ea cortex ea pele, e ka bonts'ang phokotso ea boitšoaro mabapi le takatso ea lijo bakeng sa batho ba batenya haholo ().

Neuroimaging e boetse e pepesitse ho ata ha tšebetso ea neural lipakeng tsa botenya le bokhoba ba lithethefatsi, e leng ho ferekanyang maikutlo a hore ho lemalla lijo ho ka ba le karolo ho holiseng botena. Phetoho ena e makatsang ha e makatse, kaha lintho tse ngata tse tloaelo e hlekefetsoang li sebetsa tseleng tse dopaminergic ka tsela e ts'oanang le lijo tse fumanehang habonolo. Phallo e atileng methating ea ts'ebetso ea dopaminergic pathways e boetse e bontšitsoe pakeng tsa nts'etsopele ea botenya le bokhoba ba ho tsuba (), cocaine, heroin, joala le methamphetamine. Lintho tsena kaofela li sitisa ts'ebetso ea li-receptor tsa dopamine le ho fokotsa palo ea dopamine e lokolotsoeng ho batho ba lemaletseng (lithethefatsi).; ; ). Ho khahlisang, batho ba batenya haholo ha ba na monyetla oa ho sebelisa lithethefatsi tse seng molaong ho feta batho ba boima ba boima), mme ha ba etsa joalo, ba kotsing e fokolang ea ho ba le bothata ba tšebeliso ea lithethefatsi nakong e tlang (). Liphumano tsena li ka bonts'a hore batho ba batenya haholo ba fumana moputso o sebelisoang ke batho ba bangata ba sebelisang lithethefatsi.

Bopaki ba lefutso bakeng sa likamano lipakeng tsa botenya le moputso oa Dopaminergic Moputso

Ho na le bopaki bo bokellanang ba ho tšehetsa likamano lipakeng tsa botona le botšehali ba dopamine receptor, liphatsa tsa lefutso tsa dopamine, le liphatsa tsa lefutso tse kenyang tlhekefetso ea dopamine. Liphetoho ho efe kapa efe ea liphatsa tsena tsa lefutso li ka fetola maemo a ho hlasimolla ha dopaminergic bokong (Lethathamo 1).

Lethathamo 1  

Bopaki ba Neurogenetic bakeng sa Kamano lipakeng tsa Botenya le Dopamine.

Dopamine Receptor gen

Mefuta ea dopamine receptor e amehang ka ho fetelletseng ho botenya ke dopamine receptor D2 (DRD2), dopamine receptor D3 (DRD3), le dopamine receptor D4 (DRD4). Li-receptor tsena kaofela li na le libaka tse supileng tsa transmembrane 'me ke li-receptor tse kopantsoeng le G-protein. Li-receptor tsena tse tharo li boetse li khethiloe e le li-receptor tse kang D2, ho bolelang hore li thibela intracellular cyclic adenosine monophosphate (cAMP) ho hatella tsela eo e saenneng ().

DRD2

Li-receptor tsa D2 ke mofuta o fumanehang ka ho fetisisa oa dopamine receptor bokong (). Almale e fokolang ea A1 bakeng sa polymorphism e sebetsang (rs1800497, Taq1A) ea DRD2 e kopantsoe le phokotso e akaretsang ea palo ea li-receptor tsa D2 bokong (). Polymorphism ena e amahanngoa le "phello ea khaello ea moputso" e hlahisoang e le tlhekefetso e mengata kapa e nang le kotsi e mengata ho ba se nang ts'ebetso ea dopamine e nepahetseng.). Lintlha tsa Neuroimaging li netefalitse phokotso ea ts'ebetso ea moputso bakeng sa batho ba nang le genotype ena (), hape, joalo ka ha ho boletsoe pejana, boholo ba phokotso ea li-receptor tsa D2 bo lekana le keketseho ea BMI ho batho ba batenya ba nang le A1 allele (). Ntle le moo, allele e nyane e amana le karolo e eketsehang ea mafura a mmele ().

