Kutsogolo. Behav. Neurosci., 23 March 2016 | http://dx.doi.org/10.3389/fnbeh.2016.00054
Masroor R. Shariff1, Arnauld Belmer1, Mateyu J. Fogarty2, Erica WH Mu2, 
- 1Pulogalamu ya Research Translational ndi Institute for Health ndi Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia
- 2Sukulu ya Sayansi Yachilengedwe, University of Queensland, Brisbane, QLD, Australia
Zakudya zamakono zakhala zokoma kwambiri, zomwe zimachititsa kuti shuga zisamakhalepo kale, makamaka pakati pa achinyamata. Ngakhale kuti kudya kwa shuga kwa nthawi yaitali kumadziwika kuti kumayambitsa matenda opatsirana kwambiri kuphatikizapo kunenepa kwambiri ndi mtundu wa shuga wachiwiri, sichidziwika pang'ono ponena za zotsatira zachindunji zomwe zimakhalapo kwa nthawi yaitali, zowonongeka monga shuga mu ubongo. BChifukwa shuga ikhoza kuyambitsa dopamine mu nucleus accumbens (NAc) mofananamo ndi mankhwala osokoneza bongo, ife tafufuzira kusintha kwa morphology ya neurons mu chigawochi kumapeto kwa masabata (4) ndi maulendo a nthawi yayitali (masabata a 12) monga sucrose yogwiritsiridwa ntchito pogwiritsa ntchito botolo lapakati lawiri la botolo. Tinagwiritsa ntchito madontho a Golgi-Cox kuti tizitsatira timadzi timeneti timene timapanga tizilombo toyambitsa matenda. Timasonyeza kuti kumwa mowa wambiri monga mankhwala otsekemera amachepetsa kuchepa kwa dendritic kutalika kwa nkhono za MSN zofanana ndi makoswe oyenerera zakale. Tinaonanso kuti kukonzanso kwa neuroni kumeneku kunayambitsa kuchepa kwa dendritic complexity. Mosiyana ndi zimenezi, tawona kuwonjezeka kwa msana ku maofesi a distal of NAc shell MSNs kuyambira poti sucrose makoswe odya. Kuphatikizidwa, zotsatirazi zikuwonetsa zotsatira za neuronal za kudya kwa binge monga kwenguva yayitali ya sucrose pa nkhono ya NAc morphology MSN.
Introduction
Pa zaka zapitazi za 40, pakhala kuwonjezereka kolembedwa mukumwa kwa shuga-zotsekemera ndi zakudya zomwe zili ndi shuga wowonjezera (Nielsen et al., 2002; Popkin, 2010; Ng et al., 2012), ndi malipoti owona kuti mpaka 75% ya zakudya zonse ndi zakumwa zili ndi shuga wambiri wowonjezera (Ford ndi Dietz, 2013; Mphuno ndi Chikopa, 2014). Panthawi imeneyi, pakhala kuchulukanso kwakukulu kwa kuchuluka kwa kunenepa kwambiri ndi mtundu wa shuga wachiwiri, makamaka pakati pa achinyamata (Arslanian, 2002; Reinehr, 2013; Dabelea et al., 2014; Fryar et al., 2014). Kafukufuku waposachedwapa awonetsa kuti ana olemera kwambiri komanso olemera kwambiri amadya shuga wochulukirapo, komabe zopereka za shuga yapamwamba zomwe zili ndi zakudya zowonjezera chiwerengero cha ana olemera kwambiri ndi olemera kwambiri zimakhalabe zokangana (Hu, 2013; Mphuno ndi Chikopa, 2014; Bucher Della Torre et al., 2015).
Ngakhale umboni wochulukirapo umasonyeza kuti kudya zakudya za shuga zapamwamba zingapangitse kuti ana ndi achinyamata akule bwino (Malik et al., 2010; Te Morenga et al., 2013; Mphuno ndi Chikopa, 2014), sitinaganizirepo zotsatira za zotsatira zopanda mphamvu zamagetsi zomwe zimabwera chifukwa cha kudya kwambiri shuga. Chochititsa chidwi n'chakuti kachitidwe kachitidwe kaŵirikaŵiri kaŵirikaŵiri kamatuluka pakati pa anthu omwe amadya ndi kusunga shuga wokhala ndi zakudya. Chochititsa chidwi kwambiri ndi chitukuko cha matenda okhudzana ndi kudya, kuphatikizapo kugwirizana komweko kwa zizindikiro za maganizo kuphatikizapo kusowa kwachisonkhezero ndi kupsinjika maganizo (kubwerezedwa mu Sheehan ndi Herman, 2015). Kuonjezera apo, chifukwa chakuti anthu odyera nthawi zambiri amawonetsa kuti sangathe kulamulira komanso amalephera kudziletsa okha, ndiye kuti zikhalidwezi zimakhala chifukwa cha kusintha kwa ubongo m'madera a ubongo omwe amawunika kufunika kwa chakudya chokoma kwambiri (Saper et al., 2002; Lutter ndi Nestler, 2009; Kenny, 2011). Izi zimagwirizananso ndi umboni mwa anthu omwe amasonyeza kuti shuga ndi kukoma zingachititse zilakolako zofanana ndi zomwe zimayambitsidwa ndi mankhwala osokoneza bongo monga mowa ndi chikonga (Volkow et al., 2012).
