Tšoantšiso ea BXing ea D2 Receptor Specific Binding ka Boima le bo tloaelehileng Batho ba sebelisang PET le (N- [11C] methyl) benperidol (2013)

. Sengoloa se ngotsoeng; e fumaneha ho PMC 2014 Nov 1.

Synfall. 2013 Nov; 67 (11): 748-756.

E hatisitsoe Inthaneteng 2013 May 30. doi:  10.1002 / syn.21680

PMCID: PMC3778147

NIHMSID: NIHMS511440

inahaneloang

Liphuputso tse entsoeng pejana tsa PET li bonts'itse liphumano tse tsoakaneng mabapi le ho fumaneha ha dopamine D2 / D3, ho fumaneha ha motho a le motenya ka bongata. Li-radioligands tsa Nonspecific D2 / D3 ha li lumelle tekanyetso e arohaneng ea D2 receptor (D2R) le D3 receptor (D3R) subtypes ea lelapa la D2 receptor, e ka 'nang ea bapala likarolo tse fapaneng ka boits'oaro mme e ajoa ka mokhoa o fapaneng ho feta bokong bohle. Li-radioligand tsena li boetse li sitoa ke dopamine ea endo native, tlhaloso e ferekanyang ea phapang ea ho fumaneha ha li-receptor ka litekanyetso tse fapaneng tsa tokollo ea dopamine. Boithuto ba hona joale bo sebelisitse ho nahana ka PET ka radioligand ea D2R-sele (N-[11C] methyl) benperidol ([11C] NMB), e sa senyeheng ke dopamine ea endo native, ho hakanya D2R binding e itseng (BPND) le kamano ea eona ho index ea boima ba 'mele (BMI) le lilemo ho 15-boima ba mmele (bolela BMI = 22.6 kg / m2) le 15 feta (bolela BMI = 40.3 kg / m2) banna le basali. Lintho tse amanang le bokuli kapa ho sebelisa meriana e sitisang matšoao a dopamine li ile tsa behelloa ka thoko. Striatal D2R BPND e ne e baloa ho sebelisoa mokhoa oa Logan graphical o nang le cerebellum e le sebaka sa litšupiso. D2R BPND likhakanyo li ne li phahame haholo ka li-putamen le caudate tse amanang le li-nucleus accumubs, empa li ne li sa fapana pakeng tsa lihlopha tse boima le tse batenya haholo. Melao ea BMI ha e kopane le D2R BPND. Age e ne e amana hantle le putamen D2R BPND ka lihlopha tseo ka bobeli. Liphetho tsena li fana ka maikutlo a hore ho fetoloa ho ikhethileng ha D2R ha ho amehe pathogenesis ea botena ka sethethe mme e hatisa tlhokahalo ea lithuto tse eketsehileng tse lekolang kamano pakeng tsa D3R, dopamine reuptake, kapa endo native dopamine le ho nona haholo.

Keywords: dopamine, botenya, NMB

SELELEKELA

Ho nona ke bothata bo boholo ba bophelo bo botle lefats'eng 'me bo amana le mathata a tebileng a kalafo le litlamorao tsa moruo (). Ho nona ka bongata ho ka ba ka tsela e amanang le tšebeliso ea lithethefatsi kaha ka bobeli li amana le liphetoho tse tšoanang phetisong ea dopaminergic ka mefuta ea methapo ea methapo.). Lithuto tsa batho li bonts'a hore ts'ebeliso ea lithethefatsi e amana le ho fumaneha ha drietal D2 / D3 dopamine receptor, joalo ka ha ho lekiloe ho vivo e nang le PET imaging (; Volkow et al., 1996; ; ). Leha ho le joalo, kamano pakeng tsa botenya le tsamaiso ea dopaminergic ho batho e lula e sa hlaka ka lebaka la liphetho tse hananang lipakeng tsa lithuto tsa PET. Haholo, lihlopha tse 'maloa (; ; ) e fumane hore botenya bo amahanngoa le ho fokotseha ha nako e fumane keketseho ea ho fumaneha ha li-receptor D2 / D3.

Ho rarahana ha ho lekola matšoao a dopaminergic a tšoaeang ho ka tlatsetsa liphetho tse fapaneng lithutong tsa batho ba tloaelehileng le ba batenya haholo. Lithuto tsa imaging tsa PET le SPECT tsa D2 / D3 receptor fumaneha ho botenya li sebelisitse [11C] moralo oa leqhubu (; ), [18F] fallypride () le [123I] IBZM (). Li-radioligand tsena li na le meeli ea bohlokoa. Taba ea pele, li-radioligand tsena ha li khetholle pakeng tsa D2 (D2R) le D3 (D3R) li-receptor subtypes tsa lelapa la D2 dopamine receptor (; ; ). D2R le D3R li na le phapang e fapaneng, leha e batla e hasana, e aba hohle ho bokong ba motho () ka hona e ka ba le likarolo tse fapaneng tsa ts'ebetso boits'oarong bo amanang le moputso. Taba ea bobeli, tokollo ea maqhutsu a dopamine e fokotsa tlamo e khethehileng ea [11C] raclopride, [18F] fallypride, kapa [123I] IBZM (; ; ), e etsang hore li-radioligands li be molemo ho lekola tlhahiso ea li-dopamine tsa endo native empa phetolelo e makatsang ea ho fumaneha ha D2 / D3 receptor lithutong tse fetileng.

