Kufuna Chokoleti Kukukakamizidwa: Gene-Environment Interplay (2015)

  • Enrico Patrono,
  • Matteo Di Segni,
  • Loris Patella,
  • Diego Andolina,
  • Alessandro Valzania,
  • Emanuele Claudio Latagliata,
  • Armando Felsani,
  • Assunta Pompili,
  • Antonella Gasbarri,
  • Stefano Puglisi-Allegra,
  • Rossella Ventur

Lofalitsidwa: March 17, 2015

http://dx.doi.org/10.1371/journal.pone.0120191

Kudalirika

Background

Matenda odyera amawonekera chifukwa cha kuyanjana kwakukulu pakati pa chilengedwe ndi zobadwa, komanso kudyetsa kudya pofuna kuthana ndi zovuta kumayambitsa matenda ambiri.

Zida ndi njira

Ife tinkafanizira kukakamizidwa-monga kudya monga mawonekedwe oletsedwa a zakudya zopatsa phokoso panthawi zovuta pa zovuta za C57BL / 6J ndi DBA / 2J mbewa, zowawa ziwiri zozizwitsa, kudziwa momwe chikhalidwe cha chilengedwe chimayendera pa khalidweli phenotype. Kuwonjezera pamenepo, tinayeseranso kuganiza kuti kupezeka kwapadera kwa D2 receptor (R) ndiko kupezeka kwa chibadwa cha chikhalidwe cha zakudya komanso kuti chilengedwe chimachititsa kuti anthu azidya zakudya zolimbitsa thupi kuti asinthe malingaliro a D2R mu striatum. Kuti titsimikizire izi, tinayesa kufotokoza kwa D1R ndi D2R mu striatum ndi D1R, D2R ndi ma α1R m'madera oyandikana nawo, pafupi ndi kumadzulo.

Results

Kuwonetsera ku chilengedwe kumapangitsa munthu kukakamizidwa-monga khalidwe la kudya, malingana ndi chibadwa. Mchitidwe wamakhalidwewa umagwirizanitsa kuchepa kwa kupezeka kwa D2R. Komanso, kuyang'ana kwa chilengedwe chinachake kumayambitsa D2R ndipo kumatsutsana ndi α1R mu striatum ndi medial prefrontal cortex, motero, ya nyama zovuta. Zofukufukuzi zimatsimikizira kuti ntchito ya jini ndi zochitika paziwonetsero zowonongeka ndikuthandizira kuganiza kuti kupezeka kwapadera kwa D2R ndi "chowopsa" cha chibadwa choyambitsa chilakolako chofuna kudya. Pomalizira, D2R upregulation ndi α1R pansiregulation mu statum ndi medial prefrontal cortex, motero, ndizo zowonjezera zokhazokha zomwe zimagwirizana ndi kusintha kwacho kuchokera ku zofuna zowonongeka.

Ndemanga: Patrono E, Di Segni M, Patella L, Andolina D, Valzania A, Latagliata EC, ndi al. (2015) Pamene Kufunafuna Chokoleti Kukukakamizidwa: Gene-Environment Interplay. PLoS ONE 10 (3): e0120191. yani: 10.1371 / journal.pone.0120191

Mkonzi Wophunzira: Henrik Oster, Yunivesite ya Lübeck, GERMANY

Zilandiridwa: August 7, 2014; Zavomerezedwa: February 4, 2015; Lofalitsidwa: March 17, 2015

Copyright: © 2015 Patrono et al. Ichi ndi nkhani yotseguka yolumikizidwa pansi pa mawu a Chilolezo cha Creative Commons Licribution, zomwe zimaloleza ntchito, kugawidwa, ndi kubwezeretsa mwachinthu chilichonse, kupatsa wolemba woyambirira ndi chitsimikizo

Kupezeka kwa Data: Deta zonse zoyenera zili mkati mwa pepala ndi ma fayilo Opatsirana Othandizira.

Ngongole: Ntchitoyi idathandizidwa ndi Ministero dell'Istruzione dell'Università e della Ricerca: Ateneo 2013 (C26A13L3PZ); MOTO 2010 (RBFR10RZ0N_001), Italy.

Zofuna zokakamiza: Olembawo adanena kuti palibe zotsutsana.

Introduction

Matenda odyera amayamba chifukwa cha chirengedwe ndi majini ndi zochitika zawo zovuta [1, 2]. Komabe, pali zochepa zofufuza za majini pazomwe anthu amadya nazo [2] ndi maphunziro a zinyama omwe asanthula zachilengedwe ndi zamoyo chifukwa chofuna kudya chakudya ndi kudya [3-6].

Zochitika zowopsya zimagwirizanitsa ndi ziwalo zomwe zimayambitsa matenda ndi kuonjezera chiopsezo cha zizoloŵezi zoledzera zomwe zimapangitsa kusintha kwa corticostriatal dopamine (DA) ndi zizindikiro za norepinephrine (NE) zomwe zimagwirizanitsa zolimbikitsana zomwe zimaperekedwa [7-9]. Umboni wopereka umboni umakhudza maulendo a dopamine mwa khalidwe lolimbikitsa [10-14] ndi D2Rs mu chidziwitso cha makhalidwe oponderezedwa, monga kuledzera [15-17].

Mphuno zosaoneka bwino zimapereka zitsanzo zabwino pophunzira kugwirizana pakati pa ma genetic ndi zachilengedwe [18]. C57Bl6 / J (C57) ndi DBA2 / J (DBA) mbewa zili pakati pa zovuta zosawerengeka zomwe zimapangidwira kafukufuku wokhudzana ndi maganizo a anthu chifukwa amadziwika bwino kusiyana ndi mayankho osiyanasiyana. Zomwe zimagwira ntchito komanso zomwe zimachitika m'maganizo a ubongo wawo wa ubongo, kuphatikizapo makhalidwe omwe amachititsa kuti zikhale zolimbikitsa, zakhala zikufufuzidwa kwambiri m'magawowa, motero zimapereka chidziwitso chofunikira pa momwe kuyankhulira kwa mitundu yosiyanasiyana ya zitsulo kumagwirizanako ndi chilengedwe chofanana kuti zikhale zosiyana siyana, zomwe zimayambitsa zosiyana (kapena zosiyana) zomwe zimachitika [19-23]. Makamaka, mbewa za C57 ndi DBA zimagwiritsidwa ntchito pofufuza kafukufuku wogwiritsira ntchito mankhwala osokoneza bongo chifukwa cha kusiyana kwawo kumagwiridwedwe ka mankhwala osokoneza bongo, monga kumwa mowa, kugwiritsira ntchito mankhwala osokoneza bongo, ndi opiates [7, 20, 21, 24-31]. Komanso, ponena za psychopathological endophenotypes [32-34], kusiyana pakati pa C57 ndi DBA mbewa mu D2R-zokhudzana ndi phenotypes zikuwoneka kuti zimadalira zochitika za jini-zachilengedwe [35-37].