Ngakhale kuti shuga ndizomwe zimayambitsa matenda, zimakhala zosawerengeka, zomwe zikuwonetseratu zomwe zimapereka chithandizo cha shuga kwambiri kuti zisinthe muzowonjezera mphotho komanso chitukuko cha makhalidwe ozunguza bongo komanso zochitika zowonongeka. (Avena et al., 2008; Benton, 2010; Ventura et al., 2014), akuvomereza kuti pakufunika kufufuzidwe kwina. Kafukufuku wam'mbuyo mwa makoswe awonetsa kuti mwayi wothandizana ndi sucrose umasintha ntchito ya maurotransmitter angapo mkati mwa dongosolo la masolimbic kuphatikizapo dopamine, opioids ndi acetylcholine (Yotchulidwa mu Avena et al., 2008). Kuwongolera mowa ngati sucrose kwasonyezedwa kuti zithandize dopamine kumasulidwa mu nucleus accumbens (NAc), mofananamo ndi mankhwala osokoneza bongo (Avena et al., 2008). Kuwonjezera apo, tawonetsa kuti nthawi yayitali kumwa sucrose pogwiritsira ntchito 24 mwayi wapakati wopangira botolo (Simms et al., 2008) amachititsa kuti nicotinic acetylcholine receptor (nAChR) iwonetsedwe mu NAC (Shariff et al., Mu press). N'zochititsa chidwi kuti tawonanso kuti mankhwala a NAChR amadziwika kuti amatha kupanga dopamine ndi acetylcholine ntchito mu NAC, ndipo zimakhala ndi zotsatira zosiyana pa sucrose mowa panthawi yochepa komanso yayitali (Shariff et al., Mu press).
Ngakhale kuti maphunzirowa asonyeza kufanana kwa kusintha kwa khalidwe ndi matenda a m'mimba chifukwa cha kupititsa patsogolo kwa shuga ndi mankhwala osokoneza bongo, sizidziwika ngati zotsatirazi zimapangitsa kusintha kwa neuronal morphology ku NAc. TIye amasiyana ndi zinthu zoponderezedwa kuphatikizapo cocaine, amphetamine ndi chikotini zomwe zimapangitsa kusintha kwakukulu kwa ma morphology of medium spiny neurons (MSNs) ku NAc, kuphatikizapo kuchuluka kwa msinkhu wambiri ndi kusintha kwa zovuta zedi (Robinson ndi Kolb, 1999, 2004; Li et al., 2003; Crombag et al., 2005). Chifukwa chakuti tawonetsa kale kuti kutayika kwa nthawi yayitali (12 sabata) mowa ndi sucrose pogwiritsa ntchito mapulogalamu apakati a botolo awiri amapanga kusiyana kwa mankhwala a pharmacotherapeutic poyerekeza ndi kudya kwa nthawi yayitali (masabata a 4; Steensland et al., 2007; Shariff et al., Mu press), tinayesa zotsatira za kuchepa kwafupipafupi komanso kwa nthawi yayitali pa MSN morphology mu NAC. Tinalola makoswe achinyamata kuti adye sucrose mofanana ndi 4 (yaifupi) kapena masabata a 12 (nthawi yaitali) ndikuwunika kafukufuku wamaphunziro a NAC MSN kwa makoswe ochepa komanso osadya nthawi yayitali ndikuyerekeza izi ndi maulamulidwe okalamba omwe anapatsidwa mwayi wopezeka madzi okha. Zotsatira zathu zimasonyeza kuti MSN kuchokera ku chipolopolo cha NAc amasinthidwa pakutsatira kanthawi kochepa koma kosakhalitsa, chifukwa cha kuchepa kwa dendritic kutalika, koma kuchuluka kwa dendritic msinkhu wa msana. Komanso, tinapeza kuti ma morphologie a MSN a m'kati mwa NAC analibe othandizira kutsatira kanthawi kochepa komanso kanthawi kochepa. Zotsatirazi zikuwonetsa zotsatira zachinsinsi za kapangidwe ka sucrose kwa nthawi yaitali. Komanso, deta iyi ikuwonetsa kufunikira kwa maphunziro opitilira pofuna kufotokozera kusintha kwa maselo ndi m'maganizo omwe akugwirizana ndi kusintha kwa morphological kwa NAc shell MSNs yomwe imapangidwanso ndi kudya kwapakati, monga kudya kwa sucrose.
Zida ndi njira
Chikhalidwe
Njira zonse zoyesera zinachitidwa malinga ndi Code Australian for Care and Use of Animals for Scientific Purposes, 8th Edition (National Health and Medical Research Council, 2013). Malamulowa adavomerezedwa ndi Komiti ya Queensland University of Technology Animal Ethics Committee ndi Komiti ya University of Queensland Animal Ethics.