Ho theoha DRD2 gene ka li-kilobases tsa 17 tse batlang li le haufi, sebaka se seng sa polymorphic se bitsoang C957 T (rs6277) le sona se ama ts'ebetso ea dopamine receptor. The T allele (vs. C) e amana le maemo a fokotsehileng a DRD2 mRNA ka kakaretso hape le phetolelo e fokotseng ea mRNA eo ho proteni ea receptor (). Li-scens tsa PET li netefalitse hore phokotso ena e baka maemo a tlase a li-receptor tsa D2 maemong a batho ba nang le allele ena, le li-receptors tse teng li bonts'a botsitso bo tlase ba dopamine (). Ha allele ena e kopantsoe le tšusumetso ea allele ea Taq1A le lilemo, e hlalosa 40% ea phapang lipalo tsa li-receptor tsa D2 ho pholletsa le boko.

63 e 'ngoe e theoha gene, rs12364283 e sebakeng se bolokehileng sa khatello (). Ha ho makatse hore ha sebaka sena se khathatsoa ke phetoho ho T allele e nyane, sephetho se eketseha ka mongolo o mongata le bothata ba "receptor". Pono ena e khahla haholo, kaha e ts'ehetsa liphetho. Ho akaretsa thuto eo, liphetoho tsa polelo ea RNA mefuteng e mehlano e amanang le secretion ea dopamine li ne li amana (p = .0004) e nang le phaello e boima ho 6 ea likhoeli tse fetang phetiso ea liphio. Ho ipapisitsoe le likarolo tsena tse peli tsa bopaki, hoa utloahala ho bolela hore liphetoho tse bonoang ho RNA li ka hlahisoa ka ho fapana libakeng tsa bolaoli ba DNA bakeng sa mefuta eo.

DRD3

Ser9Gly polymorphism (rs6280) e sebetsang, e fumanehang ka har'a mofuta oa DRD3 letsohong le lelelele la Chromosome 3, e amahantsoe le ho eketseha ha dopamine. Ka ho khetheha, glycine allele e etsa hore dopamine receptor e be le tumellano bakeng sa dopamine e ntseng e eketseha 5-fold ha e bapisoa le ser allele (). Heterozygosity ea polymorphism ena e amahanngoa le lintlha tse phahameng ho impulsiveness (). Hantle feela, glycine allele e amahantsoe le ho tsuba (), tlhekefetso ea koae (), le schizophrenia ().

DRD4

Mofuta oa dopamine receptor 4 gene ke mofuta o batlang o le khutšoane (hoo e ka bang lipakeng tsa 3,400 base), mme ho fapana ho hoholo ho gene ena ho ka ts'oaroa ka 48-base-joala ea palo e fapaneng ea tandem (VNTR) ho Exon 3. VNTR ena e ka ba le lipakeng tsa 2 le 11 tse phetang karolo ena ea 48-base-pair. Alleles e boleloa ke palo ea likarolo tse phetoang. Ka tloaelo, allele e pheta-pheta ea 7 e thehoa joalo ka kotsi ea ho ba le mathata a mangata a fapaneng, ho kenyelletsa tlhokomelo-deficit / hyperactivity disorder le schizophrenia. Ho bana ba sekolo sa mathomo, bakuli ba 7-repe allele ba ne ba ja mafura a mangata le protheine ho feta ba neng ba e-na le bolelele bo fapaneng ba ho pheta (), ho fana ka maikutlo a hore mofuta oa lijo tse ratoang o ka itšetleha ka dopaminergic genotype.

Liphuputso tsa in vitro li bonts'itse hore haelese sa 7-pheta-tlama se tlamella ka tlase ho dopamine ka lebaka la liphetoho tse bang teng mosebetsing oa cAMP (). The alNXX-repeat allele e fokotsa haholo maemo a CAMP; leha ho le joalo, allelele e 'ngoe, e leng 7-pheta allele, e batla e sebetsa ho phokotso ena. ba khothalelitse hore, ka lebaka la ho iphetola hoa lintho tse tšoanang le ho fetoha ha lintho tse phelang, mefuta ea phetisetso ea 2- le 7 e lokela ho hlophisoa hammoho e le li-kotsi. Bangoli bana ba fumane phapang e kholo litekanyetsong tsa bo-ralitaba ba batlang bo-ralitaba ha li-group tsena li ne li hlophisitsoe ka tsela ena ho fapana le ho bapisoa ka nako e telele ha li bapisoa le nako e telele.