E ipapisitse le bopaki ba ho fokotseha ha "striatal D2R" le ho fokotsitse ho fumaneha ha li-receptor tsa D2 / D3.) le ho fokotsa ho fumaneha ha li-receptor tsa D2 / D3 ho batho ba batenya (; ; ), re fane ka maikutlo a hore tlamahano e ikhethileng ea D2R e tla fokotsoa ho feta tekano le monna le basali ba boima ba tloaelehileng. Re laile ka hloko bakeng sa lilemo mme re sa kenyetse ba nang le maemo a kelello le lefu la tsoekere a amanang le ho hlobaela ha dopaminergic (; ). Re sebelisitse radioligand (N-[11C] methyl) benperidol ([11C] NMB), e nang le thepa e ikhethang e amohelang li-receptor. NMB e feta linako tsa 200 ha e khetha D2R ho feta D3R (), hape e tobile ho D2R ka mefuta e meng ea li-receptor tsa boko (; , ; ). Ntle le moo, NMB ha e chechisehe ka ho lokolloa ha dopamine ea endo native (), e lumellang tlhahlobo ea D2R e itseng e tlamang e sa kenngoeng ke mahloriso a synaptic dopamine. Hlokomela hore NMB e ka ngolloa ka e ngoe 11C kapa 18F ntle le ho fetola sebopeho sa molek'hule ea D2 ligand (; ). Kahoo, [11C] NMB le [18F] NMB ha se li-analogane empa li na le lik'hemik'hale (ka hona li-pharmacologic), 'me li fapana feela ka ho ngolisoa ka lebitso 11C kapa 18F, ka ho latellana.

LISEBELISOA LE MEKHOA

barupeluoa ba

Boima bo leshome le metso e mehlano bo tloaelehileng (BMI 18.9 - 27.7 kg / m2; lilemo tsa 22.4 - lilemo tsa 39.9; Banna ba 4) le 15 obese (BMI 33.2 - 47 kg / m2; lilemo tsa 25.4 - lilemo tsa 40.9; Banna ba 3) banna le basali ba nkile karolo phuputsong ena (Lethathamo 1). Bohle ba neng ba nka karolo ba ile ba qeta tlhahlobo e phethahetseng ea bongaka, ho kenyelletsa nalane ea bongaka le tlhahlobo ea 'mele, liteko tsa mali tse tloaelehileng, hemoglobin A1C, le tlhahlobo ea mamello ea glucose ea molomo. Bao ba nang le nalane e ipoletseng ea lefu la tsoekere, A1C ≥ 6.5% (48 mmol / mol), kapa liphetho tsa OGTT tse bonts'itseng ho sitisa tsoekere e potlakileng ea mamello, mamello e tsitsitseng ea glucose, kapa lefu la tsoekere (≥ 200 mg / dl, ()) ba ne ba qheletsoe ka thoko. Barupeluoa ba ile ba boela ba hlahlojoa hore na maemo a methapo ea kelello le a kelello ke tlhahlobo ea methapo, tlhahlobo ea kelello (Phuputso e Itseng ea Clinical ea DSM-IV (SCID, ), Beck Depression Inventory (BDI-II, Beck et al., 1996), Wechsler Abxandated Scale of Intelligence (WASI, ), le Karolo ea A ea lethathamo la tlhahlobo ea matšoao a batho ba baholo ba AdHD Self-Report Scale Symbale (ASRS-v1.1, ). Batho ba fumanoeng ba na le psychosis ea bophelo bohle, bohlanya, ts'ebeliso ea lithethefatsi, khatello e kholo ea maikutlo, phobia sechabeng, mathata a ho ja le ho tšoha, parkinsonism, IQ <80 kapa ba na le bokuli ba kelello kapa lefu la kelello (mohlala, ts'ebeliso e mpe ea lithethefatsi, lefu la Parkinson, lefu la Tourette, stroke) e ka e ama ho hlalosoa ha data ha ea kenyelletsoa thutong. Batho ba tsubang, baimana kapa ba anyesang, e ne e le postmenopausal, ba noa meriana e ka susumetsang sephetho sa thuto joalo ka kalafo ea dopamine agonist kapa antagonist (mohlala, antipsychotic kapa metoclopramide) ha ba kenyeletsoe. Barupeluoa bohle ba saenetse tumello e nang le tsebo pele ba nka karolo phuputsong, e ileng ea amoheloa ke Ofisi ea Ts'ireletso ea Batho ea Univesithi ea Washington.

Lethathamo 1 

Litšobotsi tsa Barupeluoa

Boitokisetso ba Radiopharmaceutical

Synthet [11C] NMB ke mochine o ikhethileng oa mokhoa o phatlalalitsoeng (, ). [11C] CO2 e hlahisitsoe ka 14N (p, α)11Karabelo ho C University ea Washington JSW BC-16 / 8 cyclotron, 'me e fetoloa [11C] CH3Ke sebelisa GE PETtrace MeI MicroLab (). [11C] CH3'Na, benperidol le base li ne li futhumetse 90 ° C bakeng sa metsotso ea 10, le [11C] NMB e arotsoe ka tšebeliso ea karolo ea pele ea HPLC e fetotsoeng. Phetoho ea lithethefatsi e sebelisitse theknoloji e matla ea ho kenyelletsa letsoho ho fana ka [11C] NMB ho 10% ethanol ho Sodium Chloride bakeng sa ente, USP. Sehlahisoa se felisitsoe ka mokhoa o sa sebetseng (0.2 μm filter), mme se ne se na le bohloeki ba radiochemical ≥ 95% le ts'ebetso e ikhethang ≥ 1066 Ci / mmol (39 TBq / mmol).