Nkhumba za DBA sizigwirizana ndi zotsitsimula zowonjezera poyerekeza ndi mbewa za C57, boma limene likusonyezedwa ndi zochitika zopweteka zopweteka, kuwonjezeka kwa mankhwala osokoneza bongo mu DBA / 2 mbewa [24]. Choncho, timaganiza kuti kupuma kwapathengo kwapadera (caloric restriction) kumapangitsanso njira yofanana yomwe imakhudzira chakudya chokoma mu vuto la DBA. Ife tinayesa kudya mokakamiza pokhudzana ndi kuponderezedwa kwa chakudya chosavuta pansi pa zovuta [38], mu C57 ndi ma DBA. Kuletsedwa kwa zakudya mu makoswe kumawonekeratu kuti ndi zovuta zomwe zimayambitsa, pakati pa zotsatira zina, zimasintha mphamvu za ubongo ndi zomwe zimakhudza zomwe zimapangitsa kuti zikhale zolimbikitsa [8, 24, 39-42]. Komanso, zakhala zatsimikiziridwa kuti kulimbikitsidwa kwakukulu kwa mphotho zowonjezera kungayambitse kudya zakudya zogometsa kwambiri [38, 43, 44], ndipo kukakamiza mobwerezabwereza mphotho njira kudzera mu chakudya chokoma kwambiri kungayambitse kusinthasintha kwa ubongo zomwe zimapangitsa kuti khalidwe la kudya likhale lovuta kwambiri [45]. Zokhudza zachilengedwe zomwe zimakhudza matenda enaake, kupezeka kwa zakudya zonyenga ndizoonekera kwambiri [45] ndipo zawonetsedwa kuti zakudya zosiyana zimakhazikitsa zikhalidwe zosiyana za makhalidwe okhwimitsa [45, 46]. Chakudya chonse chokoma, chokoleti chawonetsedwa kuti chiri ndi zowonjezera zinyama [9, 47-49], ndipo ndi chakudya chomwe chimagwirizananso ndi malipoti a chilakolako cha chakudya mwa anthu. Motero, chilakolako cha chokoleti ndi chizolowezi cha chokoleti zakonzedwa mwa anthu [50].

Chifukwa chiletso cha caloric ndizochitikira zovuta [24], nyama zinayikidwa pa ndandanda yochepetsera chakudya [38], ndipo chifukwa chisanayambe kuwonetsa chakudya chokoma ndi chinthu chofunika kwambiri pa matenda ovutika [51], adatulutsanso chokoleti. Kudya magawo angapo a ma neural ndi kufunafuna mankhwala osokoneza bongo [52, 53]. Malinga ndi ntchito ya madokotala a DA m'zochita zothandizira mankhwala ndi zakudya [17, 51, 54, 55], tinayesa magulu a D1R ndi D2R subtype mu caudate putamen (CP), nucleus accumbens (NAc), ndi mapepala apakati a mpfc (mpFC) ndi alpha-1 adrenergic receptors (α1Rs) mu mpFC chifukwa prefrontal NE amafunika chakudya chokwanira -seeking [38] ndipo α1Rs imayanjanitsa zolimbikitsa ndi zotsatira zowonjezera mankhwala [56-58].

Tapeza kuti kukhudzana ndi chilengedwe kumapangitsa kuti munthu azikakamizidwa, monga momwe amadyera, malinga ndi chibadwa chake. Mchitidwe wamakhalidwewa unalumikizidwa kuti achepetse kupezeka kwa ma D2R. Kuonjezera apo, ma D2Rs omwe amalembedwa m'madera osiyanasiyana ndi omwe amalembedwa pansi pa α1Rs mu statum ndi pachipatala choyendetseramo ziweto.

Zofukufukuzi zimatsimikizira kuti ntchito ya jini ndi chilengedwe ndiyomwe ikuwonetseratu kuti kulimbikitsa kudya ndi kuthandizira kuganiza kuti kupezeka kwapadera kwa D2R ndi "khalidwe" loopsya la chikhalidwe cha khalidwe lokakamizidwa. Potero timapereka kuti D2R upregulation ndi α1R pansiregulation mu striatum ndi medial prefrontal cortex, motero, ndizo zowonjezera zomwe zimayenderana ndi kusintha kwacho kuchokera ku chizolowezi chodyera.

Zida ndi njira

nyama

Mwamuna C57BL / 6JIco ndi mbewa za DBA / 2J (Charles River, Como, Italy), masabata a 8-9 pa nthawi ya kuyesayesa, anali akugwiritsidwa ntchito ndi kusungidwa pa a12-h / 12-h kuwala / mdima (kuwala pakati pa 7 AM ndi 7 PM), monga momwe tafotokozera [9, 38]. Zomwe zinayesedwa pa lamulo la Italy (Decreto Legislativo no. 116, 1992) ndi European Communities Council Directive ya November 24, 1986 (86 / 609 / EEC) yomwe ikugwiritsa ntchito zinyama pofuna kufufuza. Zomwe zofufuza zaphunziroli zinavomerezedwa ndi komiti ya machitidwe a Utumiki wa Umoyo wa Italy ndipo motero anachitidwa pansi pa chilolezo / chivomerezo ID #: 10 / 2011-B, malinga ndi malamulo a Italy pankhani yogwiritsira ntchito nyama pofuna kufufuza (malamulo DL 116 / 92 ) ndi malangizo a NIH pankhani yosamalira nyama. Ndondomeko zowonjezereka zinatengedwa kuti kuchepetsa ululu ndi zovuta za nyama. Magulu otsogolera ankagonjera chokoleti chochepa (masiku 2); Magulu opanikizika adayikidwa pa chokoleti, "caloric restriction" ndi "mwachidule chisanadze" chokoleti musanayambe ndondomeko yotsutsa (onani pamwambapa kuti mudziwe zambiri).

Zotsatira zonse zinkachitika panthawi ya kuwala.

Ndondomeko Yopondereza Njira

Chida chothandizira kuyembekezera kuponderezedwa kale chinatchulidwa kale [38]. Chikho cha Plexiglas (3.8 masentimita m'mimba mwake) chinayikidwa m'chipinda chilichonse ndipo chinakonzedwa kuti chisamayende: 1 chikho chinali ndi 1 g ya chokoleti cha mkaka (Kraft) (Chocolate-Chamber, CC), ndipo chikho china chinali chopanda kanthu. , ESC).

Mwachidule, njirayi inali yotsatira: Kuyambira Tsiku 1 mpaka Tsiku 4 (maphunziro), mbewa (Kulamulira, magulu opsinjika maganizo pamtundu uliwonse) anaikidwa payekha pakhomo, ndipo zitseko zotseguka zinatsegulidwa kuti zilowetse m'zipinda ziwiri zonse momasuka ndipo fufuzani zipangizo zonse za maminiti a 30. Patsiku la 5, nyamazo zinkaoneka ngati zozizwitsa. Kupeza mkangano wothandizira (CS) (kuwala) -kugwirizanitsa gulu kunakhazikitsidwa mu zipangizo zosiyanasiyana, kuphatikizapo 15 × 15 × 20 cm chipinda cha Plexiglas chokhala ndi chida chakuda ndi choyera pamapiri a 2 (kusiyanitsa ndi zida zowonongeka) ndi galasi yosanjikizidwa ndi galasi komwe kudutsa kumeneku kunaperekedwa. Kuwala kunapangidwa ndi nyali ya halogen (10W, Lexman) pansi pa galasi pansi yomwe inayambika kwa 5, nthawi ya 20 nthawi iliyonse ya 100 sec; nthawi iliyonse, itatha kuwala kwa 19, mphindi ya 1-mA ya 0.15-mA inaperekedwa. Msonkhanowu wamsonkhanowu unapitilira kwa 10 min ndipo unatsatiridwa ndi mpumulo wa miniti ya 10, pambuyo pake gawo lina lofanana la 10 lophwanyidwa bwino linaperekedwa; ponseponse, mphuno zalandira 10 phazi loopsya zojambulidwa mu gawo la 30. Patsiku la 6-8, mbewa zinasiyidwa mosagwedezeka m'nyumba zawo. Patsiku la 9, kuponderezedwa kwa chokoleti choyesedwa kunayesedwa mu gawo loyesa (lomwe linapangidwira tsiku loyesa kuyerekezera), pomwe makoswe anali nawo chokoleti mu 1 ya zipinda za 2 zomwe chokoleti chinayikidwa panthawi ya maphunziro. Mu chipinda chokhala ndi chokoleti (CC), CS (kuwala) kunaperekedwa molingana ndi paradigm yothandizana ndi magetsi (kupatula nthawi ya mpumulo wa 10, yomwe inachotsedwa). Kuwala kunapangidwa ndi nyali ya halogen pansi pa galasi pansi yomwe idapangidwira nthawi ya 20-mphindi iliyonse ya 100. Gawoli lapitilira 20 min; Zonsezi, mbewa zalandira nthawi ya 10 20 mu gawo la 20.

