CRF-CRF1 Receptor System ea Central and Basolateral Nuclei ea Amygdala e fapana ka ho fapana le ho ja lijo tse nang le phepo (2013)

. 2013 Nov; 38 (12): 2456-2466.

E hatisitsoe Inthaneteng 2013 Jul 10. E hatisitsoe 2013 Jun 10 e hatisitsoeng. doi:  10.1038 / npp.2013.147

PMCID: PMC3799065

inahaneloang

Lijo tse matla haholo le ho ja lijo ke lintho tse ka sehloohong tse tlatsetsang bakeng sa nts'etsopele ea ho ja lijo tse feteletseng ka botenya le mathata a ho ja. Re kile ra bonts'a hore ho fihlella ka hare ho lihlahisoa tsa lijo tse hlahisang corticotropin-releasing factor-1 (CRF1) mekhoa e amohelehang ea mohanyetsi, e akarelletsang ho ja lijo tse ngata haholo, hypophagia ea khauta e tloaelehileng, le boitšoaro bo kang bo tšoenyehileng. Leha ho le joalo, libaka tsa boko lipakeng tsa liphello tsena ha li tsejoe. Lipoe tsa banna ba Wistar li ne li feptjoa chow ka ho tsoelang pele bakeng sa matsatsi a 7 / beke (Chow / Chow sehlopha), kapa ho fepa ka matsatsi a mabeli a 5 / beke, ho lateloa ke sucrose, lijo tse monate tsa matsatsi a 2 / beke (Chow / e khoneha sehlopha). Ho latela mekhoa e sa foleng ea lijo, liphello tsa microinfusing CRF1 R121919 (0, 0.5, 1.5 μg / lehlakoreng) karolong e bohareng ea amygdala (CeA), nucleus ea basolateral ea amygdala (BlA), kapa sebaka sa bethe sa stria terminalis (BNST) li ile tsa hlahlojoa ka ho ja haholo ea lijo tse monate, ho tsuba hypophagia, le boitšoaro bo kang ba boitšoaro. Ho feta moo, CRF immunostaining e ile ea hlahlojoa bokong ba ho ja likhoto tse tsamaeang ka maoto. Intra-CeA R121919 e thibeletse ho ja lijo tse ngata haholo le ho tšoenyeha ho Chow / e khoneha likhoho, ntle le ho ama chow hypophagia. Ka lehlakoreng le leng, intra-BlA R121919 e fokolitse phetoho ea ho kena Chow / e khoneha likhoho, ntle le ho ba le tšusumetso e kang ea boitšoaro. Intra-BNST kalafo ha e na phello. Litšebeletso tsa phekolo ha lia fetola boitšoaro ba Chow / Chow likhoto. Immunohistochemistry e senole palo e ntseng e eketseha ea lisele tsa CRF tse ntle ho CeA-empa eseng BlA kapa BNST-of Chow / e khoneha likhoto, nakong ea ho tlohela ka bobeli le ho nchafatsoa ha lijo tse monate, ha li bapisoa le lithibelo. Liphetho tsena li fana ka bopaki bo sebetsang ba CRF-CRF1 mokhoa oa ho amohela li-CeA le BlA o na le phapang pakeng tsa mekhoa e mebe ea phepo ea likoloi.

Keywords: motsoako oa corticotropin-release, BNST, ho lemala, ho tšoenyeha, hypophagia, rat

SELELEKELA

Lijo tse phahameng haholo (mohlala, lijo tse nang le tsoekere le / kapa mafura) li lumeloa hore ke tsona tse ka sehloohong tse tlatsetsang ho hlahelang ho qobella ho ja lijo ka mefuta e itseng ea botenya le mathata a ho ja (; ). Litemana tse ngata li teng pakeng tsa ho lemalla lithethefatsi le ho ja lijo tse ngata tse khahlisang haholo, ho kenyeletsa ho lahleheloa ke taolo ea lithethefatsi / lijo, ho se khone ho khaotsa ho sebelisa / ho ja lijo ho sa tsotellehe liphello tse mpe, mahlomola le dysphoria ha u leka ho ikhutsa lithethefatsi / lijo (; ). Tsena matšoao a tloaelehileng a 'nile a etsoa hore a hlahe ho tsoa ho se nang likotsi tsa lipotoloho tsa boko, tse kenang ho lemalla lithethefatsi le ho ja lijo tse qobelloang.

Mofuta oa mofuta oa corticotropin-1 (CRF1) Batho ba loantšanang le batho ba amohelitsoeng ba 'nile ba etsoa hore e be litlhaselo tsa morao-rao tse bakoang ke mathata a ho lemalla motho ka lebaka la matla a bona a ho fokotsa liphello tse susumelletsang ho tlosoa (). CRF ke mohokahanyi oa bohlokoa oa endocrine, kutloelo-bohloko, le boitšoaro ba likarabo tsa khatello ea kelello (; ). CRF mokokotlong oa phallo ea hypothalamus e laola karabo ea hypothalamic-pituitary-adrenal (HPA) khatellong ea maikutlo, empa liphello tsa boitšoaro tsa CRF ke tsa HPA tse ikemetseng ebile li kopanngoa ke libaka tsa bokooa tsa extrahypothalamic (). CRF-CRF ea extrahypothalamic1 mokhoa oa ho amohela likokoana-hloko o kenngoa ka mokhoa o itšetlehileng ka lithethefatsi tsohle tsa tlhekefetso ka ho noa joala / ho tlosoa, 'me sena se nkoa e le ntho e tloaelehileng, ho khothalletsa ho noa lithethefatsi tse feteletseng ka mokhoa o fosahetseng o matlafatsang (ke hore, boemo bo sithabetsang maikutlong; ; ; ).

Le hoja litšebelisano pakeng tsa lithethefatsi tsa tlhekefetso le lijo li 'nile tsa ithutoa ka ho pharaletseng mabapi le mehaho ea bona e matlafatsang (e leng, ho ja lijo tse feteletseng tse hlahisoang ke ho fumana phello e ntle; ; ; ; ; ) Khopolo-taba ea hore ho ja ka mokhoa o feteletseng ho ka fella ka mokhoa oa 'ho iphekola' ho kokobetsa boemo bo sithabetsang ba maikutlo bo amanang le ho khaotsa ho ja lijo tse hlabosehang haholo ha e rutoe haholo (; ; ).

Re kile ra bontša hore ho itokolla ho bolokehi bo sa foleng, bo pakeng tsa lijo tse natefisang haholo ho etsa hore ho hiroe mokhatlo oa CRF oa extrahypothalamic le ho hlaha ha CRF1 ho itšetlehile ka mokhoa o feteletseng oa ho ja lijo tse natefisang, hypophagia ea lijo tse amohelehang tse ling tse amohelehang, le boitšoaro bo kang ba boithaopo nakong ea boithaopo ().