Dopamine Transporter Gene

Batsamaisi ba li-Neurotransmitter ke li-portal tsa membrane ea lisele tse ntšang li-neurotransmitters ho tloha synching le ho laola matla le nako ea li-neurotransmission. Tabeng ea dopamine, ho na le transporter e le 'ngoe feela, transporter e sebetsang ea dopamine, lelapa la sephethephethe sa solute 6 (transcorter ea neurotransmitter), setho 3 (SLC6A3). Mofuta o tšoanang o boetse o bitsoa DAT1.

Karolong ea 3 ′ e sa reroang SLC6A3 / DAT1, ho na le VNTR e amang hantle tlhatlhobo ea dopamine ho tsoa ho synapse. ba khothalelitse hore phetolelo ena ea VNTR e fetole mRNA liprotheine. Leha ho le joalo, bopaki mabapi le se boleloang ke phapang e 'ngoe le e ngoe bo kopantsoe. Ho bonts'itsoe hore alamo e pheta-pheto tse robong e eketsa mongolo oa SLC6A3 / DAT1, e lebisang ho baeti ba bangata. Ka lebaka leo, dopamine e eketsehileng e ntlafatsoa hape ke li-neurone tsa "presynaptic neurons" 'me ho na le dopamine e fokolang e fumanehang ho li-postynaptic neurons (). Leha ho le joalo, bafuputsi ba bang ba bontšitse hore lithuto tse nang le 9-repeat allele li na le palo e tlase ea baetsi ba dopamine ha ba bapisoa le ba nang le 10-repe allele ().

Dopamine Degradation gen

Mefuta e meng ea bohlokoa ea dopaminergic e amanang le moputso e kenyelletsa catechol-o-methyltransferase (COMT) le li-monoamine oxidase li-isomers A le B (MAOA 'me MAOB). Likhoutu tsena tsa liphatsa tsa lefutso tsa li-enzyme tse tlohelang dopamine, hammoho le ho khutlisetsa methapo ea methapo ea kutlo, li fokotsa palo ea dopamine e fumanehang mokokotlong oa synaptic. Ha mekhoa ena ea ho senya e fetoloa, maemo a dopamine a teng a ka eketseha kapa a fokotseha.

COMT

Catechol-o-methyltransferase e amahanngoa le moputso ka tšusumetso ea eona ea ho fumaneha ha dopamine ka cortex. Ke eona feela enzyme e ka sebetsang ho methylate synaptic dopamine mme e qala ts'ebetso ea ho phatloha. Mofuta o kopaneng oa sebaka se tloaelehileng sa polymorphic (Val108 / 158Met, rs4680) ho mofuta oa COMT se etsa hore enzyme ena e fokotse tšebetso (). Ka lebaka leo, batho ba nang le allele ena ba ka batla liphihlelo tsa ho etsa moputso “holimo.” Ho fanoa ka polymorphism e le lets'oao, le sepheo sa lithethefatsi, ho lemalla (). Ntle le moo, rs4680 met allele e amana le ho eketseha hoa botenya ka mpeng ho banna (). Empa, e fumane keketseho ea tšebeliso ea lijo tse nang le mafura a mangata le tsoekere e ngata ho ba nang le allel.

Hoo e ka bang li-kilobases tsa 64 hole le rs4680 ke mofuta o tšoanang oa G / C, rs4818 (Leu136Leu). Le ha ho se na phetoho e sebetsang liprotheineng e hlahisitsoeng ho tsoa ho mofuta ona, C allele ea polymorphism ena e amanang le BMI e eketsehang (). Ho bonahala monyetla oa hore polymorphism ena e sebetsa e le letšoao ho khokahano ea likokoana-hloko tsa mofuta o mong oa mofuta oa ho ferekana, mohlomong rs4818 e boletsoeng pejana.