Ho fumana PET

[11C] NMB (6.4 - 18.1 mCi) e ne e tsamaisoa ka methapo ho feta 20 s ka catheter ea polasetiki e kentsoeng mothapong oa letsoho. Bakeng sa sehlooho ka seng, <7.3 μg ea NMB e sa ngolisoang e ile ea entoa. Litekanyetso tsa PET li entsoe ka Siemens / CTI ECAT EXACT HR +, e nang le mehele e 32 ea lisebelisoa tsa semmuso tsa BGO mme e fumana likhae tse 63 ka nako e le 'ngoe tse nang le sebaka sa 2.4 mm le axial FOV ea 15.5 cm. Tse tharo li ka khutlisoa 68Mehloli ea thupa ea Ge e sebelisoa bakeng sa likhakanyo tsa phetisetso ho lekanya lintlha tsa ho fihlella ka bonngoe. Tharollo ea sepakapaka ea Transaxial le axial setsing sa selae ke 4.3 mm le 4.1 mm ka botlalo bolelele bo lekanang (FWHM) ka mokhoa oa 3D (). Lintlha tsa tlhahiso ea tlhahiso li ile tsa bokelloa ka mokhoa oa 3D bakeng sa lihora tsa 2 ka kakaretso ea liforeimi tsa 30: 3 @ 1 min, 4 @ 2 min, 3 @ 3 min, 20 @ 5 min. Sekhechana sa PET se ile sa hlophisoa bocha ka sefepi se bonojoang ka morao, 'me sa sebetsa ka mokhoa o hlakileng ha seretse se kopantsoeng le leqhubu la Nyquist.

Ho fumana MRI

Bohle ba neng ba nka karolo ba ile ba tekenoa ke MRI skrineng sa Nokia MAGNETOM Tim Trio 3T ba sebelisa tatellano ea 3-D MPRAGE (TR = 2400 ms, TE = 3.16 ms, flip angle = 8, 176 sagittally-based oriental, FOV = 256 mm; voxels = 1 × 1 × 1 mm).

Tlhahlobo e thehiloeng ho ROI

Bakeng sa morupeluoa e mong le e mong, liforeimi tse matla tsa setšoantšo sa PET li ne li ngolisitsoe hammoho ho setšoantšo sa monka karolo sa MPRAGE joalokaha ho hlalositsoe (). Lintlha tse hlalositsoeng ke MRI le data ea PET li ile tsa hlahisoa hape sebakeng sa Talairach atlas ho (2 mm)3 ().

Libaka tse tharo tsa phaello ea linaha tse peli tsa phaello (ROI) (putamen, caudate le nucleus accumbens) le cerebellum (sebaka sa litšupiso) li fumanoe ho MPRAGE e 'ngoe le e' ngoe ea karolo e sebelisang FreeSurfer (e fumanehang ho http://surfer.nmr.mgh.harvard.edu). Ho fokotsa litlamorao tsa bophahamo ba likarolo, libaka tsa putamen le tsa caudate li ile tsa ntlafatsoa ke voxel e le 'ngoe e sebelisang sefahleho sa sefahleho sa gaussian se kopantsoeng le ho ts'oaroa, sa etsa hore 2 mm e fihle libakeng tsa libaka tsena (). Likhetla tsa nyutlelie li ne li se kholo hore li ka senyeha.

Li-ROI li ile tsa fallisoa ka setsing se le seng sa Talairach se tšoanang le litšoantšo tsa PET. Li-curve tse ntlafalitsoeng tse sebetsanang le ho bola li ile tsa ntšoa ho tsoa ho data ea PET e matla bakeng sa morupeluoa e mong le e mong. D2R e nang le bokhoni bo ikhethileng ba ho ba le matla (BPND) e ne e baloa bakeng sa ROI e 'ngoe le e' ngoe e sebelisang mokhoa oa graphan oa Logan ka ") joalo ka ha e ne e netefalitsoe pele ho [18F] NMB e nang le 3-compartment tracer kinetic model le mokhoa oa graphical o hlokang ho kenella ha arterial (; ). Mokhoa oa Logan o loketse tlhahlobo ena hobane cerebellum e na le tlamo e ikhethileng ea NMB lithutong tse phetseng hantle () 'me ha ho na monyetla oa hore lithuto tse nyarosang li hlahise libaka tse ikhethileng ka har'a cerebellum. Ntle le moo, le haeba ho na le liphapang tse teng sehlopheng sa batho ba batenya ho tlisoang ke [11C] NMB ka har'a cerebellum e joalo ka liphetoho phallong ea mali ea sebakeng seo, boteng ba mothapo oa mali, kapa ntho e sa lebelloang, mohopolo oa mantlha oa mokhoa oa ho bua oa Logan o nka hore liphetoho tsena, tse ts'oanang le ho sa tlangoa ho itseng, le tsona li etsahala ho shebisa ROI bakeng sa sehlopha seo sa thuto kapa motho a le mong. Kahoo BP e baliloengND e nka phapang ena. Lithaba li fumanoe libakeng tsa polane ea Logan bakeng sa data e fumanoeng 60-120 min kamora [11C] ente ea NMB. BPNDHo ile ha etsoa karolelano ea li-caudate tsa letsohong le letšehali le ka ho le letona, li-putamen le li-nucleus tse bokellaneng ho fokotsa papiso ea tikoloho le hobane ha ho na bopaki bo supang hore liphetho tsena li tla lekana.