Leha ho le joalo, bopaki bo sebetsang bo mabapi le hore na sebaka sa boko ke sefe se ikarabellang bakeng sa CRF1 ho itšetleha ka boitšoaro bo itšetlehileng ka mekhoa ea boipheliso e bakoang ke ho ja lijo tse fokolang ha ho e-ba teng. Ka hona, thuto ena e ne e ikemiselitse ho khetholla hore na ho hanyetsanoa hoa sebaka sa CRF1 li-receptors ka hare ho khubu ea bohareng ea amygdala (CeA), nucleus ea basolateral ea amygdala (BlA) kapa sebaka sa bethe sa stria terminalis (BNST) se khonne ho thibela ho ja haholo ka lijo tse monate haholo, hypophagia e tsoelang pele khama, le boitšoaro bo kang ba boitšoaro. Ho phaella moo, phuputso ena e ne e rerile ho tseba hore na polelo ea CRF ho CeA, BlA, le BNST e ne e ekelitsoe lijong tsa likoloi ha li bapisoa le litaolo, ho sebelisa immunohistochemistry. Le hoja nakong e fetileng re bontšitse hore ho tlohela lijo tse monate ho amahanngoa le ho eketseha ha polelo ea CRF ho CeA, kamoo BlA le BNST li anngoeng ke libaesekele tsa lijo hajoale li sa tsejoe.

LISEBELISOA LE MEKHOA

Lihlooho

Lipoe tsa banna ba Wistar (n= 140, eo lingaka tsa 33 bakeng sa liteko tsa CeA, likhopo tsa 46 bakeng sa liteko tsa BlA, likhopo tsa 39 bakeng sa liteko tsa BNST, le likhopo tsa 22 bakeng sa teko ea immunohistochemistry; Letlapa le tlatsetsang 1), e lekanang le 180-230 g le matsatsi a 41-47 ha a fihla (Charles River, Wilmington, MA, USA), e ne e le masoha a neng a lula ka har'a terata, li-cages tsa polasetiki (27 × 48 × 20 cm) ka leseli la 12 h potoloho (e khantšang lihora tse 1100), ka mokelikeli o amohelehang oa AAALAC- (60%) le ho laola mocheso (22 ° C) vivarium. Li-rats li ne li le joalo ad libitum ho fumana k'hamphani ea lijo-thollo (Harlan Teklad LM-485 7012 ea lijo; 65% kcal, li-carbohydrate, 13% mafura, 21% protheine, matla a metaboleng 310 cal / 100 g; Harlan, Indianapolis, IN, USA) le metsi ntle le ho hlalosoa . Mekhoa e sebelisoang thutong ena e latela Mokhatlo oa Sechaba oa Tataiso ea Bophelo bakeng sa Tlhokomelo le Tšebeliso ea Liphoofolo Tsa Liphoofolo (NIH khatiso ea 85-23, e ntlafalitsoeng 1996) le Melao-motheo ea Laboratory ea Litlhare tsa Liphoofolo, mme e amoheloa ke Boston University Medical Campus Institutional Komiti ea tlhokomelo ea liphoofolo le ea ho sebelisa.

lithethefatsi

R121919 (3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo [2,3-a] pyrimidin-7-amine, NBI 30775) e entsoe ka mokhoa o hlalositsoeng ). R121919 ke CRF e nang le matla, eseng peptide, e phahameng1 receptor antagonist (Ki= 2-5 nM), e bonts'ang mosebetsi o fokolang oa 1000-fold ha u le CRF2 receptor, proteni e tlamang CRF, kapa mefuta e meng ea 70 ea li-receptor (). R121919 e ile ea qaptjoa ka metsi e sebelisa 18: 1: 1 motsoako oa saline: ethanol: cremophor.

Liteko tsa Boitšoaro

Lipapatso tse lumellang lijo tse fetotsoeng habonolo

Ho fihlella ho ad libitum mefuta e metle ea lijo e entsoe joalokaha ho hlalositsoe pele (, , ; ). Ka bokhutšoanyane, kamora ho hlonepha, likhoto li ile tsa aroloa ka lihlopha tse peli tse lekanang le lijo, boima ba 'mele, le phepo e nepahetseng ea matsatsi a fetileng a 3-4. Sehlopha se seng se ile sa fuoa ad libitum phihlello ea ho ja li-chow (Chow) ka matsatsi a 7 ka beke (Chow / Chow, sehlopha sa taolo ea thuto ena) ha sehlopha sa bobeli se ne se fuoa monyetla oa ho fumana mahala mahala bakeng sa matsatsi a 5 ka beke, se lateloa ke matsatsi a 2 a ad libitum Lijong tse monate haholo, tse natefisang chokolete, tse nang le phepo e phahameng. Chow / e khoneha sehlopha). Liteko tsohle tsa boits'oaro li entsoe ka likhoto tse neng li jele libaesekele bonyane libeke tse 7. Lijo tsa 'chow' e ne e le chow e hlalositsoeng kaholimo ea poone e tsoang Harlan, athe lijo tse hlabosang e ne e le phepo e phethehileng, e nang le tatso ea chokolete, e nang le sucrose e phahameng (50% kcal), lijo tse thehiloeng ho AIN-76A tse tšoanang le tsa macronutrient boholo le matla a matla ho lijo tsa chow (foromo e nang le tatso ea chokolete 5TUL: 66.7% kcal carbohydrate, mafura a 12.7%, liprotheine tse 20.6%, matla a nang le matla a 344 kcal / 100 g (Lijo tsa Teko, Richmond, IN, USA) e entsoe ka mokhoa o nepahetseng oa 45 mg lipelete tsa lijo ho eketsa khetho ea tsona). Bakeng sa bokhutšoane, matsatsi a 5 a pele (chow feela) le matsatsi a ho qetela a 2 (chow kapa e khahlisang ho latela sehlopha sa liteko) tsa beke ka 'ngoe ho buuoa ka tsona litekong tsohle joalo ka C 'me P mekhahlelo. Lijo tse nang le phepo li fanoe ho GPF20 'J'-feeders (Ancare, Bellmore, NY, USA). Lijo li ne li sa fumanehe ka nako e le ngoe.

Liteko tsa kenyelletso ea lijo

Likhoto li ile tsa fuoa lijo tse lekantsoeng ka tlung ea tsona malapeng nakong ea ho potoloha ho lefifi. Ho ile ha fanoa ka kalafo ka likhoto tse neng li jeoa ka nako ea libeke tsa 7 ha li ne li qala ho fumana lijo tse matlafatsang (C→P phase), kapa lijong tsa chowon (P→C karolo). R121919 e ne e le microinfuse bilaterally ka hare ho CeA, BlA, kapa BNST (0, 0.5, and 1.5 μg / side, 0.5 μl / side, 30-min pre-kalafo ea kalafo) e sebelisa meralo e sa sebetseng kahare ho sekepe sa Latin.