MAOA

Monoamine oxidase A ke enzyme e etsang hore dopamine e fetole bioavailability e akaretsang ea neurotransmitter. Eena le molekane oa eona MAOB ba fumanehile ka mitochondria ea li-neuron mme ba senya dopamine e seng e tlositsoe ho synaptic cleft. VNTR ea 30-base-pair ea MAOA isoform ea mofuta ona e sebakeng sa papatso (). Karolo e ntlafatsang ea mofuta oa liphatsa tsa lefutso ke moo ho kenngoeng liprotheine tse tsoang teng hangata, kahoo li-polymorphisms sebakeng sena li na le tšusumetso e kholo ho fumaneheng ha lihlahisoa tsa gene. Tabeng ea VNTR ena, ho phetoa mantsoe a qotsitsoeng ho 2 ho 5 a tlalehiloe. Mabaka a tloaelehileng ka ho fetisisa ke maele a pheta-phetang a 3-, 3.5-, le 4, leha ho na le phapang maqhubu kahare ho merabe e meng le ea merabe (). Batho ka bomong ba nang le 3.5- le 4-pheta-alleles ba bonts'a tlhahiso e kholo ea mRNA ho feta ba nang le li-ling tse ling (), mme bashanyana ba pheta-phetoang ba na le khetho e kholo ea lijo tse nang le mafura a mangata le tsoekere ho feta tse phetoang tse khutšoane.). Ho ekelletsa moo, litlatsetso tse khuts'oane li ho fetisetsoa maloetse a tšoaetsanoang malapeng a motenya.).

MAOB

The allele of a single nucleotide polymorphism (SNP) ho MAOB isoform ea mofuta ona (B-SNP13, rs1799836) e lumellana le maemo a holimo a dopamine bokong (). Le ha ho le bohlokoa ho hlokomela hore MAOA le MAOB li na le phapano e fapaneng lihlopheng, li na le ts'ebetso e ts'oanang ea ho senyeha ha dopamine. Ho eketsa tšebetso ho isoform e le 'ngoe ho ka etsa phello ea mosebetsi o fokotsehileng ho o mong (). Ts'ebetso ea li-enzyme ka bobeli e lokela ho tsotelloa. Leha ho le joalo, lisele tsa adipose tse nkiloeng lithutong tse tebileng haholo li na le maemo a tlase a polelo bakeng sa mefuta ka bobeli ea li-oxidase ho feta lisele tse nkiloeng lithutong tse se nang 'nete (), kahoo ho "otla habeli" ho bobeli ba MAOA le MAOB ho ka ba le litlamorao tse kholo ho boima ba mmele ka tsela e tlatsetsang. e fumane palo e phahameng haholo ea genotypes e sebetsang ka tlase ho feta ha e bapisoa le lithuto tseo e seng tsa semmuso, leha polosorphism ea MAOB e sa amane haholo le boima kapa BMI ka boyona.

Mohlala oa Conceptual

Ka kakaretso, ho na le bopaki bo matla ba liteko bakeng sa kamano pakeng tsa liphatsa tsa lefutso tse amanang le dopamine le liphetoho tsa boima. Bopaki bona bo bontša hore mokhatlo o etsahala libakeng tse ngata litseleng tsa tlhahiso ea dopamine mme o supa hore liphetoho tse boima li ka tsamaisoa ka liphatsa tsa lefutso ho efe kapa efe ea lintlha tsena. Ntle le moo, tlhaiso-leseling ena e kena 'meleng o moholo oa tsebo mabapi le ho nona haholo, e leng lintho tse kang lilemo, morabe, bong, ts'ebetso ea' mele, ho ja lijo tse matlafatsang, le meriana le tsona li ka tlatsetsa ho matlafalo e eketsehileng. Re kopantse lintlha tsa lefutso le lintlha tsa boipaballo le boits'oaro / tikoloho ho theha mohlala o hlakileng oa nts'etsopele ea botena, joalo ka ha ho bonts'itsoe ho Setšoantšo sa 1.

Setšoantšo sa 1  

Mohlala oa 'nete oa boima ba' mele o lebisang botenya. Libui tse arolang lintho tse lebisang bothateng li entsoe ka mela e robehileng ho bonts'a tšebelisano lipakeng tsa bona, e ts'oanang le mohlala o hlahisitsoeng ke . Re ...