Tlhahlobo e thehiloeng ho Voxel

Tlhahlobo e thehiloeng ho voxel e etselitsoe ho bona phapang e ka bang teng ho D2R e tlamahanyang pakeng tsa lihlopha tse boima le tse tloaelehileng tse neng li sa fumanoe ka tlhahlobo e thehiloeng ho ROI joaloka ho (). Software e fumanehang ka bolokolohi ea PVEOUT (https://nru.dk/pveout/index.php) le litšoantšo tse ngolisitsoeng ka kopanelo tsa MR bakeng sa thuto e 'ngoe le e' ngoe li ile tsa sebelisoa ho lokisa sephetho sa bophahamo ba molumo (PVE) ba sebelisa mokhoa o phatlalalitsoeng (; ). [11C] Litšoantšo tsa NMB PET tse lokisitsoeng bakeng sa PVE li ile tsa etsetsoa motho ka mong. BPND 'mapa oa voxel o ile oa etsoa bakeng sa thuto e' ngoe le e 'ngoe o sebelisa litšoantšo tsena' me oa bapisoa le lihlopha tse tloaelehileng tsa boima le ba motenya ka mokhoa oa voxel o sebelisang SPM8 (http://www.fil.ion.ucl.ac.uk/spm).

Lipatlisiso tsa sethathamo

Tloaelo ea kabo bakeng sa mefuta-futa e tsoelang pele e ile ea hlahlojoa ho sebelisoa liteko tsa D'Agostino le Pearson omnibus maemong a boima bo tloaelehileng le lihlopha tse nonneng ka ho khetheha. Morabe le kabo ea bong lipakeng tsa lihlopha tse boima bo tloaelehileng le tse nonneng li ile tsa lekoa ka liteko tsa Chi-square. Ho khetholla monyetla oa hore liphallelo tse fapaneng tsa morabe ka boima bo tloaelehileng le lihlopha tse nonneng li ka ama sephetho, litšobotsi tsa bankakarolo le BP ea pelehi.ND likhakanyo li ile tsa bapisoa lipakeng tsa lithuto tsa batho ba Caucasus le ba Maafrika a batenya ho tlola le tse pakeng tsa lithuto tsa Baithuti t-Test kapa univariate kakaretso linear (GLM) sebelisa lilemo e le covariate. BMI, lilemo, boemo ba thuto, BDI le ASRS Karolo ea A li ne li bapisoa pakeng tsa lihlopha le Liithuti tsa pakeng tsa lithuto tLiteko, kapa, maemong a kabo e sa tloaelehang, Mann-Whitney eo e seng ea maemo ULiteko. BPND likhakanyo tsa putamen, caudate le nucleus li ne li bapisoa pakeng tsa lihlopha tse nang le mehato e phetoang ea GLM e sebelisang lilemo e le covariate. Boitekong ba ho ikamahanya le li-ROI lithutong tse tšoanang (; ) re bapisa le BP e kopaneng ea stPND ROI (karolelano ea putamen le caudate BPND boleng) lipakeng tsa lihlopha tse nang le GLM e sa laoloeng ho laola lilemo. Kamano lipakeng tsa BMI, lilemo le D2R BPND li baliloe ho sebelisoa tsa Pearson r kapa Spearman rho bakeng sa ROI ka 'ngoe. Bakeng sa tlhahlobo ea SPM8 e thehiloeng ho voxel, lihlopha li ile tsa bapisoa le tsa Student t-e leka ho sebelisa lilemo e le covariate. Liphetho li ne li nkuoa e le tsa bohlokoa ho α ≤ 0.05.

Tlhahlobo ea matla

Matla a boithuto ba rona ba ho fumana liphapang ho D2R BPND likhakanyo lipakeng tsa boima bo tloaelehileng le ba batenya hammoho le ho fumana khokahano lipakeng tsa D2R BPND likhakanyo le BMI sehlopheng sa batho ba batenya haholo e ile ea baloa ho latela liphetho tse tsoang liphuputsong tse fetileng tsa ho fumaneha ha D2 / D3 receptor (; ; ) le ea rona re sebelisa G * Power 3, e fumanehang ho http://www.psycho.uni-duesseldorf.de/abteilungen/aap/gpower3 (). Phello ea boholo ba liphapang molemong oa ho fumaneha ha li-D2 / D3 receptor lipakeng tsa lihlopha tse sa bateng le tse batenya tse sebelisang [11C] moralo oa leqhubu () le [123I] IBZM () ho hakanngoa hore ke 1.35 le 1.13 (Cohen's d), ka ho latellana. Re nahana ka litlamorao tse tšoanang thutong ea rona, mohlala oa rona oa batho ba 15 ka sehlopha o ne o e-na le matla lipakeng tsa 0.85 le 0.95 ho fumana phapang ea boholo bona ba lipakeng tsa boima bo tloaelehileng le ba batenya. Khokahano lipakeng tsa striatal D2 / D3 receptor phumaneho le BMI sehlopheng sa botenya e ne e le −0.84 e sebelisa [11C] moralo oa leqhubu () le 0.5-0.6 sebelisa [18F] fallypride (). Boholo ba sampole ea rona bo ne bo na le matla a 0.5-0.97 ho fumana litla-morao tsena ho isa ho tse kholo.