Nyama ndi Nyumba
Amuna asanu ndi asanu (amsinkhu) amphongo Amphongo (Kulamulira: 176.4 ± 4.8 g; Sucrose: 178.3 ± 5.0 g) (ARC, WA, Australia), adagwiritsidwa ntchito pulojekiti imodzi® osayenera. Mphunozo zinagwirizanitsidwa ndi momwe nyumba zimakhalira, kuyendetsa, ndi kutembenuka kwapadera masiku 5 isanayambe kuyesedwa. Mphungu zonse zinkaikidwa mu kuwala kozungulira kwa 12-hr / kuwala kwa mdima (kuyatsa pa chipinda cha 9 am) pamodzi ndi makoswe okhwima ndi madzi omwe alipo ad libitum.
Zosakaniza-Kupeza Zipangizo ziwiri Zotsitsila Kumwa Paradigm
Kufika kwa 5% mwachindunji kumatsanulira chisankho cha botolo awiri kumwa mafuta (Simms et al., 2008) anasinthidwa kuchokapo Wanzeru (1973). Zonsezi zimaperekedwa m'mabotolo a pulasitiki omwe anamaliza maphunziro a 300 ml okhala ndi zipangizo zoledzera zamagetsi zopangidwa ndi zipangizo zopanda utoto. Miyeso ya botolo lirilonse linalembedwa musanalankhulidwe ka botolo. Mabotolo awiri ankawonekera panthaŵi yomweyo: botolo limodzi lokhala ndi madzi; botolo lachiwiri lokhala ndi 5% (w / v) sucrose. Kusungidwa kwa botolo la 5% (w / v) la sucrose linasinthidwa ndi aliyense kuwonetsetsa kuti azitha kukonda mbali. Mabotolo ankayesedwa 24 h pambuyo pa madzi, ndipo miyeso inatengedwa ku 0.1 yapafupi. Mlingo uliwonse wa makoswewo unayesedwa kuti awerengere magalamu a sucrose kudya kwa kilogalamu ya kulemera kwa thupi. Patsiku la 1 la nthawi yoledzera, makoswe (n = 6-9) anapatsidwa mwayi wa botolo limodzi la 5% (w / v) sucrose ndi botolo limodzi la madzi. Pambuyo pa 24 h, botolo la sucrose linalowetsedwa ndi botolo lachiwiri la madzi limene linkapezeka ku 24 yotsatira. Chitsanzo ichi chinabwerezedwa Lachitatu ndi Lachisanu. Mphuno inali ndi mwayi wochuluka wa madzi masiku ena onse. Kusakaniza mofanana ndi sucrose kunayambitsa kuchuluka kwa sucrose kudya (ml) pa nthawi (Zoonjezerapo Chithunzi 1) ndipo ankatsagana ndi miyezo yoyenera ya kumwa moyenera chifukwa cha kulemera kwa thupi [20 ± 5 g / kg ya 5% (w / v)] pakapita masabata [~ 4 masabata (masewera a zakumwa za 13)] komanso nthawi yaitali [ Masabata 12 (37). Gulu losiyana la makoswe (n = 6-9) anapatsidwa mwayi wopezeka madzi m'mabotolo onse (ie, palibe sucrose) pansi pa zofanana zomwe zafotokozedwa pamwambapa. Kulemera kwa thupi kunenepa ndi sucrose makoswe otsala pakutha kwa nthawi yayitali anali 405.7 ± 40.8 g ndi 426.4 ± 31.2 g moyenera. Pakutha kwa nthawi yayitali, kulemera kwa thupi kumagulu ndi ma sucrose anali 578.8 ± 53.4 g ndi 600.2 ± 45.2 g.
Golgi-Cox Kusunga
Pambuyo pake, makoswe omaliza adatengedwa kuchoka ku malo osungirako nyama kuti akwaniritse zitsanzo za ubongo ku malo ake ophunzirira a Sukulu ya Biomedical Sciences, University of Queensland (St Lucia, Australia). Miyeso yonse yovomerezeka idatengedwera kuti achepetse kupanikizika paulendo, motere, makoswe amaloledwa kubwezera usiku womwewo. Tsiku lotsatira, makoswe ankaperekedwa ndi sodium pentobarbital overdose (60-80 mg / kg, ip Vetcare, Brisbane, Australia) ndipo osagwiritsidwa ntchito mosagwiritsidwa ntchito ndi ~ 300 ml chodzidzimutsa chamadzimadzimadzi omwe anali, (mM): 130 NaCl, 3 KCl, 26 NaHCO3, 1.25 NaH2PO4, 5 MgCl2, 1 CaCl2, ndi 10 D-shuga. Ng'ombe iliyonse idakonzedwanso ndipo ubongo unachotsedwa ndikugwiritsidwa ntchito mumdima wa Golgi-Cox womwe unali ndi 5% potassium dichromate, 5% potassium chromate, ndi 5% mankhwala othandizidwa ndi Sigma-Aldrich omwe anapangidwa masiku atsopano a 3 asanapereke nsembe monga tafotokozera poyamba (Rutledge et al., 1969). Njira zotchedwa Golgi-Cox zotsekedwa ndi njira zotsekemera zinasinthidwa kuchokera Ranjan ndi Mallick (2010). Nthenda zamphongo za sucrose zochepa zomwe zimadya nyama zinkapangidwira masiku a 6 pa 37 ° C, pamene ubongo wa nyama zam'mazira zowononga nthawi yayitali unayambika masiku a 10, ndi kusintha kokha ku njira yatsopano ya Golgi-Cox pambuyo pa tsiku la 4 la kutsekedwa.