Ka lehlakoreng le letona la wheel, ho bonts'oa likarolo tsa tikoloho tsa ts'ebetso ea 'mele, lijo le meriana. Ehlile, keketseho ea ts'ebetso ea 'mele le lijo tse matlafatsang li fokotsa boima ba' mele le kotsi ea li-comorbidities tse atisang ho amahanngoa le botenya ho batho ba bangata (bakeng sa tlhahlobo e ntle, bona. ). Le ha e sa hlakisoe ka ho hlaka ke mohlala ona, genotype (le polelo ea mofuta oo) li ka susumetsa karabelo e ikhethileng ea motho mabapi le liphetoho phetoho ea 'mele le lijo. Mohlala, polelo ea melanocortin 4 receptor (MC4R) e amana le phetoho ea boima ba 'mele () hape e na le mofuta oa genotype o amanang le ts'ebetso ea mmele (). Le ha lipatlisiso li senotse mekhatlo e meng e tšepisang liphatsa tsa lefutso mabapi le likarabo tsa batho ba bang mabapi le liphetoho mesebetsing ea 'mele le lijo, boholo ba bona bo bile le litlamorao tse fokolang, mme lerata la mofuta ona la data le boetse le fokotsa ts'episo ea bona ka nako ena. Ntle le moo, bafuputsi ba sa tsoa qala ho utloisisa litsela tsa biochemical tse susumetsoang ke tse ling tsa likamano tsa mofuta ona. Ho sa tsotelehe, ho ikoetlisa le ho ja ho lula e le lintlha tsa bohlokoa tseo u lokelang ho nahana ka tsona bakeng sa boima ba 'mele bo lebisang ho botenya.

Meriana e meng e ka ba le litlamorao tse amanang le liphetoho tsa boima. Mohlala, meriana e meng bakeng sa khaello ea ho fokola ha kelello e amanang le phetoho ea boima ba 'mele e amanang le phetoho ea boima ba mmele (). Ho sebelisana pakeng tsa meriana le hona ho ka holisa litlamorao tse amanang le boima ba 'mele. Le ha ho sa bontšoe mohlala, liphatsa tsa lefutso li bapala karolo ea karabelo ea motho kalafong. Lekala la drugacogenomics le supa tšepiso e kholo ea ho sibolla le ho fokotsa litlamorao tsa tse ling tsa mekhatlo ena, empa hajoale, meriana e ntse e le tšusumetso ho holiseng kholo ea boima bo lebisang ho nona.

Mofuta, bong le lilemo li boetse li susumetsa ho nona. Maikutlo a setso ka botle a ka susumetsa karohano ea morabe kotsing ea ho nona, empa phapang lipakeng tsa merabe le eona e bohlokoa. Mohlala, mabapi le SNPs, merabe e fapaneng e sentse maqhubu a manyane-allele bakeng sa mefuta e fapaneng e amanang le botenya. Ho skeha hona ho ka etsa hore merabe e meng e be matla kapa e be le boima ba 'mele. Bong bo bapala karolo ea phepelo ea boima bo fumanoeng (ke hore, karolelano ea boima ba mmele le gynoid), eo ka nako eo e ka bakang kotsi ea li-comorbidities tse amanang. Mme qetellong, lithuto tse kholo tsa lefu la seoa li bontšitse hore batho ba tloaetse ho fumana boima ha ba ntse ba tsofala, ka ho hola ka boima ba 'mele lilemong tse mahareng tse bohareng (). Kahoo, lintlha tsa morabe, bong le lilemo li ke ke tsa hlokomolohuoa ha u nahana ka botenya.