LIPOTSO

Teko ea maemo

Mehato eohle e itšetlehileng ka mokhoa o sa feleng e bile le kabo e tloaelehileng lihlopheng ka bobeli (p ≥ 0.07 ea liteko tsohle) ntle le bakeng sa BDI (p = 0.01) le ASRS Karolo ea A (p <0.05) sehlopheng sa boima bo tloaelehileng le lilemo sehlopheng se nonneng (p = 0.05). Litaba tsena li ile tsa nkuoa joalo ka ha li sa tsamaisoe hangata lithutong tse latelang.

Libopeho tse nkang karolo le BP ea striatalND Likhakanyo ka bong le bong

Ho arolelanoa ka setso pakeng tsa boima bo tloaelehileng le ba batenya ho fapane haholo (χ2(2) = 6.2, p = 0.05, Lethathamo 1), ha karolelano ea bong e ne e sa (χ2(1) = 0.19, p = 0.67). BMI, lilemo, le lilemo tsa thuto li ne li sa fapana lipakeng tsa lithuto tsa Caucasian tse batala le tsa Maafrika a Amerika (p ≥ 0.2). Ha o laola lilemo, ntho e tsejoang ka mokhoa o fosahetseng oa ho kopanya le ho fumaneha ha dopamine receptor le ho tlama ho itseng.; ; ; ), BP e hlaselangND e ne e sa fapana lipakeng tsa Caucasus le Maamerika a Maafrika sehlopheng se batenya (p ≥ 0.14 ea lipapiso tsohle). Ho fumana le ho feta hore na phapang ea bong le morabe e ne e pata likamano pakeng tsa botona le BP ea thobalanoND. Basali ba Caucasian ba boima bo tloaelehileng ebile ba batenya ha baa fapana ka BP ea striatalND sebakeng leha e le sefe (p ≥ 0.19 ea tlhahlobo eohle). Ntle le moo, BMI ha ea ka ea lumellana le BPND bakeng sa sebaka leha e le sefe se boima ba 'mele (p ≥ 0.29, e laolang lilemo tse ngata kapa e feta (p ≥ 0.11, e laolang lilemo) Basali ba Caucasian. Ka hona, bong le morabe li ne li sa laoloe ho litlhahlobo tse ling kaofela.

Litšobotsi tsa karolo

Barupeluoa ba boima ba ho feta le ba tloaelehileng ba ne ba sa fapana ka lilemo (U28 = 78, p = 0.16), boemo ba thuto (t28 = -1.58, p = 0.13), BDI (U28 = 78, p = 0.16), WASI IQ (t28 = -1.82, p = 0.08), kapa ASRS Karolo A (U28 = 93.5, p = 0.44) lintlha.

[11C] NMB BPND

Lihlopheng tse nang le boima bo tloaelehileng le tse batenya li ne li sa tšoane ka D2R BP ka kakaretsoND likhakanyo (phello e kholo ea sehlopha, F1,27 = 0.12, p = 0.73; Feiga. 1A, C, Lethathamo 2). Joalokaha ho lebelletsoe (), ho bile le phello e kholo ea sebaka (F2,54 = 30.88, p <0.0001), moo putamen BPND likhakanyo li ne li phahame ho feta tsa caudate (p <0.05) le li-nucleus accumbens (p <0.0001). BP ea CaudateND likhakanyo li ne li boetse li phahame ho feta tsa li-nucleus accumbens (p <0.0001, Setšoantšo sa 1A). Ho ne ho se na tšebelisano lipakeng tsa sehlopha le sebaka (tšebelisano ea sehlopha sa × F2, 54 = 0.86, p = 0.43, Feiga. 1A, C). Li-striatal tse kopaneng li bolela BPND likhakanyo tsa ho fumaneha ha D2R li ne li sa fapana lipakeng tsa lihlopha tse boima bo tloaelehileng le ba batenya (F1,27 = 0.23, p = 0.63; Feiga. 1B, C, Lethathamo 2). The putamen le bolela striatal BPNDs bakeng sa bankakarolo ba motho a le mong o moholo e ne e le 2.42 le 2.24 tloaelo e khelohileng ka holimo ho moelelo, ka ho latellana. Ka hona, litlhahlobo tse hlalositsoeng kaholimo li ne li etsoa ntle le taba ena, 'me ka mokhoa o ts'oanang, li sa hlahise liphapang ho BP ea striatal BPND lipakeng tsa boima ba 'mele le tse batenya haholo (phello e kholo ea sehlopha, F1,26 = 0.05, p = 0.82 ea mehato e phetoang ea GLM; F1,26 = 0, p = 0.98 ea GLM univariate).