Gawoli layeso linayamba ndi kuwala koyamba kwa 20. Nthaŵi yomwe inagwiritsidwa ntchito muzipinda zonse za 2 zinalembedwa patsikuli. Zayesero zonse zinachitidwa mu zipinda zowonongeka bwino zomwe zinayikidwa mwachindunji ndi nyali yoyimira (60 W). Kwa mayesero onse a khalidwe, deta inasonkhanitsidwa ndi kusanthuledwa pogwiritsira ntchito "EthoVision" (Noldus, The Netherlands), kayendedwe ka kanema kotsatira kanema. Pulogalamuyi inagwiritsidwa ntchito ndi pulogalamuyo kuti ipeze "nthawi yomwe inagwiritsidwa ntchito" (pamphindi) muzipinda, zomwe zimagwiritsidwa ntchito ngati deta yaikulu ya zokonda / zovuta zina mu gawo lililonse la zipangizo pa phunziro lililonse.

Magulu awiri a mbewa zachitsulo chilichonse anagwiritsidwa ntchito poyesera kuyesa: kuyendetsa (Control n = 6) ndi kupsinjika (Kupsinjika n = 8).

Njira Yoyesera

Ndondomeko yoyesera ikuwonetsedwa Chith. 1.

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Chizindikiro cha 1. Mndandanda wa Njira Yoyesera. (Onani Njira kuti mudziwe zambiri.)

http://dx.doi.org/10.1371/journal.pone.0120191.g001

Kuwonetseratu kale chokoleti

Nyama m'magulu opanikizika (Opsinjika C57 ndi Opsinjika DBA) adapezeka ndi chokoleti kwa masiku 7 mpaka 18 (kuyambira tsiku -XUMU kufikira tsiku -XUMUM, Chith. 1) masiku asanayambe ndondomeko yotsutsa. Nthanga zinali "mwachisawawa" tsiku ndi tsiku kwa maola a 4; Chokoleti cha mkaka ndi chakudya choyenera ad libitum. Patatha masiku awiri kutha kwa dongosolo lino (tsiku -XUMUM, Chith. 1), mbewa m'magulu opanikizika zinkalamulidwa ndi caloric restriction (chakudya choletsa, FR).

Kuletsa kwa Caloric

Nkhumba zinapatsidwa ntchito yokadyetsa zakudya: iwo adalandira chakudya ad libitum (Magulu Olamulira) kapena anali ndi regimen yoletsa zakudya (FR, magulu opsinjika). Mu chikhalidwe cha chikhalidwe cha caloric, chakudya chinaperekedwa kamodzi tsiku ndi tsiku (07.00 pm) mowonjezereka kusinthidwa pofuna kukopa imfa ya 15% ya kulemera kwake kwa thupi. Mu ad libitum chikhalidwe, chakudya chinaperekedwa kamodzi tsiku ndi tsiku (07.00 pm) m'zinthu zambiri zomwe zinasinthidwa kupitirira kupitirira tsiku lililonse [38].

Nyama zinayikidwa pa ndondomeko yoyenera ya FR [29] kwa masiku 10 (kuyambira tsiku -XUMU mpaka tsiku -XUMUM, Chith. 1), mpaka masiku a 6 isanayambe njira yothetsera mavuto (tsiku 1, Chith. 1). Masiku asanu ndi limodzi asanayambe maphunziro, nyamazo zinabwereranso ad libitum kudyetsa pofuna kuthetsa zotsatirapo zonse za kusowa kwa zakudya pakadutsa tsiku loyesera.

Mwachidule chisanafike pa chokoleti

Pofuna kuteteza cholakwika chilichonse chosadziwika bwino cha chokoleti m'magulu omwe sanagonjere chikhalidwe cha "chisanafikepo" chomwe chafotokozedwa pamwambapa (magulu Olamulira), onse olamulira ndi magulu opanikizika, adapeza chokoleti panthawi yomweyo ya masiku 2, masiku a 2 musanayambe kukakamizidwa kuti muyambe kukambirana ("mwachidule chisanachitike").

Kulemera kwa chokoleti ndi kulemera kwa nyama

Chokoleti cha chokoleti panthawi zosiyana siyana za ndondomeko yowonongeka (kusanayambe kufotokoza, kuphunzitsidwa, kuyesedwa) kunayesedwa, ndipo kulemera kwa nyama kunalembedwa. Manyowa anayezedwa: tsiku loyamba la kuyesa (musanayambe ndondomeko yoyesera), masiku ophunzirira, ndi tsiku la kuyesedwa koyesa.

Dopaminergic ndi noradrenergic receptors amafotokoza mu Mankhwala Oletsa ndi Opsinjika DBA

α1R, D1R ndi madokotala a D2R amasonyeza m'madera a ubongo a 3 [mpFC (α1R, D1R, D2R); NAc (D1R, D2R); ndipo CP (D1R, D2R)] inayesedwa ndi kumadzulo kumtunda kulamulira (Control DBA n = 6) ndi nyama zolimbitsa (Zopanikizika DBA n = 8), magulu omwewo omwe amagwiritsidwa ntchito poyesedwa.

Dopaminergic ndi noradrenergic receptor mawu mu naïve C57 ndi DBA mbewa

Baseline D1R, ndi madokotala a D2R omwe amawafotokozera mu mpFC, NAc, ndi CP komanso mzere woyamba α1R mu mpFC unayesedwa ndi zinyama zazinayi zonse [naïve C57 (n = 6) ndi naive DBA (n = 6)] kumadzulo pekani. Kuyesera kumeneku kunkachitidwa pa nyama zomwe sizinayanjidwe ndi zochitika zachilengedwe (chisanafike pa chokoleti, FR) kapena ndondomeko yowonongeka (magulu osadziwika) kuti ayesere kuganiza kuti ma D2 omwe amapezeka pamtunduwu ndi omwe amachititsa kuti pakhale chakudya chokwanira. -makhalidwe onga.