Lebokose le ka ho le letšehali la mohlala le supa liphallelo tsa liphatsa tsa lefutso ho botho le karolo ea boko ea moputso, e leng se susumetsang ho nona le ho nona haholo, joalo ka ha re se re buile sehloohong sena. Re ile ra khetha mefuta ena ka lebaka la litloaelano tse nang le boima ba 'mele kapa botenya bo neng bo tlalehiloe ka har'a lingoliloeng, joalo ka ha ho kile ha buuoa pele. Phapang ea genotype bakeng sa liphatsa tsena tsa lefutso e ka hlalosa ho feto-fetoha ha motho ka mong ka lebaka la ho ba le boima ba 'mele. Mofuta o mong le o mong o hlahisitsoeng o na le li-polymorphisms tse susumetsang maemo a dopamine bokong ka ho ama bioavailability ka kakaretso ea neurotransmitter, ho fetola lipehelo tsa dopamine, kapa ho laola li-receptor tsa dopamine. Joalokaha ho se ho boletsoe pejana, ho tlama ka dopamine libakeng tsa eona tse amohelang lijo ho etsa hore motho a natefeloe, 'me ho tlama hona ho ikarabella bakeng sa boiphihlelo bo monate bo bang teng ha motho a ja lijo tse monate haholo.). Ntle le moo, liphetoho lipakeng tsa mokhoa oa lipalangwang li ka baka liphetoho maemong a ho tlangoa, ho latela hore na dopamine e na le monyetla oa ho tsamaisoa ka har'a neuron ea postynaptic kapa e ntseng e khutlisetsoa ka har'a neuron ea presynaptic.

Moetso oa conceptual o na le bohlokoa ba kutloisiso ea botenya mme, haholo-holo, bakeng sa kalafo ea ho nona. Ka tsela eo, dopaminergic pathways e fetohile lipheo tsa meriana bakeng sa nts'etsopele ea meriana e khahlanong le botenya. Empa, joalo ka ha mohlala o bonts'a, lipatlisiso tsa nako e tlang mabapi le kalafo ea botenya li lokela ho sebetsana le lintlha tsa tikoloho le liphatsa tsa lefutso ho fana ka monyetla o moholo oa katleho ea nako e telele ea kalafo ea ho fokotsa boima ba 'mele.

lumela hore baa fokola

dithuso tsa ditjhelete

Sengoli se senotse ho amohela tšehetso e latelang ea lichelete bakeng sa lipatlisiso, bongoli, le / kapa phatlalatso ea sengoloa sena: Mosebetsi ona o tšehelitsoe ke NIH / NINR liphallelo 1F31NR013812 (PI: Stanfill, cosponsors: Hathaway and Conley; ke NIH / NINR fana ka T32 NR009759 (PI: Conley), le moputso oa Southern Nursing Research Society Dissertation (PI: Stanfill).

Mongolo o botlaaseng ba leqephe

Menehelo ea Mongoli

AGS e kentse letsoho mohopolong le moralo o kentse letsoho ho etseng phihlello, ho hlahlobeng le ho tolokang; mongolo o ngotsoeng o ile a ntlafatsa haholo taba e ngotsoeng ka letsoho; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala. YC e kentse letsoho mohopolo le moralo o kentse letsoho ho etseng phihlello, ho hlahlobisisa, le ho tolokang; o ile a ntlafatsa haholo taba e ngotsoeng ka letsoho; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala. AC e kentse letsoho mohopolo le moralo; e kentse letsoho ho fumana, ho sekaseka le ho toloka; o ile a ntlafatsa haholo taba e ngotsoeng ka letsoho; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala. CT e thusitse mohopolo le moralo; e kentse letsoho ho fumana, ho sekaseka le ho toloka; o ile a ntlafatsa haholo taba e ngotsoeng ka letsoho; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala. RH e kentse letsoho mohopolo le moralo o kentse letsoho ho etseng phihlello, ho hlahlobisiseng, le ho hlalosang; o ile a ntlafatsa haholo taba e ngotsoeng ka letsoho; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala. PC e kentse letsoho mohopolo le moralo; e kentse letsoho ho fumana, ho sekaseka le ho toloka; o ile a ntlafatsa haholo taba e ngotsoeng ka letsoho; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala. DH e kentse letsoho ho emeng le moahong; e kentse letsoho ho fumana, ho sekaseka le ho toloka; sengoloa se ntlafalitsoeng ka mokhoa o hlakileng; e fane ka tumello ea ho qetela; mme e lumela ho ikarabella bakeng sa likarolo tsohle tsa mosebetsi ho netefatsa ho tšepahala le ho nepahala.

 

Phatlalatso ea Likhohlano

Sengoli se phatlalalitse hore ha ho likhohlano tse ka bang teng mabapi le lipatlisiso, bongoli le / kapa phatlalatso ea sengoloa sena.

 

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