Teko ea lebokose le lefifi-le lefifi

Likhoto li ile tsa lekoa bakeng sa 10 min ka lebokoseng le nang le mahlaseli a lefifi (50 × 100 × 35 cm) eo kahare ho moo khanya ea mokoloto (50 × 70 × 35 cm) e bonesitsoeng ke khanya ea 60. Lehlakore le lefifi (50 × 30 × 35 cm) le ne le e-na le sekoahelo sa opaque le ∼0 lux ea khanya. Likarolo tsena tse peli li ne li hokahane ke monyako o bulehileng o neng o lumella lihlooho hore li tsamaee ka bolokolohi lipakeng tsa tsona. Teko e etsahetse kamora bonyane libeke tsa 7 tsa phetoho ea lijo, 5-9 h kamora phetoho e tsoang ho lijo tse matlafatsoang ho ea lijong tsa chowon (P→C karolo); Ntlha ena ea nako e netefatsa ho ba teng ha boits'oaro bo ts'oanang le ho tšoenyeha ho tlisoang ke lijo tse fumanehang habonolo ho Chow / e khoneha likhoto (, ). Likhoto li ne li bolokiloe ka har'a anteroom e khutsitseng, e lefifi bonyane 2 h pele ho liteko. Lerata le lesoeu le ne le le teng hohle ho lula le ho hlahlojoa. Ka letsatsi la liteko, likhoto li ne li le microinfuse bilotally le R121919 ka har'a CeA, BlA, kapa BNST (0, 0.5, le 1.5 μg / side, 0.5 μl / side) 30 min pele e kenngoa kamoreng e lefifi e shebileng monyako. 'me boitšoaro bo ile ba rekota video bakeng sa ho fumana lintlha hamorao. M kalafo e ile ea fanoa ho sebelisoa moralo oa mahareng. Nako e sebelisitsoeng ka kamoreng e bulehileng e ne e lekantsoe e le letšoao la boits'oaro bo kang ho tšoenyeha. Lisebelisoa li ile tsa hlakoloa ka metsi 'me tsa omisoa ka mor'a thuto ka' ngoe.

Opereishene ea Intracranial, Ts'ebetso ea Microinfusion, le Keketso ea Cannula

Opereishene ea Intracranial

Likhoto li kentsoe ka mokhoa o ikhethileng ka li-cannulas tse kopaneng habeli joalokaha ho hlalositsoe pele (; ; ). Ka bokhutšoanyane, tšepe e sa hloekang, li-cannulas tse tataisang (24 gauge, Plastics One, Roanoke, VA, USA) li theotsoe ka bophara ba 2.0 mm kaholimo ho CeA, BlA, kapa BNST. Likurufu tse 'ne tsa mabenyane a tšepe e sa hloekang li ile tsa hokelloa lehateng la rat ho potoloha cannula. Ho ile ha sebelisoa lehoakhoa la meno le khutlisetsang meno (Henry Schein, Melville, NY, USA) le samente ea acrylic, ho theha motheo o tiisang kanala. Li-cannula tse hokahanang ho tsoa ho bregma e sebeliselitsoeng CeA e ne e le: AP +0.2, ML ± 4.2, DV −7 (ho tloha lehata) e nang le bara ea incisor e behileng 5.0 mm kaholimo ho moeli oa litsobotsi, ho latela atlelase ea ). Litlhophiso tsa cannula tse sebelisitsoeng bakeng sa BlA e ne e le: AP −2.64, ML ± 4.8, DV −6.5 (ho tloha lehata) ka lehata le sephara, ho latela ). Likhokahanyo tsa cannula tse sebelisitsoeng bakeng sa BNST e ne e le: AP −0.6, ML N 3.5, DV N4.8 (ho tloha lehata) ka sephaka se sephara le angle e sekameng ea 14 °. Sesebelisoa sa dummy setaele sa tšepe (Plastiki ea Pele) se ile sa boloka cannula e le matla. Kamora ho buuoa, likhoto li ile tsa lumelloa nako ea ho hlaphoheloa ea matsatsi a 7, eo ka eona e neng e sebetsoa ka mehla.

Ts'ebetso ea Microinfusion

Lithethefatsi li ile tsa sebelisoa ka bongata bokong ba likhoto joalokaha ho hlalositsoe pele (; ). Bakeng sa intracranial microinfusion, seretse sa dummy se tlositsoe ho cannula ea tataiso, 'me sa nkeloa sebaka ke 31-gauge ironset injector e neng e kenya 2 mm ka nqane ho ntlheng ea tataiso ea cannula; injector e ne e hokahantsoe ka PE 20 tubing ho Hamilton microsyringe (Hamilton, Reno, Nevada) e tsamaisoang ke pompo ea methapo e mengata ea syringe (KD Saense / Biooloji ea Likepe, Holliston, MA, USA). Li-Microinfusions li entsoe ka 0.5 volumel bophahamo bo hlahisitsoeng ka 2 min; Ho ne ho setse li-injecter sebakeng sa 1 motsotso o mong oa ho fokotsa ho khutla.

Sebakeng sa Cannula

Sebaka sa Cannula se netefalitsoe qetellong ea liteko tsohle (bona Setšoantšo sa 1). Lihlooho li ne li anesthetised (isoflurane, 2-3% ka oksijene) 'me li tšeloa ka bongata ka sefuba 4% paraformaldehyde (PFA) ka metsing (pH 7.4) le microinfuse e nang le Cresyl violet (0.5 μl / side). Li-brains li ne li kenngoa bosiu bosiu ho 4% PFA mme li lekantsoe ho 30% sucrose ho PFA. Likarolo tsa Coronal tsa 40 μm li ile tsa bokelloa li sebelisa cryostat (Thermo Science Science HM-525) mme ho beoa ho netefalitsoe tlasa microscope. Lithuto tse 40 (14 tsa CeA, 16 bakeng sa BlA, le 10 bakeng sa BNST) ha lia ka tsa kenyelletsoa tlhahlobisong ka lebaka la ho beoa ka mokhoa o fosahetseng oa cannula. Lintlha tse tsoang ho se behiloeng ka nepo li ile tsa hlahlojoa ho thusa ho toloka boemo ba litlamorao tsa sebaka seo.

Setšoantšo sa 1 

Ho taka likarolo tsa likotoana tsa likhoto. Matheba a emela libaka tsa ente bohareng ba amygdala (CeA) (a), khubu ea basolateral ea amygdala (BlA) (b) le khubu ea bethe ea stria terminalis (BNST) (c) e kenyellelitsoeng tlhahlobisong ea data. ...

CRF Immunohistochemistry

Ts'ebetso ea boitšoaro, litlolo, le bohloeki

Likhoto (n= 22) li ne li ja li-cycled ka libeke tsa 7, li sa phekolehe, 'me li entsoe 2-4 h ka mor'a hore li fetoloe ho tsoa lijong tse matlafatsoang ho ea lijong tsa chow.P→C mohato) kapa ho tloha ho ja lijo tse matlafatsang ho ea lijong tse fumanehang hantle (C→P karolo). Likhoto li ile tsa felisoa ntle ho tšibollo ea mali 'me tsa hlahisoa ka letsoai le letsoai + 2% (w / v) sodium nitrite (pH = 7.4),' me ka 4% paraformaldehyde buffered ho Borax (pH = 9.5). Likhoto li ile tsa hlakoloa 'me masapo a bokelloa hang-hang, a beoa ∼20 ml ea 4% PFA,' me a bolokoa ka 30% sucrose ho 4% PFA tharollo ho 4 ° C ho fihlela satellite.