Kumadzulo kumadzulo

Nthangazi zinkaperekedwa ndi kutsekedwa, ndipo ubongo unachotsedwanso 1 h pambuyo poyesedwa, kupatulapo magulu omwewo. Mitundu yapamwamba, yowonongeka, ndi yowonongeka inagawanika ndikusungunuka ndi nayitrogeni yamadzi. Zizindikiro za mpFC, NAc, ndi CP zinapezedwa ku magawo a ubongo wouma monga momwe amafotokozera [59] (S1 Mkuyu.) ndi kusungidwa mu madzi azitrogeni mpaka tsiku la kuyesa. Chitsanzo chilichonse cha mankhwalawa chinapangidwa ndi 4 ° C m'thumba la lysis (20 mM Tris (pH 7.4), 1 mM EDTA, 1 mM EGTA, 1% Triton X-100) ndi protease inhibitor cocktail (Sigma-Aldrich, St. Louis, MO , USA).

Mphuno ya minofu inali yaikulu pa 12,000 g pa 4 ° C kwa 30 min. Wopatsa mphamvuyo ankachitidwa mofanana ndi chigawo cha minofu. Pomalizira, Wopambana ndi mphamvuyo adachotsedwa ndikusungidwa ku 80 ° C.

Mapuloteni analiyeso ndi Bradford assay (BioRad Laboratories, Hercules, CA, USA).

MpFC, NAc, ndi CP zinafufuzidwa pogwiritsa ntchito, 60 ug, 30 ug, ndi 30 ug, motsatira chitsanzo cha puloteni iliyonse. % bromophenol buluu) ndi kutentha kwa 0.5 min pa 30 ° C. Mapuloteni analekanitsidwa ndi electrophoresis pa 10% acrylamide / bisacrylamide gels ndipo anasamutsa electrophoretically ku nitrocellulose nembanemba, zomwe zinatsekedwa kwa 0.6 h pa 0.012 ° C-5 ° C mu mchere wotchedwa Tris-buffered (mM: 95 NaCl ndi 10 Tris-HCl , pH 1), yomwe ili ndi 22% Tween 25 (TBS-T) ndi 137% mkaka wa mafuta ochepa.

Mankhwalawa ankagwiritsidwa ntchito ndi ma antibodies oyambirira [kalulu anti-dopamine D1 (Immunological Sciences) ndi kalulu anti-dopamine D2 receptor (Immunological Sciences), 1 diluted: 800 mu TBS-T ndi 5% mafuta ochepa, kapena kalulu anti-alpha1- adrenergic receptor (mkomber), 1 kuchepetsedwa: 400 ndi 1% mkaka wochepa mafuta usiku umodzi pa 4 ° C. Pambuyo kutsukidwa kwambiri mu TBS-T, ma membrane adakonzedwa chifukwa cha 1 h firiji (22 ° C-25 ° C) ndi ma antibodies omwe amagwirizana ndi HRP (anti-rabbit IgG omwe adasankhidwa 1: 8000 (immunological sciences) mu TBS- T ndi 5% mkaka wa mafuta ochepa) ndipo unapangidwa ndi ECL-R (Amersham). Zizindikirozo zinali zojambulidwa ndi digitally ndipo zimagwiritsidwa ntchito pulogalamu yamakono yajambula (imagej 64), yovomerezeka kwa tubulin.

Statistics

Kuyesedwa Kuyesedwa kuyesa.

Chifukwa cha kuyesedwa koyeso, kufufuza kwa chiwerengero kunkachitidwa kwa nthawi (sec) yomwe idakhala pakatikati (CT), m'chipinda chokhala ndi chokoleti (CC) komanso m'chipinda chopanda kanthu (ES-C) panthawi ya maphunziro (onse tanthauzo la masiku a 4 a maphunziro) komanso pa tsiku la kuyesedwa koyeso. Detayi inafotokozedwa pogwiritsira ntchito mobwerezabwereza ANOVA, ndi 2 pakati pa magulu a magulu (zovuta, maselo a 2: C57, DBA; chithandizo, miyeso ya 2: Control, Stressed) ndi 1 mkati mwa gulu (chipinda, ma 3: CT, CC , ESC). Nthawi yochuluka mu CC ndi magulu a ES-C anafanizidwa pogwiritsa ntchito njira zobwerezabwereza ANOVA mkati mwa gulu lirilonse. Kusiyanitsa pakati pa magulu kunkayesedwa ngati kuli koyenera njira imodzi.

Chokoleti chodyera ndi kulemera.

Chokoleti cha phokoso panthawi yophunzitsidwa (kutanthauza kuti masiku onse a 4) komanso nthawi yomwe akuyesa kuyesedwa tsiku ndi tsiku ankayang'aniridwa ndi ANOVA (mavuto, ma 2: C57, DBA; chithandizo, miyezo ya 2: Control, Stressed). Chokoleti cha chokoleti pa nthawi yoyamba kuwonetseredwa ndi njira imodzi ya ANOVA (mavuto: Kupsinjika C57, Stressed DBA). Kulemera kwa nyama kunalembedwanso pa tsiku loyambirira la kuyesa (musanayese ndondomeko ya kuyesera), panthawi yophunzitsira, komanso pa tsiku loyesedwa. Detayi inafufuzidwa ndi ANOVA njira ziwiri (mavuto, misinkhu ya 2: C57, DBA; chithandizo, miyezo ya 2: Control, Stressed).

Dopaminergic ndi noradrenergic receptors amafotokoza mu Mankhwala Oletsa ndi Opsinjika DBA.

Mawu a D1R ndi a D2R mu mpFC, NAc, ndi CP ndi D1R, D2R, ndi ma α1R pa Dressed Press DBA ndi Control DBA zinagwiritsidwa ntchito ndi njira imodzi ya ANOVA (mankhwala, ziwerengero za 2: Control DBA, Stressed DBA).

Dopaminergic ndi noradrenergic receptors amasonyeza kuti ali ndi C57 ndi ma DBA.

Mawu a D1R ndi a D2R mu mpFC, NAc, ndi CP ndi D1R, D2R, ndi ma α1R pazinthu za C57 ndi DBA (naive C57, ndi DBA) zimagwiritsidwa ntchito ndi njira imodzi ya ANOVA (mavuto, zigawo za 2: C57, DBA) .

Results

Kuyesa kuyesedwa kuyesa: Kufunafuna chakudya pa makoswe a DBA opanikizika

Pofuna kudziwa momwe zinthu zimayendera pakati pa majeremusi ndi zochitika zachilengedwe zomwe zimawonetseratu chizoloŵezi chodya kudya, nthawi yomwe amagwiritsidwa ntchito mu CC ndi ES-C pazigawo zosiyana (kuphunzitsidwa ndi kuyesa) ndondomeko yowonongeka yomwe ikuwonetsedwa ndi magulu opanikizika ndi olamulira Mitundu yonseyi inayesedwa (Control C57, Control DBA, Stressed C57, Stressed DBA).

Pakusanthula gawoli, tawona zovuta x chithandizo x kulumikizana kwa chipinda (F (1,72) = 6.52; p <0.001). Kuyerekeza nthawi yomwe amakhala mu CC ndi ES-C pagulu lirilonse kukuwonetsa kuti magulu okhawo a Control C57 ndi Stress DBA amakonda CC motsutsana ndi ES-C panthawi yophunzitsira (Control C57: F (1,10) = 6.32; p <0.05; Kupsinjika DBA: F (1,14) = 15.60; p <0.05) (Chith. 2), kuthera nthawi yambiri mu CC kusiyana ndi ES-C.