Setšoantšo sa 1 

Tlamo e khethehileng ea Striatal D2R ha e fapana lipakeng tsa batho ba batenya le ba boima bo tloaelehileng
Lethathamo 2 

BP ea StriatalND Ho hakanngoa

Tlhahlobo e thehiloeng ho Voxel

Ho ne ho se na liphapang pakeng tsa lihlopha ho D2R BPND kamora ho bapisa lipapatso tse ngata hore na moqapi a ka ba teng o kenyellelitsoe tlhahlobisong (p > 0.05 bakeng sa lihlopha tsohle).

[11C] NMB BPND ka mose BMI

BMI ha ea ka ea lumellana le D2R BPND Likhakanyo tsa ROI efe kapa efe ea striatal ROI kapa li-striatum tse kopaneng sehlopheng sa boima bo tloaelehileng (p ≥ 0.46) kapa sehlopha sa batenya (p ≥ 0.27; Feiga. 2, A-D, Lethathamo 3). Kantle ho motho ea ka bang teng kantle ho naha, caudate BPND e ne e amana hantle le BMI sehlopheng sa batho ba batenya haholo.r11 = 0.58, p <0.05, 95% karohano ea boits'epo, 0.08 ho 0.85) empa ho ne ho se na likamano tsa bohlokoa lipakeng tsa BMI le libaka tse ling tsa striatal (p ≥ 0.1).

Setšoantšo sa 2 

Tlamo e khethehileng ea Striatal D2R ha e amanang le BMI ho batho ba batenya kapa ba boima bo tloaelehileng
Lethathamo 3 

Pearson's Correlations e arohaneng (r) Pakeng tsa BMI le Striatal BPND, Taolo ea Bofuma

[11C] NMB BPND ho theosa le lilemo

Ho lithuto tsa boima bo tloaelehileng le tse batenya haholo, lilemo li ne li sa tsamaellane hantle le D2R BPND likhakanyo tsa putamen (p <0.05 bakeng sa khokahano ka 'ngoe) empa e se caudate, nucleus accumbens kapa striatum e kopaneng (p ≥ 0.09, Feiga. 3A-D, Lethathamo 4). Ntle le taba ea monko o monate o hlalosoang e le morekisi karolong e fetileng, lilemo ha li a lumellana haholo le BP ea striatalND sehlopheng sa botenyap ≥ 0.07).

Setšoantšo sa 3 

Tlamahano e khethehileng ea Striatal D2R e amahanngoa le lilemo ho batho ba tloaelehileng ba boima ba 'mele le ba batenya haholo
Lethathamo 4 

Likamano tsa Spearman (rho) Pakeng tsa Age le Striatal BPND

TŠOHLOA

Ha rea ​​fumana phapang ho tlama ho ikhethang tsa D2R, joalo ka ha ho hakanngoa ke [11C] NMB BPND, lipakeng tsa batho ba boima bo tloaelehileng le ba batenya haholo. Re sebelisitse radioligand e ikhethang ea PET [11C] NMB, kahoo litekanyetso tsena ha lia ka tsa ferekanngoa ke D3R e tlamang kapa ka tokollo ea dopamine ea endo native (; ). Ntle le moo, liphetho tsa rona ha lia ka tsa ferekanngoa ke maemo a amanang le a qheletsoeng ka thoko a ka amang likamano tse itseng tsa dopamine receptor, joalo ka lefu la tsoekere, bokuli ba methapo, kapa mafu a kelello le tlhekefetso ea lithethefatsi (, ).

Ha ho na monyetla oa hore re hlotsoe ho fumana phapang ho tlamaha e ikhethileng ea D2R lipakeng tsa li-boima bo tloaelehileng le tse batenya ka lebaka la sampole e sa lekaneng. Ho ipapisitsoe le liphetho tsa lithuto tse fetileng (; ; ), palo ea lithuto tse ngolisitsoeng thutong ea rona e fane ka matla a lekaneng ho lekana boholo bo boholo ho isa bo boholo lipapisong tsa sehlopha le bakeng sa khokahano ea D2R e ikopantseng le BMI. Re lokela ho hlokomela hore boholo ba sehlopha sa rona bo kholo ho feta kapa bo lekana le ba lithuto tse 'maloa tsa fetileng tsa D2 / D3 PET: n = 15 / sehlopha; : n = 8-14 / sehlopha; : n = 10 / sehlopha). Seo re se fumaneng se fana ka maikutlo a hore ha li-comorbidities tse loketseng li qheleloa ka thoko, ho tlama ha D2 e ikhethileng ha e ikarabelle bakeng sa liphapang tse bonoeng nakong e fetileng tsa D2 / D3 ho fumaneha ha botenya (; ; ; ). Lintlha tse ling tsa ho saena tsa dopamine li lokela ho hlahlojoa, joalo ka li-receptor tsa D3R, tlhahiso ea dopamine ea endo native, pheta-pheta ka dopamine transporter kapa tsamaiso ea len messengerosa la bobeli.