Bakeng sa pono ea CRF, boko bo ile ba khaoloa likarolo tse 40 μm tsa li-coronal ho sebelisoa cryostat mme ka mor'a moo tsa bolokoa ka cryoprotectant ho -20 ° C. Karolo e 'ngoe le e' ngoe ea botšelela (240 μm ka thoko) ea CeA, BlA le BNST kaofela e ile ea khethoa ka mokhoa o hlophisehileng mme ea sebetsoa bakeng sa immunocytochemistry. Likarolo tse phaphametseng mahala li ile tsa hlatsuoa ka letswai la potassium phosphate (KPBS). Kamora ho hlatsuoa ha pele, likarolo li ile tsa amohela poloko ho 0.3% ea hydrogen peroxide KPBS tharollo ea metsotso e 30 ho thibela peroxases e sa feleng. Likarolo li ile tsa hlatsuoa hape 'me tsa beoa ka tharollo ea thibelo (3% serum e tloaelehileng ea poli, 0.25% Triton X100, le 0.1% ea likhomo serum albumin) bakeng sa 2 h. Likarolo li ile tsa fetisetsoa ho antibody ea mantlha (1: 100 dilution, anti-CRF (sc-10718), Santa Cruz Biotechnology) ho thiba tharollo le ho kenella bakeng sa 72 h ho 4 ° C. Kamora ho hlatsuoa ho eketsehileng, likarolo li ile tsa kenella ho antibody ea bobeli (1: 1000 dilution, biotinylated anti-rabbit (BA-1000) Vector Laboratories, Burlingame, California) ho thiba tharollo ea 2 h ka mocheso oa kamore. Likarolo li ile tsa hlatsuoa ebe li kenngoa ka tharollo ea avidin-biotin horseradish peroxidase ABC (Vector Laboratories) ho thiba tharollo ea h 1. Likarolo li ile tsa kenella ka ts'ebeliso ea kit ea diaminobenzidine substrate kit (Vector Laboratories) ho latela litaelo tsa moetsi mme hang ha karabelo e se e felletse likarolo li hlatsuoe KPBS, li maneoa holim'a li-slide ebe li lumelloa ho omella bosiu bo le bong. Letsatsing le hlahlamang, li-slide li ile tsa felloa ke metsi ka lebaka la likhakanyo tsa joala tse koahetsoeng 'me tsa koaheloa li sebelisoa ke DPX mountant (Electron Microscopy Science, Hatfield, PA, USA).

Quanuction ea lihlahisoa tsa sele ea CRF

Quanifying ea lihlahisoa tsa selefounu ea CRF + e entsoe ho latela mokhoa o sa tsitsang oa stereology. Ho ile ha hlahlojoa letoto la likarolo bakeng sa sehlopha ka seng. Likarolo li ile tsa hlahlojoa ho sebelisoa mochine o bapalang li-microscope oa Center oa Boreki (Center Valley, PA, USA) o nang le kh'amera ea Rotiga 51R live video (QImaging, Surrey, BC, Canada), phase-axis MAC2000 XYZ motorated (Ludl Electronics, Hawthorne, NY, USA), le mochine o sebetsang oa likhomphutha. Lipalo tsohle tsa sele li entsoe ka li-slide tse khoutu ke mofuputsi ea sa boneng maemo a kalafo. Sebaka se seng le se seng se ne se hlalositsoe ka mokhoa o hlakileng setšoantšong se seng le se seng se khethiloeng ka mokhoa o sa lekanyetsoang se sebelisang module ea software ea patlisiso ea Stereo Inarcherator (MicroBrightField, Williston, VT, USA). Liphetoho tsohle li ne li huleloa ka matla a tlase ho sebelisoa sepheo sa Olimpiki ea Ntoa ea Ntoa ea 6000X ka lipalo tsa 2 tsa lipalo mme li baliloe ho sebelisoa sepheo sa Olimpi UPlanFL N 0.08X ka lipalo tsa XertUMX tsa lipalo. Moralo oa gridi le sebopeho sa ho bala li ne li behiloe ho 40 × 0.75 μm. Sebaka se sirelelitsoeng sa 275 Xm le bophahamo ba dissector tsa 160 μm li ile tsa sebelisoa. Likarolo tse neng li le mongobo qalong li ne li khaoloa ka botenya ba lebitso la 2 μm. Ho se sireletsehe le ho hola ho fella ka likarolo tse fetotsoeng, tse neng li lekantsoe sebakeng se seng le se seng sa lipalo. Botebo ba karolo e bohareng bo kopantsoe ke software mme bo sebelisoa ho hakanya palo eohle ea sebaka sa sampole le palo e felletseng ea lisele tsa CRF +.

Tlhahlobo ea Litekanyetso

Seithuti t-liteko li sebelisitsoe ho sekaseka lintlha ka mekhahlelo e 'meli. Li-ANOVA li ile tsa etsoa ho sekaseka lintlha ka maemo a fetang a mabeli. Ho latela phello ea bohlokoa ea li-omnibus tsa li-ANOVA (p<0.05), LSD ea Fisher post hoc liteko tsa papiso li sebelisitsoe. Teko ea Dunnett e sebelisitsoe ho fumana hore na R121919 e ja lijo tse tloaelehileng Chow / e khoneha likhoto ho phekoloa likoloi Chow / Chowmaemo a hloahloa. Li-package / graphic package tse sebelisitsoeng e ne e le Systat 11.0, SigmaPlot 11.0 (Systat Software, Chicago, IL, USA), InStat 3.0 (GraphPad, San Diego, CA, USA), Statistica 7.0 (Statsoft, Tulsa, OK, USA), le PASW Lipalo 18.0 (SPSS, Chicago, IL, USA).

LIPOTSO

Litlamorao tsa Microinfusion ea R121919 ho CeA

Ho ja lijo tse matlafatsang haholo

Ho tseba hore na CRF1 li-receptors tsa CeA tse arolelanang ho ja lijo tse matlafatsang ka har'a lijo tse tsamaisoang ka likhakanyo, rona sebaka sa li-microinfuse ka ho khetheha CRF e ikhethileng1 receptor antagonist R121919 sebakeng sena sa boko le ho lekanya ho ja lijo qalong ea P mohato. Joalokaha ho bontšitsoe Setšoantšo sa 2a, ho ja lijo tse matlafatsoang ke likoloi Chow / e khoneha likhoto li ne li phahame habeli ho feta taolo e fuoeng ke chowon Chow / Chow likhoto. Khopolo-taba ea CeA CRF1 li-receptors li thibetse ka botlalo mokhoa ona oa ho ja lijo tse matlafatsoang ka ho Chow / e khoneha likhoto, ntle le ho ama ho kenella ha lijo ho likhoto tsa taolo (Chow / Chow, F (2, 20) = 0.72, NS; Chow / e khoneha, F (2, 14) = 5.02, p Post hoc papiso e senotse hore tekanyetso e phahameng ka ho fetisisa ea R121919 (1.5 μg / lehlakoreng) e fokotsitse haholo lijo tse ka nkoang habonolo ha li bapisoa le koloi e kenang Chow / e khoneha likhoto. Tloaelo ea Chow / e khoneha litoeba tse latelang microinfusion ea 1.5 μg / lehlakoreng litekanyetso li ne li sa fapana haholo le tšebeliso ea meriana e kentsoeng koloi Chow / Chow likhoto. Ho netefatsa lintlha tse ikhethang tsa litlamorao ho CRF1 li-receptors ho CeA, ha ho na phello e ileng ea bonoa ho jang lijo tsa lihlooho tsa "cannulae" tse sa sebetseng hantle.Chow / e khoneha, F (2, 2) = 4.32, NS).

Setšoantšo sa 2 

Liphetoho tsa microinfusion ea corticotropin-ekhethollang factor-1 (CRF)1) receptor antagonist R121919 (0, 0.5, 1.5 μg / side) karolong e bohareng ea amygdala (CeA) ka ho ja ho feteletseng lijo tse matlafatsang, hypophagia ea kamehla ...