Potsata makulitsidwe, 300 μm zigawo zina zidadulidwa pogwiritsa ntchito microissome Zeiss Hyrax V50 (Carl Zeiss, Germany). Zigawo zinayikidwa sequentially mu 24-bwino mbale zodzazidwa ndi 30% (w / v) sucrose mu salimo 0.1 M phosphate ogulitsidwa monga momwe tafotokozera (Ranjan ndi Mallick, 2010). Mwachidule, magawo anali otayika mu 50% ethanol kwa 5 min, kenaka anaikidwa mu 0.1 M NH4OH yankho la 30 min, lopukuta kawiri ndi madzi osungunuka kwa 5 min ndikuyika ku Fujihunt film fixer (Fujifilm, Singapore) kwa 30 min mu mdima. Magawowo amatsukidwa kawiri m'madzi osungunuka kwa 2 min iliyonse ndipo amatha kutaya madzi m'thupi la 70, 90, 95, ndi 100% ethanol kawiri kwa 5 min iliyonse. Zigawozo zinachotsedwa mu njira ya CXA (1: 1: 1 chloroform: xylene: mowa) kwa 10 min ndipo inakonzedwa ku DPX (Sigma-Aldrich) pa zithunzi za Superfrost Plus (Menzel-Glaser, Lomb Scientific, Australia) ndi kutsekedwa (Menzel-Glaser, Germany). Zithunzizo zinasiyidwa mumdima kuti ziume ka firiji usiku wonse.
Kusankha kwa Neuronal ndi Tracing mkati mwa Nucleus Accumbens
Zigawo za Coronal pakati pa bregma + 2.8 ndi + 1.7 zinayang'aniridwa ndi MSN m'munsi ndi chipolopolo cha NAc, pogwiritsa ntchito chithunzithunzi cham'mbuyochi ndi kumangoyamba kutsogolo monga zizindikiro pogwiritsa ntchito atlas ubongo (atlas)Paxinos ndi Watson, 2007) (Chithunzi 1). Mpikisanowu umagwira ntchito mu Neurolucida 7 (MBF Bioscience, VT, USA) amagwiritsidwa ntchito poyerekeza chigamba cha NAc ndi chipewa cha NAC mu chidutswa chilichonse (Chithunzi 2). Pakati pa 2 ndi 9 neurons pa dera lililonse pamtundu wa nyama zimatengedwa chifukwa cha dendritic measurements pogwiritsa ntchito cholinga cha 63x kapena zovuta za msana (zomwe zimatchedwa spines pa 100 μm) pogwiritsa ntchito 100x cholinga cha Zeiss Axioskop II (Carl Zeiss, ku Germany) xyz siteji yothamangitsidwa ndi Neurolucida® Mapulogalamu a 7 (MBF Biosciences, VT, USA). Kufufuza konse kunkachitidwa khungu kokhudza mankhwala. Makhalidwe a Golgi-Cox omwe anapangidwa ndi neuroni anafufuzidwa mwanjira yofanana ndi malipoti apitalo (Klenowski et al., 2015).
Chithunzi 1. Mapu akuwonetsera malo omwe amatha kukhala ndi timadzi timene timene timakhala timene timapangidwira kuchokera ku nucleus accumbens pachimake ndi chipolopolo cha 4 ndi 12 sabata imawombera makoswe ndi machitidwe ofanana zakale. Mapepala awiri apamwamba amasonyeza malo amodzi omwe amachokera ku nucleus accumbens pachimake ndi chipolopolo cha 4 sabata (triangles) ndi sucrose (mabwalo) nyama. Zitsulo ziwiri za pansizi zimasonyeza malo a zinyama zam'nyumba zonyamulidwa kuchokera ku 12 sabata (triangles) ndi sucrose (mabwalo) nyama.