Chizindikiro cha 2. Maphunziro Oletsedwa Kuponderezedwa mu C57 ndi DBA mbewa.

Nthawi yogwiritsidwa ntchito (sec ± SE) m'chipinda chokhala ndi chokoleti (CC) komanso mchipinda chotetezeka chopanda kanthu (ES-C) panthawi yophunzitsidwa ndi magulu a Control C57 / DBA (n = 6 pagulu lirilonse) (A) ndi Kupanikizika C57 / Makoswe a DBA (n = 8 pagulu lirilonse) (B). * p <0.05 poyerekeza ndi ES-C.

http://dx.doi.org/10.1371/journal.pone.0120191.g002

Ponena za zotsatira za mayeso, tawona kulumikizana kwakukulu pakati pamavuto, chithandizo ndi chipinda (F (1,72) = 6.0; p <0.001). Mitundu iwiriyi idawonetsa mitundu yosiyanasiyana ya nthawi yogwiritsidwa ntchito mu CC ndi ES-C. Magulu onse olamulira (C57, DBA) adakhala nthawi yayitali ku ES-C poyerekeza ndi chipinda chomwe chinali ndi chokoleti (CC), momwe panali zolimbikitsira (CS) (C57: F (1,10) = 6.04; p <0.05; DBA: F (1,10) = 12.32; p <0.01), kuwonetsa kuponderezedwa kofunafuna chokoleti pakuwonetsa CS. Mosiyana ndi izi, pomwe mbewa Zapanikizika za C57 sizinawonetse chidwi chilichonse kapena kubweza chipinda chilichonse (F (1,14) = .381; ns), nyama Zapanikizika za DBA zimathera nthawi yambiri mu CC poyerekeza ndi ES-C, (F ( 1,14) = 7.38; p <0.05) (Chith. 3), motero amasonyeza khalidwe lofunafuna chakudya ngakhale kuti zingakhale zovuta.

 

Chizindikiro cha 3. Mayeso Otsutsa Kugonjetsedwa mu C57 ndi DBA mbewa.

Nthawi yogwiritsidwa ntchito (sec ± SE) m'chipinda chokhala ndi chokoleti (CC) komanso mchipinda chotetezeka chopanda kanthu (ES-C) panthawi yoyeserera koyeserera kwamagulu a Control C57 / DBA (n = 6 pagulu lirilonse) (A) ndi Kupanikizika C57 / Mbewa za DBA (n = 8 pagulu lirilonse) (B). * p <0.05; ** p <0.01 poyerekeza ndi CC.

http://dx.doi.org/10.1371/journal.pone.0120191.g003

Zotsatira izi zikuwonetsa kuti kuyang'ana kwa chilengedwe chathu chofuna chokoleti chosasamalidwa ndi zizindikiro, kulongolera khalidwe lofunafuna chakudya mofunafuna mwachangu mu mbewa za DBA (Chith. 3).

Chokoleti chodyera ndi kulemera

Kuti muone ngati chakudya cha chokoleti chawonetsedwa ndi magulu Olamulira ndi Opanikizika a magulu onse awiri (Control C57, Control DBA, Stressed C57, Stressed DBA), kugwiritsira ntchito chokoleti kunayesedwa pazigawo zosiyanasiyana (chisanafike, kuphunzitsidwa, kuyeza) njira yothandizira.

Ponena za kudya chokoleti pa nthawi yoyamba, panalibe kusiyana kwakukulu pakati pa makina a C57 ndi Opsinjika DBA (F (1,14) = 0.83; ns) (Chith. 4).

 

Chizindikiro cha 4. Chokoleti chodyera mu C57 / DBA Control ndi magulu opanikizika.

Kudya chokoleti mu C57 / DBA Control (n = 6 pagulu lirilonse) ndi Kupanikizika (n = 8 pagulu lirilonse) nyama zolembedwa asanawonetsedwe (A), maphunziro (B), ndi mayeso (C). Zambiri zimafotokozedwa ngati ma gramu (masiku onse ± SE a A ndi B). * p <0.05; *** p <0.001 poyerekeza ndi gulu lolamulira la zovuta zomwezo. ### p <0.001 poyerekeza ndi gulu lomwelo la mtundu winawo.

http://dx.doi.org/10.1371/journal.pone.0120191.g004

Ponena za kudya chokoleti panthawi yophunzitsira, panali kulumikizana kwakukulu pakati pamavuto ndi chithandizo F (1,24) = 20.10; p <0.001). Mwa kuyerekezera kwapakati pa gulu, tawona kusiyana kwakukulu pakati pa Control DBA ndi Stress DBA ((F (1,12) = 46.17; p <0.001), Control C57 motsutsana ndi Kupanikizika C57 ((F (1,12) = 24.25 ; p <0.001), ndi Kupanikizika C57 motsutsana ndi mbewa za DBA ((F (1,14) = 27.52; p <0.001) (Chith. 4). Nyama za DBA zolemetsa zinkasonyeza kwambiri kudya chokoleti poyerekeza ndi magulu ena onse.

Kufufuza kwa kudya chokoleti patsiku loyesa kunawonetsa kulumikizana kwakukulu kwa chithandizo cha mankhwala (F (1,24) = 21.48; p <0.005). Kuyerekeza kwapakati pa gulu kunawonetsa kusiyana kwakukulu pakati pa kuwongolera ndi Kupanikizika DBA ((F (1,12) = 38.49; p <0.001), Control and Stress C57 ((F (1,12) = 7.90; p <0.05) and Wapanikizika C57 ndi mbewa Zapanikizika za DBA ((F (1,14) = 33.32; p <0.001) (Chith. 4). Nyama za DBA zolemetsa zinkakhala ndi chokoleti chokwanira kwambiri poyerekeza ndi magulu ena onse, kutanthauza chokwanira chokoleti chokongoletsera, mogwirizana ndi chilakolako chofuna kuyesedwa pokhapokha kuyesedwa.

Pomaliza, potsata zolemera, kusanthula kwa chiŵerengero kunasonyeza kuti kulemera kwa nyama sikunali kusiyana kwambiri pakati pa magulu pa tsiku loyamba la kuyesa (musanayambe njira yoyesera (F (1,24) = 2.22; ns), pa gawo la maphunziro (F ( 1,24) = 2.97; ns) ndi tsiku lachiyeso choyesa (F (1,24) = 0.58; ns) (Chith. 5).

Chizindikiro cha 5. Kulemera kwa nyama.

Kulemera kwa chiwerengero (n = 6 pa gulu lililonse) ndi kupsinjika (n = 8 kwa gulu lirilonse) Magulu a C57 / DBA amayesedwa musanayambe kusokoneza (A), pa tsiku loyamba lophunzirira (B) ndi tsiku loyesera (C). Deta imayesedwa ngati gram ± SE.

http://dx.doi.org/10.1371/journal.pone.0120191.g005

Zonsezi, deta yathu ikuwonetseratu kugwirizana kwakukulu pakati pa ma genetic ndi zochitika za chilengedwe poyesa kudya zakudya zopanda malire, mogwirizana ndi maphunziro apitalo omwe anafotokoza ntchito yovuta pazifukwa zina zovuta kudya [3-5, 38].