Hypophagia ea lijo tse tloaelehileng tsa chow

Ho tseba hore na CRF1 li-receptors ka CeA li loants'oa hypophagia ea chow ho ja lijong tsa cystled, re le microinfuse R121919 sebakeng sena sa boko mme ra lekanya lijo tse ngata qalong ea C mohato. Joalokaha ho bontšitsoe Setšoantšo sa 2b, ho jella likoloi tse tsamaisoang Chow / e khoneha likhoto e ne e le ∼1 / 3 ea ts'ebeliso ea likoloi tse tšoaroang Chow / Chow likhoto (hypophagia). Phekolo ea R121919 ha ea ka ea ama hypophagia ea chow e tloaelehileng ho Chow / e khoneha likhoto (Chow / e khoneha, F (2, 12) = 0.14, NS). Ho netefatsa liphetho tse fumanoeng P phase, R121919 microinfusion ho CeA ha ea ka ea ama tšebeliso ea tahi ea chow Chow / Chow likhoto (Chow / Chow, F (2, 20) = 0.01, NS).

Boitšoaro bo bobebe ba ho khaotsa bo tsosang takatso

Ho tseba hore na CeA CRF1 li-receptors li hokahanya boemo bo bobe ba maikutlo bo susumetsoang ke ho tlosa lijo tse fumanehang habonolo lipapaling tse tsamaeang ka seketsoana, rona webinete e fumanehang ka ho khetheha R121919 sebakeng sena sa boko mme ra lekanya boitšoaro bo kang ba ho tšoenyeha re sebelisa teko ea lebokose le lefifi la 5 h ho C mohato. Joalokaha ho bontšitsoe Setšoantšo sa 2c, litoeba tse tlositsoeng phepong e sa feleng, ea nakoana ea lijo tse fumanehang habonolo li bontšitse ho fokotseha ho hoholo ha nako e sebelisitsoeng kahare ho lebokose le lefifi la lefifi. Microinfusion ea 1.5 μg / lehlakoreng la R121919 ho CeA, tekanyo e fokotsitseng ho ja lijo tse matlafatsang ka mokhoa o phethahetseng, e thibile ka botlalo boits'oaro bo joalo ba ho tšoenyeha joalo ka ho eketsa nako e sebelisitsoeng sebakeng se bobebe sa lebokose ho Chow / e khoneha likhoto, ntle le ho ama boits'oaro ho Chow / Chow likhoto (DOSE: F (1, 24) = 4.40, p<0.05). Ho netefatsa bonnete ba litlamorao tsa CRF1 li-receptors ho CeA, ha ho na phello e ileng ea bonoa mabapi le tšebeliso ea lijo tsa lithuto tse nang le cannulae e sa sebetseng (DOSE: F (2, 2) = 4.32, NS).

Liphello tsa Microinfusion ea R121919 ho BlA

Ho ja lijo tse matlafatsang haholo

Ho fumana hore na BlA CRF1 li-receptors li boelana le ho ja ka bongata lijo tse matlafatsoang lijong tsa li-cycled tse tsamaeang le likhakanyo, rona sebaka sa li-microinfused ka ho khetheha R121919 sebakeng sena sa boko mme ra lekanya ho ja lijo qalong ea P mohato. Ho fapana le se ileng sa bonoa kamora ho tsamaisoa ha R1219191 ho CeA, joalo ka ha ho bonts'itsoe Setšoantšo sa 3a li-bilinal microinfusion tsa CRF e ikhethileng1 antagonist ea antagonist ho BlA ha ea ka ea ama khaello ea lijo tse fumanehang kahare ho Chow / e khoneha likhoto (Chow / e khoneha, F (2, 26) = 1.56, NS). Ka mokhoa o ts'oanang, ts'ebeliso e tloaelehileng ea chow Chow / Chow likhoto ha lia ka tsa angoa ke R121919 microinfusion (Chow / Chow, F (2, 18) = 0.52, NS).

Setšoantšo sa 3 

Liphetoho tsa microinfusion ea corticotropin-ekhethollang factor-1 (CRF)1) receptor antagonist R121919 (0, 0.5, 1.5 μg / side) bokong ba basolateral ea amygdala (BlA) ka ho ja ho feteletseng lijo tse matlafatsang, hypophagia ea kamehla ...

Hypophagia ea lijo tse tloaelehileng tsa chow

Ho tseba hore na CRF1 li-receptors ho BlA mediate hypophagia ea chow ho likhoto tse tsamaeang ka lebelo, re butse R121919 sebakeng sena sa boko mme ra lekanya lijo tse ngata qalong ea C mohato. Joalokaha ho bontšitsoe Setšoantšo sa 3b, keketseho e kholo ea tšebeliso ea kamehla ea chow e ile ea bonoa ka mor'a ho latela microinfusion ea CRF1 receptor antagonist in the BlA of Chow / e khoneha likhoto (Chow / e khoneha, F (2, 26) = 4.46, p<0.05). Ehlile, lethal dose e phahameng ka ho fetisisa (1.5 μg) ea R121919 microinfused ho BlA nakong ea C Karolo e ntlafalitse haholo ts'ebeliso ea phepo e tloaelehileng ea 221.1 ± 33.1 (M ± SEM) lekholong ha e bapisoa le kalafo e ts'oaroang likoloi Chow / Chow likhoto. R121919 e kentsoe, empa ha ea ka ea thibela ka ho felletseng, hypophagia e tsoang ho tsoa ho lethal dose e phahameng ka ho fetesisa. Ho netefatsa lintlha tse fumanoeng ho P phase, R121919 microinfusion ha ea ka ea ama ho kenella hangata kahare ho Chow / Chow likhoto (Chow / Chow, F (2, 20) = 0.25, NS). Ho netefatsa lintlha tse ikhethang tsa litlamorao ho CRF1 li-receptors BlA, ha ho na phello e ileng ea bonoa ho ja lijo tsa lihlooho tse nang le cannulae e sa sebetseng (Chow / e khoneha, F (2, 8) = 0.50, NS).

Boitšoaro bo bobebe ba ho khaotsa bo tsosang takatso

Ho fumana hore na BlA CRF1 li-receptors li hokahanya boemo bo bobe ba maikutlo bo susumetsoang ke ho tlosa lijo tse matlafatsoang ka har'a litoeba tse potolohileng, re sebelisa sebaka sa li-microinfuse ka ho khetheha R121919 sebakeng sena sa boko mme ra lekanya boits'oaro bo kang 5 h ho kena C mohato. Joalokaha ho bontšitsoe Setšoantšo sa 3c, lijo tse fumanehang habonolo Chow / e khoneha likhoto li qetile nako e fokolang kamoreng e bobebe ha e bapisoa le Chow / Chow likhoto (DIET: F (1, 23) = 84.03, p<0.001). R121919, e kenngoeng microinfused ho BlA, ha ea ka ea ama haholo nako e sebelisitsoeng sebakeng sa mabone (DOSE: F (1, 39) = 0.01, NS).