Chiwerengero cha Kusanthula
Kutanthauzira ndi kulakwitsa kwakukulu kwa tanthawuzo (SEM) kunawerengedwera pa deta iliyonse yosankhidwa ndi nyama monga n, pogwiritsa ntchito deta yamtundu wa morphometry kuchokera pachimake kapena chipolopolo cha NAC MSNs (n = 7 ya shell ya NAc ndi n = 6 kwa NAC core-week-week, n = 9 yamagulu a masabata 12). Zomwe zawonetsedwa, Wophunzira Woperewera wopanda tailed awiri t-Atsuka njira ziwiri kapena mavoti a Bonferroni pambuyo poyesera zinachitidwa kuti ziwonongeke zonse zomwe zikuphatikizapo kuyerekezera magulu a gulu, pogwiritsa ntchito GraphPad Prism version 6.02 (GraphPad Software, San Diego, CA). Chiwerengero cha chiwerengero chinavomerezedwa pa P <0.05. Deta yonse mu gawo la zotsatira imaperekedwa ngati njira ± SEM. Kusintha kwa peresenti kumawerengedwa molingana ndi mtengo wowongolera.
Results
Neuroni Zam'katikati Zochokera ku Nucleus Accumbens Shell Zakhala Zochepetsera Kutalika kwa Dendritic, Kutsika kwa Dendritic Complexity koma Kuwonjezeka Kwambiri Kunenepa Kwambiri pa Maofesi a Nthambi Zowonongeka Kumatsatira Kugwiritsa Ntchito Pafupipafupi Kwambiri Koma Osakhalitsa
Pambuyo pa masabata angapo (masabata a 4) atayamwa mankhwala, panalibe kusiyana kwakukulu mu kapangidwe ka NAC MSN morphometric parameters (Table 1). Panalibenso kusiyana kwakukulu pakati pa kanthawi kochepa kowonongeka kwa madzi ndi madzi ndi NAC shells MSNs mu zofukufuku zokhudzana ndi centrifugal nthambi nthambi. Zomwe, zigawo za dendritic pa dongosolo la nthambi (P = 0.4111), kutanthauza kutalika kwa dendritic pa dongosolo la nthambi (P = 0.5581) ndipo amatanthawuza msinkhu wa msana pa dongosolo la nthambi (P = 0.2977, ANOVAs ziwiri) sizinali zosiyana kwambiri pakati pa magulu. Mapu a malo akuwonetsera malo ofanana ndi ma neuroni omwe amasonyezedwa mu Chithunzi 1.
Gulu 1. Zomwe zimachititsa kuti mitsempha yambiri ikhale yamtundu wa nucleus accumbens chipolopolo cha kanthawi kochepa kamene imadya makoswe ndi mayendedwe a madzi okalamba.
Pambuyo pa nthawi yayitali (masabata a 12) a sucrose osakanizidwa, chiwerengero chonse cha dothi cha NAC chimafooka ndi 21% poyerekeza ndi kuwononga madzi (Madzi: 1827 ± 148 μm, n = 9; Sucrose 1449 ± 78 μm, n = 9, *P = 0.0384, Yophunzira yopanda ma tail awiri t-kutsiriza, Chithunzi 2, Table 2). Kuyerekeza kwa chiwerengero cha mapuloteni a dendritic (nodes) ndi mapeto a dendritic pakati pa madzi ndi magulu a sucrose awonetsa zovuta zochepa (ngakhale zosafunika) mu nkhono za MSNs (nodes: Water 12.9 ± 1.4 n = 9, Sucrose 10.1 ± 0.8 n = 9, P = 0.0879; Mapeto: Madzi 17.9 ± 1.4 n = 9, Sucrose 14.8 ± 0.7 n = 9, P = 0.0657, Yophunzira yopanda ma tail awiri t-kuposa, Table 2). Panalibe kusintha mu buku la soma (P = 0.9400), kutanthauza kutalika kwa mtengo wa dendritic (P = 0.1646) kapena kuchuluka kwa msinkhu wa msana (P = 0.3662) mu nkhono ya NAc MSNs kuchokera ku makoswe omwe amadya nthawi yayitali poyerekeza ndi kulamulira madzi. Mapangidwe awa a morphometric akufotokozedwa mwatsatanetsatane 2.