Dopaminergic ndi noradrenergic receptor expression mu mpFC, NAc, ndi CP ya Stressed DBA vs Control DBA mbewa

Kuti muone ngati dopaminergic ndi noradrenergic receptors zinyama, zomwe zimadandaula, monga "kudya" (Dressed stress DBA), zizindikiro za α1R, D1R ndi D2R mu mpFC komanso D1R ndi D2R ku NAC ndi CP zinayesedwa muzopsinjika. DBA makoswe (Chith. 6).

 

Chizindikiro cha 6. Mafotokozedwe a DA ndi a Receptors mu vuto la DBA.

Kufotokozera kwa D1R ndi D2R mu CP ndi NAc (A) ndi D1R, D2R ndi α1 mu mpFC (B) ya Stress DBA (n = 8) ndi Control group (n = 6). * p <0.05; ** p <0.01 poyerekeza ndi gulu lolamulira. Zambiri zimawonetsedwa ngati chiyerekezo ± SE.

http://dx.doi.org/10.1371/journal.pone.0120191.g006

D2Rs adasinthidwa mu NAc (F (1,12) = 5.58; p <0.05) ndi CP (F (1,12) = 10.74; p <0.01) ya Stress DBA poyerekeza ndi mbewa za Control DBA (Chith. 6), kuwonetsa kusankhidwa kwa ma striatal D2 receptors mu nyama zomwe zimawonetsa kukakamizidwa ngati kudya. Palibe phindu lililonse lomwe lidawonekera kwa olandila D1. α1Rs inali yotsika mu mpFC ya Stress DBA group poyerekeza ndi Control DBA mbewa (F (1,12) = 7.27; p <0.05) (Chith. 6). Palibe zotsatira zowonongeka kwa oprontal D1R kapena D2R kulandira mauthenga.

Dopaminergic ndi noradrenergic receptor expression mu mpFC, NAc, ndi CP ya naïve DBA motsutsana ndi naive C57 mbewa

Pofuna kufufuza zowonjezera maulendo a α1R, D1R ndi D2R, mawu a α1R, D1R ndi D2R mu mpFC komanso D1R ndi D2R ku NAc ndi CP zinayesedwa m'magulu awiri a nyama zosadziwika za mitundu yonse iwiri ( naïve C57 ndi naïve DBA) (Chith. 7).

 

Chizindikiro cha 7. Mafotokozedwe a DA ndi a RE Ovomerezeka mu naïve C57 ndi DBA nyama.

Kufotokozera kwa D1R ndi D2R mu CP ndi NAc (A) ndi D1R, D2R, ndi α1 mu mpFC (B) yamagulu a naïve C57 / DBA (n = 6 pagulu lirilonse). ** p <0.01 poyerekeza ndi gulu la naïve la zovuta zina. Zambiri zimawonetsedwa ngati chiyerekezo ± SE.

http://dx.doi.org/10.1371/journal.pone.0120191.g007

Tidawona kupezeka kotsika kwa D2R mu NAc ya naïve DBA motsutsana ndi naïve mbewa za C57 (F (1,10) = 11.80; p <0.01). Palibe kusiyana kwakukulu komwe kunawoneka mu D1R, D2R, kapena α1R m'malo ena aubongo (Chith. 7). Zotsatira izi, zogwirizana ndi deta yapitayo [4, 54, 60, 61], zithandizira lingaliro lakuti kuchepa kwa D2R ndi "chiopsezo" chotengera chibadwa chomwe chimayambitsa chiopsezo cha kudya zakudya zosafunika.

Kukambirana

Tinayesa kudya chakudya chokwanira pogwiritsa ntchito njira yothetsa chakudya / chakudya chokwanira pakagwa mavuto [38] mu C57 ndi ma DBA. Kuwonetsera kwa chilengedwe kumapangidwira-monga kudya kudya, malingana ndi chibadwa. Komanso, chitsanzo cha khalidweli chikuwoneka kuti chikugwirizana ndi kupezeka kwapang'ono kwakumvera kwa D2 receptors. Tinawonanso D2R upregulation ndi α1R downregulation mu striatum ndi mpFC, motero - yankho labwino lokhazikika lomwe likufanana ndi kusintha kwacho kuchoka ku chizoloŵezi chokhala ngati khalidwe lodya.

Zomwe timayesa zimasonyeza kuti kugwirizana pakati pa chokoleti choyambirira chisanachitike ndi choletsa cha caloric kumapangitsa kuti chokoleti chofunafuna chokoleti chikhale chosapereka chilango, kusintha khalidwe lofunafuna chakudya m'kukakamiza monga kudya. Chowoneka, khalidwe ili limadalira kwambiri genotype. Zotsatira zowononga zowonetsera ziwonetsero kuti nyama zokhazokha za DBA zinkasonyeza khalidwe lofunafuna zakudya, ngakhale zingakhale zovuta.

Zotsatirazi sizingakhale zosiyana ndi kusokonezeka maganizo pakati pa makina a C57 ndi DBA, monga momwe akuwonetsedwera ndi kuyesa komweko (onani Njira za S1 ndi S2 Mkuyu.) ndipo monga momwe amafotokozedwera ndi magulu ena [62]. Kuwonjezera pamenepo, khalidwe lofunafuna chakudya linayamba, muzinthu zolimbitsa DBA, zomwe zimagwirizana ndi khalidwe la kudya monga momwe zimawonetsedwa ndi gulu la chokoleti. Ngakhale kudya zakudya zambiri zowonjezera kungasonyeze kuwonjezereka kwa chakudya, kuchita zimenezi ngakhale pangozi zowononga, monga kulekerera kulandira chilango, kukuwonetseratu zifukwa zowonjezera chakudya (kukakamizidwa) [5].

Choncho, pamene DBA mbewa zimakhala "chitsanzo chabwino" chotsutsa mankhwala osokoneza bongo [24] komanso matenda okhudzana ndi zakudya m'moyo wabwino (zotsatira zake), zimakhala zovuta kwambiri kwa mankhwala [24] ndi zotsatira zokhudzana ndi zakudya pamene zimayesedwa ndi zovuta zina zachilengedwe. Kuwonjezera apo, kuyesa koyambirira kumasonyeza kuti kuwonetsedwa kwa chinthu chimodzi chokha (kusanayambe kutsogolo kwa chokoleti kapena caloric chiletso, mosiyana) sichimapangitsa kuti phenotype (Njira za S1 ndi S3 Mkuyu.). Motero, zotsatira zokhazokha za chilengedwe (kusanunkhira kwa chokoleti ndi chiletso cha caloric) zimapangitsa kudya kudya kutsutsana ndi zizindikiro za chilango (kulakwitsa-monga khalidwe la kudya). Chotsatira ichi chikugwirizana ndi umboni umene umasonyeza kuti kukhalapo kosangalatsa [46, 51], kuvutika maganizo [1, 63-65], ndi mgwirizano wothandizana pakati pa kupanikizika ndi kulekanitsidwa kwa kalori ndizofunikira kwambiri zomwe zimayambitsa vuto la kudya kwa anthu ndi zinyama [65-67].