Khetho ea [11C] NMB bakeng sa D2R ea lelapa la D2 receptor le fetang D3R () e kanna ea hlalosa phapang lipakeng tsa liphetho tsa rona le lithuto tse fetileng. Li-radioligands tsa PET tse sebelisitsoeng lithutong tse fetileng tsa botenya joalo ka [11C] moralo oa leqhubu (; ) le [18F] fallypride () le mahlaseli a kotsi a SPECT [123I] IBZM () se ke oa khetholla hantle lipakeng tsa D2 le D3 subtypes (; ; ). Haeba D3R e tlamang e fetotsoe ho botenya, e ka hlalosa phapang pakeng tsa ho fumana ha rona le lithuto tse ling ka li-radioligands tse sa tobang tsa D2 / D3. D2R e etsahala ka lipalo tse phahameng maemong a phahameng a dorsal striatum, nucleus accumbens, exteriorriatal subcortical and cortical libakeng ha D3R e le teng maemong a phahameng maemong a phahameng (ka ho fapana le "lateral" caudate le putamen, khetla ea li-nucleus accumbens le likarolo tse ling tsa limbic () ka hona e ka bapala karolo e kholo mosebetsing oa moputso. Le ha D3R e hlakile e le sesosa sa ho batla lithethefatsi le ho lemalla lithethefatsi ho litoeba le litloholo tse seng tsa batho.) ka bopaki bo susumetsang ba batho (), ho na le bopaki bo tsoakiloeng le bo fokolang bakeng sa karolo ea striatal D3R ho litoeba () le motho (; ) botenya. Lintlha tse tsoang thutong ea rona le litlalehong tse fetileng li hatisa bohlokoa bo ka bang teng ba D3R boteng ba botona le tlhokeho ea lithuto tsa nako e tlang li sebelisa radioligand ea D3R-khetha PET.

Ho se khonehe ha li-radioligands tsa PET ka dopamine ea morao-rao le tsona li ka kenyelletsa phapang lipakeng tsa liphetho tsa rona le tsa lithuto tse fetileng. [11C] NMB ha e senyehe ke dopamine ea endo native (), empa [11C] raclopride, [18F] ka ntle ho naha le [123I] IBZM ke (; ; ). Kahoo, haeba botenya bo amahanngoa le dopamine ea dopamine e eketsehang ea striatal, ka lebaka la keketseho ea dopamine kapa ho ts'oaroa ho fokolang, joale [11C] lebala le marang-rang, [18F] fallypride, le [123I] lithuto tsa IBZM li kanna tsa fumana ho fumaneha ha li-receptor tsa D2 / D3 ho striatum, ka lebaka la ho fallisoa, ha [11C] NMB e hana. Liphetoho maemong a dopamine ea extracellular ho botenya li ithutile ka mokhoa o sa tobang bathong. Lintlha tse tsoang lithuto tsa fMRI tse entsoeng lithutong tsa batho li bonts'a ts'ebetso e kholo ho thusa mabapi le lijo cues (ka mantsoe a mang, litšoantšo tse fumanehang tsa lijo tse nang le khalori e ngata ho feta batho ba sa batleng haholo.), empa ts'ebetso e tsitsitseng ea ts'ebetso ha e araba tshebediso ya ea lijo tse fumanehang habonolo tse neng li kopantsoe hampe le BMI ho batho ba batenya haholo.). Ka hona, tlhaiso-leseling e tsoang lithutong tsa batho e bonts'a hore sistimi e matlafetse ho batho ba boima bo feteletseng le ba batenya ka lebaka la ts'usumetso ea lijo empa e le mafolofolo nakong ea ts'ebeliso ea lijo. Monyetla o moholo oa ho sebelisa [11C] NMB ho PET ho lekanya D2R ke hore ha e amehe ka liphetoho tsa nakoana ho mahloriso a synaptic dopamine. Leha ho le joalo, liphetoho tsena li ka sebetsa le botena. Fuoa hore ts'ebetso ea ts'ebetso ea striatal e matla haholo ebile e itšetlehile ka boits'oaro ba motho ka nako e telele (mohlala, karabelo lijong susumetsa ba bang khahlano le lijo kamohelo), lithuto tsa nako e tlang li hloka ho sebetsana le menyetla ena ka ho lekanya tlhahiso ea dopamine ea endo native tlasa maemo a fapaneng a satiety o sebelisa .ligands tse sitisoang ke endo native dopamine (mohlala [11C] lebala la marang-rang)] ..