Chithunzi 2. Kuchepetsa kutalika kwa dborritic arbor kutalika ndi kuwonjezeka kwa dintritic spine density of spin neurons (MSNs) yochokera ku nucleus accumbens (NAc) chipolopolo cha makoswe amtundu wambiri wa sucrose poyerekeza ndi makoswe olamulira. (A, B) onetsani maonekedwe a (pamwamba) ndi nthawi yayitali (12 sabata) sucrose (m'munsi) yochitidwa bwino z-kujambula zolemba za Golgi zosasinthidwa za MSN kuchokera ku chipolopolo cha NAc (kukuza 63x). Kusintha kwa (A, B) Kuwonetsa kulamulira komanso nthawi yayitali ya sucrose ikuwonetseratu zojambula za Golgi-zopangidwa ndi MSN zowonongeka ndi zowonongeka kuchokera ku NAC shell (100x kukula). (C) amasonyeza madera omwe amatchedwa MSNs omwe adasankhidwa kuchokera mu phunziro lino. (D) Zimasonyeza kuti pulogalamu yamtundu wa MSN yotchedwa Dendritic arbor (yotanthawuzira ± SEM) imakhala yochepa kuchokera ku chipolopolo cha NAC m'miyala yambiri ya sucrose poyerekeza ndi kulamulira (ozungulira), ophunzira osayenerera t-ndipo, *P <0.05, n = 9; kulamulira ndi n = 9; Pulogalamu ya 12 imawombera. (E) Zimasonyeza kuti malo osokoneza bongo amatanthauza kuti MSN dendritic mtengo (kutanthauza ± SEM) kuchokera ku chipolopolo cha NAC m'miyala yambiri ya sucrose poyerekeza ndi maulamuliro (ozungulira), ophunzira osayenerera t-kuposa, P > 0.05, n = 9; kulamulira ndi n = 9; Pulogalamu ya 12 imawombera. Kusanthula kachitidwe ka nthambi (kutanthauza ± SEM) ya nambala ya dendritic nambala iliyonse pa nthambi (F), kutanthauza kutalika kwa dendritic pa dongosolo la nthambi (G) komanso dendritic msinkhu wa msana pamaofesi a nthambi (H). Kugwiritsa ntchito mankhwala osokoneza bongo kwa nthawi yayitali kunachepetsa kutalika kwa dendritic ku maofesi a distal branch (5 +) ndi kuchulukitsitsa kwa msana wambiri pamasitima a distal (4 +) poyerekeza ndi maulamuliro (G, H), njira ziwiri za ANOVA ndi mayeso a post-Bonferroni, *P <0.05, **P <0.01, n = 9; kulamulira ndi n = 9; yaitali sucrose. Zolemba Zofukiza: (A, B) = 20 μm; zofunikira (A, B) = 10 μm; (C) = 1 mm.
Gulu 2. Mitundu yambiri yamapiko a minofu yambiri yamkati yomwe imachokera ku nucleus accumbens chipolopolo cha sucrose kwa nthawi yaitali chimawononga makoswe ndi mayendedwe a madzi okalamba.
Potsata malingaliro a dendritic morphology a long-sucrose omwe amadya NAc shell MSNs, ife tinaganizira dendritic arborizations ndi msinkhu wa msana motsatira makhalidwe awo a nthambi. Kufufuza kwathu kwakukulu kwa mitengo ya dendritic imatanthauzira chiwerengero cha zigawo za dendritic pa dongosolo la nthambi, kutalika kwa magulu a dendritic pa dongosolo la nthambi ndipo kumatanthauza kusinthana kwa msana pa dongosolo la NAc shell MSNs ya madzi olamulira ndi yaitali sucrose makoswe odya. Chidule cha deta ndi deta za dongosolo la nthambi zikufotokozedwa mu Table 3.
Gulu 3. Makhalidwe oyendetsa nthambi kuti azitsitsimutsa kwambiri kuchokera ku nthawi yayitali ya sucrose ndi makoswe akumwa madzi.
Nambala yeniyeni ya nthambi ya dendritic pa tsamba lonse la nthambi ya NAc shell MSNs inachepetsedwa kwambiri mu nthawi yayitali sucrose kudya makoswe poyerekezera ndi kulamulira madzi (**P = 0.0015, ANOVA njira ziwiri). Mayendedwe a Bonferroni pambuyo poyera anawonetsa chikhalidwe cha kuchepa kwa magulu a nthambi ku 4th (Madzi: 5.2 ± 0.9, n = 9; Sucrose 3.3 ± 0.8, n = 9, P = 0.0675, Chithunzi 2F, Table 3), ndi dongosolo la 5th komanso pamwamba pa malamulo a nthambi (Madzi: 3.3 ± 0.7, n = 9; Sucrose 1.2 ± 0.3, n = 9, P = 0.0566, Chithunzi 2F, Table 3). Kutalika kwa gawo la dendritic kutalika pa nthambi ya NAc shell MSNs inachepetsanso kwambiri mu nthawi yayitali sucrose kudya makoswe poyerekeza ndi kuchepetsa madzi (*P = 0.0444, ANOVA njira ziwiri). Mayendedwe a Bonferroni pambuyo adawonetsa kuchepetsa kwa 55% pa nthambi za 5th ndi kupitirira (Madzi: 53.9 ± 7.2 μm, n = 9; Sucrose 24.1 ± 7.5 μm, n = 9, **P = 0.0038, Chithunzi 2G, Table 3).
Kusanthula kayendedwe ka nthambi kunasonyeza kuwonjezeka kwakukulu kwa dendritic msinkhu wa msana wa NAc shell MSNs ya nthawi yaitali sucrose kudya makoswe poyerekeza ndi machitidwe (*P = 0.0124, ANOVA njira ziwiri). Mayendedwe a Bonferroni pambuyo pake anasonyezera kuwonjezeka kwa msana kwa 57% pamtunda wa districts 4th ndi kupitirira (Madzi: 33.4 ± 4.2, n = 9; Sucrose 52.5 ± 6.8, n = 9, P = 0.0271 *, zowerengedwera za Ziwerengero 2A, B, H, Table 3). Zithunzi zoimira mawonedwe onse a MSN ndi kuwerengeka kwa msinkhu wamtunduwu (inset) zikuwonetsedwa muzinthu 2A, B.