Kusintha kuchoka ku chizoloŵezi chololedwa-monga chizolowezi chodya chomwe chikuwonetsedwa ndi makoswe a DBA opanikizika akuwoneka kuti akugwirizana ndi kusintha kwa dopaminergic ndi noradrenergic receptors kufotokoza pFC-NAc-CP. Ndipotu, mbewa zopanikizika za DBA, zomwe zimasonyeza khalidwe lopanda kudya (monga kusonyeza kuti palibe chifukwa chotsitsimula), zinawonetsa kuti D2R iwonongeke mu NAC ndi CP komanso kuwonongeka kwa α-1AR mu mpFC, poyerekeza ndi DBA yolamulira. Kuonetsetsa kuti zotsatira zowonongeka zingapangidwe ndi zakudya zosiyanasiyana za chokoleti pamsonkhano woyesedwa ndi Control and Stressed DBA, kuyesa kwina kunayesedwa. Zomwe anayesera ndi ndondomekozo zinali monga momwe anafotokozera DBA Yopanikizika ndi Yopanikizika, koma mauthenga obvomerezedwa anachitidwa pa ubongo kuchotsedwa kwa mbewa popanda chokoleti chogwiritsa ntchito (pa tsiku loyesera). Zotsatira za kuyesera uku (Njira za S1 ndi S4 Mkuyu.), sichikutsutsa kuti kusinthidwa kwa D2R ku NAC ndi CP komanso kuwonongeka kwa α-1AR mu mpFC yosonyezedwa ndi Stressed DBA kungapangidwe chokoleti.

Zotsatira zomwe zimachitika mu NAC ndi CP za mavenda opsinjika a DBA sizilola kuti tiwone zotsatira za kufalitsa kwa DA - mwachitsanzo, ngati kusintha kumawonjezera dopaminergic tone, kufuna kudziwa zambiri zokhudza mawonekedwe a D2 mawonekedwe - mwachitsanzo, chiwerengero cha 2 Mitundu yambiri ya mRNA, D2R-long (D2L) ndi D2R -fupi (D2S) - m'madera a 2, chifukwa chiwerengero cha isoforms mu striatum chimakhudza neural ndi khalidwe zotsatira za D1R ndi D2 / 3R co-activation [68-70]. Timaganiza kuti kuwonjezeka kwa mapepala a postsynaptic ndi kukwera kwa dopamine kutumiza kumalimbikitsa ndi kulimbitsa khalidwe lofuna chakudya [11]. Komabe, kufufuza zambiri kufunikira kumafufuza kuti ndi mtundu wanji wa D2R womwe umakhudzidwa ndi ndondomeko yathu yoyesera.

Kuwonjezeka kwa mawu a D2R otha msinkhu m'magulu opanikizika a DBA akuwoneka kuti akusiyana ndi lingaliro lomwe likusonyeza kuti kugwetsedwa kwa D2R yopweteka ndi njira yothandizira yowonongeka kwa chakudya chokoma. Komabe, kuchepetsa kugwiritsidwa ntchito kwa D2R yowonongeka kwawonetsedwa kuti ndi njira yowonjezera yowonjezera chakudya chokwanira ndi kuledzera kwa anthu ndi zinyama [4, 44, 60, 71-75] komanso kachilombo koyambitsa matenda omwe amachititsa chiopsezo kuti asadye [4, 54, 60, 61, 75]. Kuwonetsera kwakukulu kwa D2R zomwe taziwona mu phunziroli zikhoza kukhala zotsatira zokhudzana ndi chilengedwe (zomwe zisanachitike, kutsekemera kwa kalori) zomwe zimayambitsa matenda enaake omwe amagawana ndi mavuto ena ovuta kudya. Chotsutsana pa nkhaniyi kawirikawiri chimaona kuti kunenepa kwambiri ndi matenda oledzeretsa, zomwe zimakhala zovuta kwambiri (monga kuwonjezeka kwa kulemera, magawo odyetserako zakudya, kupititsa patsogolo chakudya chokhala ndi mafuta ambiri) kukhala-osati chizolowezi chodya pa se, monga momwe tawerengedwera mu phunziro lino.

Kuwonjezeka kwa umboni wotsutsana ndi D1R ndi D2R omwe amawombera phindu lopindulitsa lomwe limatsimikiza mtima kufuna khama kuti lipeze mphotho yosankhidwa, motero zimakhudza khalidwe lolimbikitsa [10-14]. Komanso, zolinga zabwino-zolinga zoyendetsedwa ndi zolimbikitsa zikuwoneka zikugwirizana ndi maulendo apamwamba a D2R mu striatum [12, 76-79]. Phunziro lathu likuwonetsa kuti kuyankhula koopsa kwa D2R kumagwirizananso ndi matenda a phenotype, omwe amachititsa kuti lingaliro la D2R likhale lovomerezeka ndi neural correlate ya zolinga zoyenera-zoyenera kutsogozedwa ndi cholinga.

Chotsatira china chachikulu chinali kupezeka kwapang'ono kwa D2R mu NAc ya naïve DBA ndi yosavuta C57 mbewa. Monga tafotokozera, kuchepa kwa D2R kufotokozedwa kuti ndi chiwopsezo cha chibadwa cha chiopsezo cha kudya zakudya zopatsa mphamvu [4, 54, 60, 61, 75]. Ndiponso, kuchepa kwa D2 / D3 dopaminergic receptor kupezeka mu ventral striatum yapangidwa kuti apangitse kuchulukitsa kwowonjezereka kuwonjezereka kudya kwa mankhwala ndi kugwirizana ndi kukhudzidwa kwakukulu [16, 79, 80]. Kuwonjezera pamenepo, mbewa za DBA / 2 zakhala zikudzikweza kwambiri [81, 82]. Choncho, timalingalira kuti kupezeka kwa D2R kochepa komwe kumawoneka m'magulu a chipani cha DBA osadziwika bwino chifukwa cha chizoloŵezi chosiyana cha kudya zakudya zopanda chilema pamtundu wina wa chilengedwe, kuchepetsa caloriki ndi kupezeka kwa zakudya zogwira mtima zomwe zimakhudza chitukuko ndi kuwonetsa kwa matenda odwala [4, 46, 64, 83, 84].

Tinawona kuchepa kwa mawu a prefrontal α1R mu mbewa za DBA zolimbana ndi Control Control. Ngakhale kupititsa patsogolo kwa HIV kwapadera kwafunikiranso kuti chichitidwe chokhudzana ndi zakudya [9] ndipo ngakhale NE neurons (makamaka kupyolera mu α1Rs) amatsutsana ndi kuonjezera zotsatira za mankhwala osokoneza bongo [57, 58, 85], palibe kafukufuku amene wasanthula kuyanjana kwa mapulogalamu a prefrontal noradrenergic pamakakamizidwa-monga khalidwe la kudya. Zotsatira zathu zikulitsa zotsatira zapambuyo pa ntchito ya prefrontal NE kupititsa patsogolo muzochita zokhudzana ndi chakudya, kutanthauza kuti zovomerezekazo zimayambitsa zofuna zowonjezera zokhudzana ndi kudya koyenera. Kusokonezeka kwa α1R mu mpFC kungakhale njira yosinthira yomwe ikugwirizana ndi kusunthira kuchokera kuchitsimikizo choyendetsa chizoloŵezi choyendetsa, chotsogoleredwa ndi ntchito yowopsya ya cortex ndi ntchito yaikulu ya striatum. Komabe, kufufuza kwina kuli kofunika kuti tifufuze mfundoyi.