Liphello tsa Microinfusion ea R121919 ho BNST

Ho ja lijo tse matlafatsang haholo

Ho tseba hore na BNST CRF1 li-receptors li kenyelletsa ho ja ka bongata lijo tse matlafatsoang lijong tsa li-cycled tse tsoang ka har'a roko, R121919 e ne e le sebaka sa mantlha se bitsoang microinfuse sebakeng sena sa bokong mme takatso ea lijo e lekantsoe qalong ea P mohato. Joalokaha ho bontšitsoe Setšoantšo sa 4b, microinfusion e kopaneng ea CRF e ikhethileng1 receptor antagonist ho BNST ha e a ka ea ama haholo ho ja habonolo ha lijo Chow / e khoneha likhoto (Chow / e khoneha, F (2, 18) = 0.33, NS). Ka mokhoa o ts'oanang, ts'ebeliso e tloaelehileng ea chow Chow / Chow likhoto ha lia ka tsa angoa ke R121919 microinfusion (Chow / Chow, F (2, 20) = 1.03, NS).

Setšoantšo sa 4 

Liphetoho tsa microinfusion ea corticotropin-ekhethollang factor-1 (CRF)1) receptor antagonist R121919 (0, 0.5, 1.5 μg / lehlakoreng) ka kamoreng ea bethe ea "stria terminalis" (BNST) ka ho ja ho feteletseng lijo tse matlafatsang, hypophagia ea ...

Hypophagia ea lijo tse tloaelehileng tsa chow

Ho tseba hore na BNST CRF1 li-receptors li hokahanya hypophagia ea lijo tse jeoang ka har'a litoeba tse potolohileng, re kentse R121919 sebakeng sena sa boko mme ra lekanya tšebeliso ea lijo qalong ea C mohato. Joalokaha ho bontšitsoe Setšoantšo sa 4a, R121919 microinfusion ha ea ka ea ama ho kenella hangata kahare ho chow Chow / Chow likhoto (Chow / Chow, F (2, 14) = 0.03, NS). Ka mokhoa o ts'oanang, kalafo ea R121919 ha ea ka ea ama hypophagia ea chow e tloaelehileng ho Chow / e khoneha likhoto (Chow / e khoneha, F (2, 20) = 0.27, NS).

Boitšoaro bo bobebe ba ho khaotsa bo tsosang takatso

Ho tseba hore na BNST CRF1 li-receptors li hokahanya boemo bo bobe ba maikutlo bo susumetsoang ke ho tlosa lijo tse matlafatsoang ka har'a litoeba tse potolohileng, re sebelisa sebaka sa li-microinfuse ka ho khetheha R121919 sebakeng sena sa boko mme ra lekanya boits'oaro bo kang 5 h kamora ho fetoha P→C mohato. Joalokaha ho bontšitsoe Setšoantšo sa 4c, lijo tse fumanehang habonolo Chow / e khoneha likhoto li qetile nako e fokolang kamoreng e bobebe ha e bapisoa le taolo Chow / Chow likhoto (DIET: F (1, 17) = 17.11, p<0.01). R121919, likokoana-hloko tse kopantsoeng ka bongata ka lethal dose ea 1.5 μg / lehlakoreng ho BNST ha ea ka ea ama haholo nako e sebelisitsoeng sebakeng se bobebe (DOSE: F (1, 33) = 0.47, NS).

CRF Immunohistochemistry

Setšoantšo sa 5 e bonts'a li-micrograph tsa baemeli ba lisele tsa CRF + ho CeA, BlA, le BNST ho Chow / Chow 'me Chow / e khoneha likhoto, latelang ad libitum mokhoa o monate oa ho ja lijo tse fetotsoeng. Tlhahlobo ea immunoreactivity ea CRF ea CeA e bontšitse hore phapang e kholo lipakeng tsa Chow / e khoneha 'me Chow / Chow likhoto nakong ea C le P phase (F (2, 19) = 4.19, p<0.05). Ha ho phapang ea lipalo-palo lipakeng tsa lihlopha e ileng ea bonoa ho BlA (F (2, 17) = 1.13, NS) kapa BNST (F (2, 19) = 1.16, NS).

Setšoantšo sa 5 

Likokoana-hloko tse emelang corticotropin-releasing factor (CRF) mokokotlong oa mokokotlo oa amygdala (CeA) (a-d), basolateral nucleus ea amygdala (BlA) (e-h), le khubu ea boroko ea stria terminalis (BNST ) (i-l) ...

TŠOHLOA

Phuputso ena e etselitsoe ho tsebahatsa sebaka sa boko se ikarabellang bakeng sa ho ja lijo tse matlafatsang haholo li-rats tlasa mofuta o mong oa lijo. Seo re se fumaneng se paka karolo e kholo ho CeA ho ho ja lijo tse matlafatsang haholo. Ntle le moo, re bonts'a hore Sisteme ea CRF ho BlA, ho fapana le CeA, e na le seabo morerong oa ntlafatso o etsahalang ha o theoha tekanyong ea moputso oa lijo.

Re kile ra bonts'a hore nako le nako ho natefeloa ke ho ja lijo tse matla tse tsoekere, tse nang le phepo e ntle haholo, ho lebisa ho jang lijo tse matlafatsang hape le hypophagia e matla ea ho tlohela lijo e nang le phepo e tloaelehileng le boits'oaro bo joalo ka (; , ). Ho ja haholo ho hlokometsoeng mona ho khothaletsoa hore ho khannoe ke boemo bo bobe ba maikutlo bo susumetsoang ke liketsahalo tsa khafetsa tsa ho itlhahisa ho matla lijong tse fumanehang habonolo ka extrahypothalamic CRF-CRF1 Mechini e amohelang tsamaiso ea receptor, e ts'oanang le ts'ebetso ea 'kindling' e bakang mathata a lemalloang (; ; ; ).

Liphetho tsa thuto ena li bonts'a CRF1 li-receptors tsa CeA le BlA ka tsela e fapaneng li ikamahanya le phepelo ea phepo le boits'oaro bo ts'oanang le boits'oaro ba phepo e sa foleng ea li-cycled. Tsamaiso ea CRF e khethang1 receptor antagonist ka hare ho CeA e thibetse ho ja ho feteletseng le boits'oaro bo kang ho tšoenyeha ho Chow / e khoneha likhoto, ntle le ho ama hypophagia ea lijo tse sa amoheloang, tse tloaelehileng. Ho khahlisang, tsamaiso ea R121919 ho BlA, e fumaneng hypophagia ea lijo tse sa bateng ho ja (ke hore, ho eketsa ho ja kamehla) ho Chow / e khoneha likhoto, ntle le ho ama ho ja haholo kapa boits'oaro bo kang bo tšoenyang. Ha microinfuse ho BNST, R121919 ha ea ka ea ama mefuta e meng le e meng e lekantsoeng kahare Chow / e khoneha likhoto (ho ja haholo lijo tse matlafatsang haholo, ho ja lijo tse tloaelehileng tsa kamehla le mokhoa o mongata oa ho itlosa bolutu). Litholoana tse bonoang tsa pharmacological li ile tsa ikhethela Chow / e khoneha likhoto hobane R121919, li-microinfuse kahara CeA, BlA, kapa BNST ea Chow / Chow laola likhoto, ha e na phello. Ka hona, CRF-CRF1 Sistimi ea receptor ea CeA le BlA li shebahala ka mokhoa o fapaneng le litlamorao tsa boits'oaro bo bakoang ke ho ja lijalo ka linako tse ling. Ka lehlakoreng le leng, CRF-CRF1 Sistimi ea receptor ea BNST ha e bonahale e nka karolo mekhoeng ea boits'oaro e khothalletsoang ke phetoho e ntle ea lijo.