Kuphatikizidwa pamodzi, zotsatirazi zikuwonetsa kuti mankhwala osakaniza a sucrose afupikitsa alibe zotsatira zochepa pamakhalidwe a MSN mu chipolopolo cha NAC. Komabe, potsatira kumwa kwa nthawi yayitali, pali kuchepa kwakukulu mu kutalika kwake kwa arboral and complexity, makamaka m'matawuni otchedwa distal dendritic. Kuchulukanso kwa msinkhu wochulukirapo m'thupi kumatulukanso kumawonekedwe a MSNs a NAc a makoswe ambiri omwe amadya makoswe.
Neuroni Zang'onoting'ono Zochokera ku Nucleus Accumbens Core zakhala zochepetsedwera kuwonjezeka kwa nthambi kumapeto kwa nthawi yaitali koma osati nthawi yayitali yogwiritsira ntchito Sucrose
Pambuyo pafupipafupi ya sucrose yogwiritsiridwa ntchito, panalibe kusiyana kwakukulu mu NAC yofunikira MSN morphometric magawo (Table 4). Panalibe kusiyana kwakukulu pakati pa 4-week-sucrose ndikugwiritsa ntchito mphamvu zamadzimadzi zowonongeka kwa madzi mu zofufuza zogwirizana ndi dongosolo la nthambi ya centrifugal. Zomwe, zigawo za dendritic pa dongosolo la nthambi (P = 0.7717), kutanthauza kutalika kwa dendritic pa dongosolo la nthambi (P = 0.2096), ndipo amatanthawuza msinkhu wa msana pa dongosolo la nthambi (P = 0.3521, ANOVAs ziwiri) sizinali zosiyana pakati pa magulu.
Gulu 4. Mitundu yambiri ya chikhalidwe cha mitsempha yambiri yamkati yomwe imachokera pamtengowo imakhala pamtunda wa kanthawi kochepa yomwe imadya makoswe ndi zaka zomwe zikufanana ndi kayendedwe ka madzi.
Kusakaniza kwa sucrose kwa nthawi yayitali kunalibe phindu pa NAC yayikulu MSN morphometric magawo (Table 5). Nambala yeniyeni ya nthambi ya dendritic pa tsamba lonse la nthambi ya MSN ya MSN yayamba kuchepetsedwa kwambiri poyerekeza ndi makoswe poyerekeza ndi kayendedwe ka madzi (*P = 0.0416, njira ziwiri za ANOVA), komabe panalibe kusiyana kwakukulu kwa kutalika kwa dendritic kutalika kwa dongosolo la nthambi (P = 0.0995) ndipo amatanthawuza msinkhu wa msana pa dongosolo la nthambi (P = 0.4888, ANOVAs ziŵiri) pakati pa MSN mu nthenda ya NAc ya makoswe omwe amadya nthawi yaitali poyerekeza ndi kulamulira madzi. Kuphatikizidwa pamodzi, deta yathu imasonyeza kuti NAC imakhala yosamvetsetseka nthawi yayitali poyerekeza ndi MSNs kuchokera ku NAC shell.
Gulu 5. Zomwe zimachititsa kuti mitsempha yambiri ikhale yamtundu wa nucleus yomwe imakhala pamtunda wa sucrose wautali wa zaka zambiri..
Kukambirana
Kuwonjezeka kwa chakudya chokoma kwambiri ku zakudya za kumadzulo sikunangowonjezera kuwonjezeka kwachuma komanso kulemera kwachuma kwa kunenepa kwambiri ndi mtundu wa shuga wachiwiri, ndipo kwachititsa kuti zikhale zoyambitsa matenda monga kudya mowa kwambiri (Swanson et al., 2011; Kessler et al., 2013; Davis, 2015). Ngakhale mankhwala a shuga kuphatikizapo fructose ndi sucrose amakhalabe olingalira, pali kufanana kwakukulu mu makhalidwe ndi neural correlates omwe amasonyeza chifukwa cha kudya ndi kumwa mankhwala osokoneza bongo nthawi yayitali (Avena et al., 2008, 2011). Kuphatikiza apo, shuga imathandizira kuyendetsa mphotho zamaubongo m'njira yofanana ndi mankhwala osokoneza bongo (Volkow et al., 2012), ndipo zotsatira kuchokera ku maphunziro a anthu zimasonyeza kuti shuga ndi zokoma zingachititse zilakolako zomwe zikufanana kwambiri ndi omwe amamwa mankhwala osokoneza bongo monga mowa ndi chikonga (Volkow et al., 2012). Choncho tinagwiritsira ntchito chitsanzo cha binge-sucrose m'makoswe kuti tipeze zotsatira za masabata (4 masabata) komanso maulendo a nthawi yaitali (masabata a 12) omwe amawagwiritsa ntchito pa neuronal morphology ya MSNs mu NAC, zomwe zimasinthidwa ndi shuga ndi mankhwala osokoneza bongo. Timasonyeza kuti ma MSN ochokera ku nkhono ya NAc ya nthawi yayitali ya sucrose yodyera makoswe adachepetsa kwambiri kutalika kwa dendritic ndi kuvomereza, koma kuwonjezeka kwa distal dendritic msinkhu wa msana. Kugwiritsa ntchito mankhwala osakanizika kwa nthawi yaitali sikunakhudze ma morphologie a MSNs kuchokera ku NAC, pomwe kanthawi kochepa mankhwalawa sakanakhala ndi zotsatirapo zambiri pa kafukufuku wamaphunziro a MSN kuchokera ku NAC core kapena shell. Zotsatira izi sizisonyezeratu zotsatira zowonjezereka za kumwa mowa wambiri monga sucrose kudya pa neuronal morphology ya NAc shell MSNs, koma amatsindikanso zotsatira zomwe zingakhale zovulaza za kumwa kwa nthawi yayitali shuga wokhala ndi zakudya.