Ntho e ka fokolisang thuto ena ke hore banna le basali ba merabe e mengata ba kenyellelitsoe e le lithuto. Ho ka etsahala hore ho fapana ka lebaka la lintlha tsena ho kanna ha ba le tšusumetso ea liphumano tse tlalehiloeng mona. Boithuto bona bo ne bo sa etselitsoe kapa ho fuoa matla ho bona hore na ho na le phapang e kholo ea lipalo maemong a ikhethang a tlatselletsang a D2R pakeng tsa banna le basali kapa pakeng tsa merabe e fapaneng. Leha ho le joalo, litekanyetso tse ikhethileng tsa D2R li ne li sa fapana pakeng tsa MaCaucasian le Maamerika a Maafrika sehlopheng sa botenya kapa lipakeng tsa basali ba Caucasian ba tloaelehileng le ba batenya. Phapang pakeng tsa botona le botšehali ha ea ka ea tlalehoa lithutong tse fetileng tsa PET tsa D2 / D3 receptor fumaneha ka botenya (; kapa ka e kholo [11C] Phuputso ea NMB PET ea banna le basali ba phetseng hantle (). Ka hona, ha ho na monyetla oa hore liphapang tsa morabe le bong li kentse letsoho ho seo re se fumaneng. .Kaholimo, ha ho na monyetla oa hore phapang lipakeng tsa thuto ea rona le ba bang ka litšobotsi tsa thuto (mohlala, BMI, thobalano, kapa lilemo) li hlalosa ho se tšoane ka liphetho. Phuputso ea rona e ne e reretsoe batho ba batenya haholo ba nang le BMI ea 30 - 50 kg / m2, ho etsa bonnete ba hore batho ka bomong ba lekana le maemo a botenya, empa hape ba ka qoba li-comorbidities tsa bophelo bo botle le lilemo mme ba ntse ba lekana ka har'a litheko tsa scanners (ka karolelano obese BMI = 40.3 kg / m2; mefuta = 33.2 - 47 kg / m2). Lithuto tse ling li lebisitse batho ba tšoanang le (: karolelano ea makhopho BMI = 40 kg / m2, bophara ha bo fumanehe) kapa BMI e tlase (: boima bo fetang / boima bo fetang BMI = 33 kg / m2, mefuta e sa fumanehe), empa thuto e le 'ngoe e ne e na le BMI e phahameng ebile e le karolo e fetang e le' ngoe feela: karolelano ea makhopho BMI = 46.8 kg / m2, mefuta = 38.7 - 61.3 kg / m2; : karolelano ea makhopho BMI = 51 kg / m2, bophara = 42-60 kg / m2). Phapang e teng tlamong e ikhethileng ea D2R e ka bonoa feela ho batho ba batenya haholo. Leha ho le joalo, litholoana tsa 'me e ka hanyetsa taba ena. Ho khahlisang, joalo ka empa ka lehlakoreng le leng ho fumanoe ho , caudate D2R tlama e ikhethileng e ne e tsamaellana hantle le BMI sehlopheng sa batho ba batenya ha ho laoloa lilemo le ho sa kenyeletse motho ea ka ba rekisang. Ho ka etsahala hore litekanyo tsa "dopamine" tse fokolitsoeng le ho eketseha ha BMI lithutong tse natefeloang li thusa ho eketsa D2R ho caudate joalo ka ha ho hlokometsoe ho .

Kamora nako, barupeluoa ba rona ba boima bo tloaelehileng le ba batenya e ne e le bonyenyane (bolelele bo tloaelehileng ba boima: 22.4 - lilemo tsa 39.9; feta: 25.4 - 40.9 lilemo ho feta ho (mefuta: 25-54 lilemo), (mefuta = 20 - lilemo tsa 60) le (bolele lilemo = 40 lilemo, bolelele ha bo fumanehe). Nako ea lilemo e tsamaisoa hampe le ho fumaneha ha D2 / D3 fumaneha joalo ka ha e lekantsoe ke [11C] lebala le marang-rang, [18F] ka ntle ho naha le [123I] IBZM (; ; ), hape le D2R e tlamang joalo ka ha e lekantsoe ke [11C] NMB (), e fumanoeng thupelong ea hajoale lihlopheng ka bobeli bakeng sa putamen. Ka lehlakoreng le leng, ha rea ​​fumana kamano e bohlokoa lipakeng tsa D2R e tlamang le lilemo bakeng sa libaka tse ling tsa striatal. Sena se ka etsahala ka lebaka la lilemo tse patisaneng tse ithutoang, tse khethiloeng ka boomo ho qhelela ka thoko botsofaling e le ntho e nyarosang ho BPND likhakanyo.

Seo re se fumaneng se fana ka leseli mabapi le karolo ea ts'oaetso ea dopaminergic ea boteng ka botenya ka ho bontša hore motheo oa tlamahano ea lelapa la D2 receptor subtype ea lelapa la D2 receptor ha le fapana lipakeng tsa batho ba baholo ba tloaelehileng le ba batenya. Kaha batho ba nang le lefu la tsoekere ba ne ba sa kenyelletsoa phuputsong ena, ho lula ho sa tsejoe hore na D2R e ka bapala karolo ea kopano pakeng tsa lefu la tsoekere le botenya. Ho hlokahala lithuto tse eketsehileng ho araba potso ena le ho utloisisa hamolemo tlatsetso ea phetisetso ea dopaminergic le D3R e tlamang ho supa dopaminergic ho supa boima bo tloaelehileng le ba batenya.

LINTLHA TSA LITLHAHO

Boithuto bona bo tšehelitsoe ke Setsi sa Naha sa Bophelo - NIDDK Grant R01 DK085575-03 (SAE, ECB, SAR, TH), T32 DA007261 (SAE, JVA-D., DMG), DK 37948, DK 56341 (Nutrition Obesity Research Center ), NS41509, NS075321, NS058714 le UL1 TR000448 (Clinical and Translational Science Award).

Bangoli ba leboha Heather M. Lugar, MA, Jerrel R. Rutlin, BA le Johanna M. Hartlein, MSN ka menehelo ea bona thutong.

Mongolo o botlaaseng ba leqephe

 

Bangoli ba tlaleha hore ha ho lintoa tse thahasellisang.

 

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