Liphumano tsa rona tsa boits'oaro le tsa bophelo bo botle li ile tsa tšehetsoa ke bonohe ba hore boits'ireletso ba CRF kahare ho CeA ea Chow / e khoneha likhoto li ile tsa eketseha haholo ha li bapisoa le Chow / Chow laola likhoto, nakong ea ho khaotsa ho tsoa le ho latela mokhoa o mocha oa ho fumana lijo tse fumanehang habonolo (). Ka ho khahlisang, ha ho phapang e kholo ea ts'ireletso ea CRF lipakeng tsa lihlopha e ileng ea bonoa ka har'a BlA kapa BNST. Ho eketseha ha boits'ireletso ba CRF bo bonoang ho CeA ea Chow / e khoneha Likhoto li lumellana le seo re neng re se fumana nakong e fetileng ea hore ho tlohella lijo tse matlafatsang ho amana le tokollo e eketsehileng ea CRF ho CeA (). Leha ho le joalo, ka nepo ho se neng se bontšoa pejana, ho nchafatsa phihlello ea lijo tse matlafatsoang ha hoa ka ha khutlisa polelo ea CRF ho CeA ho laola maemo. Phapang lipakeng tsa sephetho se fumanoeng mona le tlhaiso e fetileng e ka amana le nako e fapaneng ea pokello ea boko, le tharollo e fapaneng ea litsebo tsa mekhoa e amohetsoeng ho lekola polelo ea CRF. Le ha ho le joalo, keketseho e boneng ea polelo ea CRF ho CeA nakong ea ho khaola le ho latela phihlello e nchafalitsoeng ea ho ja lijo tse matlafatsoang e lumellana le litlamorao tse khethiloeng tsa blockade ea boits'oaro bo kang ho tšoenyeha (nakong ea ho khaotsa) le ho ja ka mokhoa o feteletseng (phihlello e nchafalitsoeng) ho Chow / e khoneha likhoto. Ho se lumellane ho totobetseng pakeng tsa lithuto tsena tse peli, ka hona, ho ka fetoleloa ka mokhoa o latelang: nakong ea ha ho natefeloa lijo ho matla, polelo ea CRF e eketseha ho CeA ea lijo tse tsamaeang le likhoto tse bapisoang le taolo mme ke tsona tse ikarabellang bakeng sa ho hlaha ha ts'ebetso e mpe. CeA CRF polelo e ntse e fetotsoe ho fihlela lihora tsa pele tsa phihlello e fumanehang habonolo, e khothalletsang ho ja haholo. Kamora ts'ebeliso e matla ea lijo, CRF e khutlela maemong a taolo ().

Liphetho tsa boitsoaro, litabeng tsa meriana le limolek'hule li bonts'itse ts'ehetso ea maikutlo ea hore CRF-CRF1 Sisteme ea receptor ho CeA e na le karolo ea bohlokoa ho hanyetsanang le maemo a mabe a amanang le ts'oaetso le ho ja lijo tse matlafatsang lijong tsa cystled tse tšoanang le se bonts'itsoeng haholo bakeng sa ts'ebeliso ea joala le lithethefatsi (). Kannete, likhoto tse itšetlehileng ka ethanol li bonts'a tokollo e tsoang kantle ho CRF ho CeA nakong ea ho khaola mme tsamaiso ea mohanyetsi oa CRF receptor ho CeA e khona ho thibela boitšoaro bo ikemetseng ba ethanol nakong ea ho ikhula (; ). Ka mokhoa o makatsang, liphoofolo tse itšetlehileng ka opiate li bonts'a polelo e eketsehileng ea CRF ho CeA nakong ea ho tlohela () le blockade ea li-receptor tsa CRF ho CeA, empa eseng BNST, e fokotsa mats'oao a boitšoaro a ho tlohela (; ). Karolo ea bohlokoa bakeng sa CRF-CRF1 Sistimi ho CeA e boetse e bontšitsoe ho itšetleha ka nicotine. Ha e le hantle, ho ntsoa ha nicotine e kentsoeng ke mecamylamine ho amana le ts'ebetso e kholo ea CRF-CRF1 sistimi ea receptor ho CeA (), le intra-CeA, empa eseng Intra-BlA, microinfusion ea CRF1 antagonist e fokotsa ho phahamisa ho tlosoa hoa nicotine ho monyako oa moputso oa boko (). Ho litoeba tse itšetlehileng ka cannabinoid, ho tlosa chelete esale pele ho amana le ho phahama ho hoholo hoa mahloriso a CRF kantle ho CeA (). Ka kakaretso, bopaki bona bo tšehetsa ka matla khopolo ea hore CRF-CRF1 Sisteme ea receptor ho CeA ke mosireletsi oa bohlokoa oa ts'usumetso e mpe e tlisoang ke ho kenella, hammoho le tšebeliso e mpe ea lithethefatsi le joala nakong ea ts'ehetso. Liphetho tsa rona li holisa tsebo ena ho ja ka bongata lijo tse matlafatsoang, ho fana ka maikutlo a hore li-anuroadaptations lia etsahala.