The hypothalamus ndi imodzi mwa malo ofunika kwambiri a ubongo olamulira chakudya [86-88]. Komabe, maulendo osiyanasiyana a ubongo, omwe sali okhudza njala ndi satiety, apatsidwa kuti azitha kudya zakudya [60, 89]. Kuwonjezera apo, mazira ena ambiri a mphuno ndi mahomoni, kuphatikizapo DA, NE, acetylcholine, glutamate, cannabinoids, opiods ndi serotonine, komanso tizilombo toyambitsa matenda omwe amagwira ntchito kunyumbaostatic kudya zakudya, monga orexin, leptin ndi ghrelin, zimakhudzidwa ndi zotsatira za chakudya [60, 90-92]. Choncho, malamulo okhudzana ndi kudya kwa hypothalamus akuwoneka kuti akugwirizana ndi maulendo osiyanasiyana a neural omwe amapindula ndi zosangalatsa zomwe zimadya chakudya [60], monga preortal-accumbal system. Tiyenera kudziwa kuti mbewa za C57 ndi DBA zimawonetsa machitidwe osiyanasiyana komanso magwiridwe antchito amachitidwe aubongo wawo awunikidwa mozama pamatenda awa [19, 23], motero kumatanthauza kusiyanitsa, kuponderezana, kulamula, kuyang'anira, komanso kuyang'anira maulendo.

Njira yokhazikika yomwe ikuphatikizidwa pokonza zokhutiritsa ndi zokondweretsa mbali za chakudya (ndi mankhwala) ndizozungulira dera la mphotho ya dopaminergic [45, 51, 60]. Kukhulupiliridwa mobwerezabwereza kwa madalitso a DA kumakhulupirira kuti kumayambitsa matenda a neurobiological m'madera osiyanasiyana, motero kufunafuna khalidwe "kukakamiza" ndipo kumayambitsa kusala kudya (kapena mankhwala)51, 60].

Zakhala zikugwiridwa kuti pansi pazifukwa zosiyanasiyana zofikira, zowonjezereka zowonjezera zakudya zowonongeka zimatha kuyendetsa kusintha kwa khalidwe mwa kusintha kwa njira zamaganizo m'madera a ubongo okhudzana ndi chilimbikitso, kuphunzira, kuzindikira, ndi kupanga chisankho chomwe chimasonyeza kusintha komwe kunayambitsidwa ndi kugwiritsa ntchito mankhwala osokoneza bongo [83, 93-99]. Makamaka, kusintha kwa mphotho, zolimbikitsa, kukumbukira, ndi maulendo oyendetsa omwe akutsatiridwa mobwerezabwereza ndi chakudya chokoma ndizofanana ndi kusintha komwe kunachitika pambuyo powonetsa mankhwala mobwerezabwereza [60, 95]. Kwa anthu omwe ali pachiopsezo cha kusintha kumeneku, kudya chakudya chokwanira (kapena mankhwala osokoneza bongo) kungasokoneze mgwirizano pakati pa zolinga, mphoto, kuphunzira, ndi maulendo oyendetsa bwino, motero kuonjezera kuwonjezereka kwa chakudya chokoma (kapena mankhwala) ndikufooketsa maulendo oyendetsa [51, 60].

Malingaliro awa ndi zotsatira za phunziro lakale, lingathe kufotokoza kuti kusuntha kuchoka ku khalidwe lolimbikitsana ndi chizoloŵezi chodya chodziwika chomwe chili m'magulu a DBA angagwirizane ndi kusiyana pakati pa chibadwa cha majeremusi (kuchepa kwa D2 receptors kupeza mu phunziro ili komanso Kusiyanasiyana kwa magulu ena a ubongo ndi mahomoni omwe amaphatikizidwa m'madera okhudza ubongo) komanso kuwonetseredwa ndi zachilengedwe zomwe zimapangitsa kuti D2R upregulation ndi α1R pansiregulation mu striatum ndi mpFC, zithe kutsogolera pakati pa maulendo omwe amalimbikitsa khalidwe maulendo omwe amaletsa ndi kulepheretsa mayankho omwe alipo kale [60, 95].

Mawuwo

Pali zochepa zofufuza pa machitidwe a geni-chilengedwe mu mavuto a anthu odya [2]. Chitsanzo cha zinyama zomwe timakonzekera pano chikhonza kugwiritsidwa ntchito kumvetsetsa momwe chilengedwe chimagwirizanirana ndi zofunikira za chibadwa ndi zokhudzana ndi zinthu zokhudzana ndi matenda omwe amachititsa kuti anthu adziwe ngati kulimbikitsana, komanso kuti apereke chidziwitso chatsopano cha mankhwala osokoneza bongo.

Kuthandiza Information

S1_Fig.tif

https://s3-eu-west-1.amazonaws.com/ppreviews-plos-725668748/1951833/preview.jpg

 

chithgawo

 

1 / 5

Malo omwe amaimira anthu oyendetsa nkhumba (preFrontal Cortex) (mpFC) (A), Nucleus Acumbens (NAc) ndi Caudate-Putamen (CP) (B).

S1 Mkuyu. Kusintha malo.

Malo omwe amaimira anthu oyendetsa nkhumba (preFrontal Cortex) (mpFC) (A), Nucleus Acumbens (NAc) ndi Caudate-Putamen (CP) (B).

onetsani: 10.1371 / journal.pone.0120191.s001

(TIFF)

S2 Mkuyu. Kusokonezeka maganizo kumakhala ku C57 ndi DBA mbewa.

Kusokoneza mphamvu m'thupi la C57 ndi DBA (Njira S1). Kutanthauza (μA ± SE) chodabwitsa chomwe chimapezeka muzilombo za C57 ndi DBA.

onetsani: 10.1371 / journal.pone.0120191.s002

(TIFF)

S3 Mkuyu. Mayeso Oletsa Kuthetsa Mphindi DBA.

Nthawi yogwiritsidwa ntchito (sec ± SE) m'chipinda chokhala ndi chokoleti (CC) chipinda chopanda kanthu (ES-C) Panthawi Yoponderezedwa Poyesedwa ndi DBA chisanafike poyera ndi DBA Zogwiritsidwa Ntchito Zakudya.

onetsani: 10.1371 / journal.pone.0120191.s003

(TIFF)

S4 Mkuyu. Kufotokozera za DA ndi O Receptors m'magulu a DBA.

Kufotokozera kwa ma D2 receptors mu CP ndi NAc komanso α1 mu mpFC ya Stress and Control DBA mbewa (n = 6 pagulu lirilonse). * p <0.05 poyerekeza ndi gulu lowongolera. Zambiri zimawonetsedwa ngati chiyerekezo ± SE.

onetsani: 10.1371 / journal.pone.0120191.s004

(TIFF)

Njira za S1. Zothandizira Zipangizo ndi Njira.

onetsani: 10.1371 / journal.pone.0120191.s005

(DOC)

Kuvomereza

Tikuthokoza Dr. Sergio Papalia kuti amuthandize mwaluso.

Zopereka za Wolemba

Zimalengedwa ndipo zinapanga zoyesayesa: RV EP MDS. Anayesa zotsatira: EP MDS DA ECL AF LP AV. Kusanthula deta: RV AP AG SPA. Zopereka zowonjezera / zipangizo / zofufuza: AF EP MDS. Papepalalo analemba: RV SPA EP MDS.

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