Liphetho tsa boithuto bona li bonts'a hore lijo tse matlafatsang tse tlisoang ke lijo tse tsoang phepong e nyane ea lijo, li hlahisoa ke micinfusion ka hara BlA ea CRF e ikhethileng.1 receptor antagonist, athe ho ja ho feteletseng le boits'oaro bo ts'oenyehileng joalo ka ha bo anngoe ke kalafo ea lithethefatsi ea intra-BlA. Ho kenya letsoho ho fapaneng ha BlA CRF-CRF1 tsamaiso ea li-receptor liphelong tsa phepo ea ho ja-cycling e fana ka maikutlo a hore hypophagia ea chow e ka emela ts'ebetso ea boits'oaro ntle le boits'oaro bo ts'oanang le ho tšoenyeha. Ho fapana le moo, liphumano tsena li lumellana le khopolo-taba ea hore BlA e kopanya likarolo tsa maikutlo le ts'usumetso ea liketsahalo tse matla haholo. Ho joalo, ho na le bopaki bo bongata ba hore BlA e bohlokoa ka ho hlaka molemong oa ho rarolla litheko tsa tlhabollo ea litheko le likarabo tse tlatselletsang ho phokotso ea meputso (ke hore, Crespi athari, phapano e mpe e latellanang, tefo ea moputso, joalo-joalo; ; ; ), hape, hypophagia e hlahisoang ke phetoho e tsoang ho lijo tse matlafatsoang ho ea lijong tse fokolang tse nang le takatso ea lijo e ka emela ts'ebetso ea matla a hedonic, ho e-na le ts'ebetso e itšetlehileng ea homeostasis (ke hore, e ikemetseng ho tsoa matla a pele ho matla kapa ho phahamisa boima ba 'mele ; , ). Blockade ea CRF1 li-receptors kahare ho BlA, ka hona, li fana ka maikutlo a ho fokotsa ho fokola ha 'mele (ke hore, ho eketsa tekanyo ea lijo) ka ho amohela mokhoa oa ho theoleha o etsahalang ha o tloha ho lijo tse fumanehang habonolo ho fihlela o sa tsotelleng lijo. E amanang le taba ena hape ke ho se lumellane ho hlakileng lipakeng tsa limolek'hule le litlamorao tsa boitshwaro / litoro tse fumanoeng ho BlA. Leha CRF1 antagonist ea li-receptor e khonne ho fokotsa boholo ba "hyp hypoggia" ha e kenngoa ka har'a BlA, ha ho phapang e kholo ea ts'ireletso ea CRF e ileng ea bonoa sebakeng sena ha ho bapisoa litoeba tsa taolo le lijo. Tlhaloso ena e hlakileng e ka hlalosoa ha ho nahanoa hore mekhoa ea tlhabollo e itšetlehileng ka BlA ea meputso e meng e etsahala 'meleng' me e na le bohlokoa ba ho iphetola ha lintho ha ho khethoa lijo tse fanang ka moputso / boleng bo phahameng ka ho fetisisa (). Kahoo, ho ka ba le phetoho ea hore lipuisano tsa lits'ebetso tsena ho BlA ha li hloke neuroadaptations tsamaisong ea CRF (e ts'oanang le e hlokometsoeng ho CeA). Ho ts'ehetsa kelello ena, le ha ho ja ho feta tekano ho hloka ho phahama ka mokhoa o sa tsitsang oa mmele, hypophagia ea chow e khethiloeng e sa sebetseng e etsahala ka mor'a phetoho ea pele ea ho tloha lijong tse matlafatsang haholo ho khutlela ho chow e tloaelehileng.). Ntle le moo, ho bohlokoa ho totobatsa hore, ho latela liphetho tse fumanoeng ka ho enta CRF1 receptor antagonist ho BlA le CeA, CRF1 hypophagia e itšetlehileng ka receptor e hlokometsoeng mona e bonahala e le ts'ebetso e fapaneng ea boits'oaro ho fapana le anhedonia e bonoang ho tloseng lithethefatsi. Leha ho le joalo, ho khaotsa ho matla ho tsoa phihlelong ea lijo tse matlafatsoang ho bontšitsoe ho susumetsa likarabo tse ling tse kang hypohedonic tse kang ho hloka matla ha tlhahlobo e qobelloang le ho fokotseha ho arabela ka kemiso e tsoelang pele ea karolelano (; ).

Hoa hlokomeleha ho bolela hore, leha ho le joalo Chow / e khoneha Likhoto li 'nile tsa ja ka mokhoa o sa foleng ka li-cycled, liphetoho tsa boits'oaro le methapo e bontšitsoeng mona li etsahala nakong ea khatello e matla, ho e-na le ho khaotsa ho ja kamehla. Ho totobatsa ntlha ena ho bohlokoa haholo joalo ka ha ho etsoa lipatlisiso tsa bokhoba ba litheko tse tebileng litlamorao tsa boitshwaro, boteng le boteng vs ho itšila nako e telele ho hlokometsoe (; ). Lithuto tsa nako e tlang li tla ba tsa bohlokoa ho khetholla hore na ho itokolla ho sa ntsane ho le teng ho ka ama litholoana tsa sephetho sa ho ja libaesekele joang.

Ntlha ea bohlokoa ea puisano ke hore na boitšoaro bo fetelletseng ba ho ja lijo boo re bo bonang maemong a mofuta ona oa liphoofolo bo ka nkuoa bo le "bohloka". Phuputsong ea ho lemalla bokhoba ba pelehi, poleloana 'ho qobella' e sebelisitsoe haholo ho hlalosa tšebeliso e fetelletseng ea lithethefatsi nakong ea ho khaotsa, e tsamaisoang ke boemo bo bobe mme e imolohile ha o nchafatsa phihlello ea lithethefatsi (; ). Kamohelo ena ea lentsoe 'ho qobella' e ipapisitse le moralo oa mohopolo oa hore mathata a qobelloang a tšoauoa ka matšoenyeho le khatello ea maikutlo pele a etsa boitšoaro bo qobelloang, le phomolo khatellong ea maikutlo ka ho etsa boitšoaro bo qobelloang (; ). Moelelong oa mofuta oa phoofolo o sebelisitsoeng mona, boitšoaro bo fetelletseng ba ho ja bo ka hlalosoa e le mofuta oa boits'oaro ba 'ho qobella' ha ho fanoa ka bopaki bo phatlalalitsoeng pejana ba hore likhoto tse nang le phihlello e kenang ea lijo tse hlabosang li bonts'a maikutlo a mabe nakong ea ho khaotsa ho ja lijo, tse tsebahalang ka boits'oaro bo ts'oanang le matšoenyeho le boits'oaro bo ts'oenyehileng, bo imolohileng ha o nchafatsa phihlello (, ; ).

Ka bokhutšoanyane, liphetho tsa thuto ena li fana ka bopaki bo matla ba hore CRF-CRF1 Sisteme e amohelang CeA le BlA e na le karolo e fapaneng phapusing ea boits'oaro bo bobe bo bakoang ke phihlello ea nako le nako ea lijo tse fumanehang habonolo. CeA, CRF-CRF1 Sistimi ea li-receptor ke mokena-lipakeng oa bohlokoa oa ho ja ka mokhoa o fetelletseng lijo tse hlabosehang le ts'oaetso e mpe e itšetlehileng ka ho khaotsa ho its'oara, athe ho BlA e kenella likarabo tse ikhethileng tsa lihlooho tse hlahisitsoeng ke phokotso ea moputso.

CHELETE LE HO FIHLELA

Bangoli ba phatlalatsa hore ha ho na likhohlano tsa thahasello.

lumela hore baa fokola

Re leboha Duncan Momaney, Aditi R Narayan, Jina Kwak bakeng sa thuso ea mahlale, le Tamara Zeric ka thuso ea mahlale le bohlophisi. Re boetse re leboha Elena F Crawford ka litlhahiso tse thusang mabapi le CRF immunohistochemistry. Sengoliloeng sena se entsoe hore se khonehe ka linomoro tsa lithuso DA023680, DA030425, MH091945, MH093650, le AA016731, ho tsoa Setsing sa Naha sa Tlhekefetso ea Lithethefatsi (NIDA), Setsi sa Naha sa Bophelo bo Botle ba Kelello (NIMH), le Setsi sa Naha sa Tlhekefetso ea Joala le Tlhekefetso ( NIAAA), ke Peter Paul Career Development Professorship (PC) le Lenaneo la Patlisiso ea Baithuti ba Sekolo se Phahameng sa Boston (UROP). Patlisiso ena e boetse e tšehelitsoe ke Mananeo a Tlhatlhobo a Intramural a Setsi sa Naha sa Tlhekefetso ea Lithethefatsi, le Setsi sa Naha sa Tlhekefetso ea Joala le Tlhekefetso, NIH, DHHS. Litaba tsa eona ke boikarabello ba bangoli ebile ha li bolele maikutlo a semmuso a Mekhatlo ea Naha ea Bophelo.

Mongolo o botlaaseng ba leqephe

 

Boitsebiso bo Eketsehileng e tsamaea le pampiri ho websaeteng ea Neuropsychopharmacology (http://www.nature.com/npp)

 

 

Boitsebiso bo Eketsehileng

Boitsebiso bo Eketsehileng

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