The NAc, yomwe imakhala mbali ya ventral striatum, imaphatikizapo ma MSNs, omwe amachititsa kuti thupi lawo likhale laling'ono kwambiri ndi mazenera ambiri omwe ali ndi dendritic ndi mkulu wa msana (Kemp ndi Powell, 1971; Graveland ndi DiFiglia, 1985; Rafols et al., 1989; Kawaguchi ndi al., 1990). Nkhono za Glutamatergic ndi dopaminergic ndizo zikuluzikulu zikuluzikulu zomwe zimaphatikizapo NAC, makamaka kulankhulana ndi ma dendritic shafts ndi spines a MSNs (Groves, 1980; Kaiya ndi Namba, 1981; Groves et al., 1994). Makamaka, chigwirizano cha NAc ndi chikhazikitso chakuthupi chimalandira zowonjezera zowonjezera kuchokera kumadera osiyana omwe amagwira ntchito (Brog et al., 1993). Nkhono ya NAc imasamalidwe ndi maulendo okondweretsa kuchokera kumadera osiyana siyana monga hippocampus, thalamus ndi amygdala (Brog et al., 1993; Wright ndi Groenewegen, 1995). Kafukufuku wakale asonyeza kuti zotsatirazi zowonongeka zimagwira ntchito yofunika kwambiri pamakhalidwe ndi zolinga zotsatiridwa monga chakudya ndi mphotho kufunafuna (Maldonado-Irizarry et al., 1995; Kelley ndi Swanson, 1997; Reynolds ndi Berridge, 2003; Richard ndi Berridge, 2011). Chinthu china chomwe chimaperekedwa ku NAC MSNs chimachokera ku dopaminergic afferents yomwe ikuchokera ku ventral tegmental (Lindvall ndi Björklund, 1978; Veening et al., 1980; Kalivas ndi Miller, 1984). N'zochititsa chidwi kuti kafukufuku wakale pogwiritsira ntchito mitundu yofanana ya shuga akuwonetsetsa kuti zotsatira zake zowonjezera zowonjezera zimayambitsa kuchuluka kwa dopamine ya extracellular mu NAc chimodzimodzi (ngakhale pang'ono) kugwiritsa ntchito mankhwala osokoneza bongo (Rada et al., 2005; Avena et al., 2006), ndipo amatha kupanga dopamine receptor expression (Colantuoni et al., 2001, 2002) m'kati mwa NAC ndi chipolopolo. Chochititsa chidwi, kuti kudya mowa kwambiri monga sucrose kumapangitsa kuti chiwerengero cha anthu azidya mofulumira pakapita nthawi mofananamo ndi kudzipangira okha mankhwala osokoneza bongo monga cocaine ndi heroin (Ahmed ndi Koob, 1998; Ahmed ndi al., 2000, 2003) zomwe zikukhudzana ndi chitukuko cha "chikhalidwe choledzera".
Kufufuza kwathu kwa nthambi yotchedwa morphometry kumasonyeza kuti kuchepa kwa dendritic kutalika kwa NAc shell MSNs chifukwa cha kudya kwa nthawi yaitali sucrose, zotsatira zake makamaka chifukwa cha kuchepa kwa maofesi a distal branch. Tinawona kuchepetsedwa kwa matalala osiyana siyana (4th ndi 5th dongosolo ndi pamwamba pa malamulo a nthambi) ndipo kuchepa kwakukulu kumatanthauza kutalika kwa 5th dongosolo ndi pamwamba pa dendrites, kuphatikizapo kuchuluka kwa msana m'magawo awa. Chinthu chofala chomwe chingathe kuwonetsa mtundu uwu wa kukonzanso kwa dendritic kumaphatikizapo kusintha kosinthika kwa synaptic ndi / kapena ntchito (Russo et al., 2010). Kafukufuku wammbuyo asonyeza kuti maseŵera a glutamatergic pa MSN amapangidwa makamaka pamphepete, makamaka pa distal dendrites (Groenewegen et al., 1999). Kuonjezerapo, kugwirizanitsa dopamine ndi glutamatergic kuchokera ku prefrontal cortex (Sesack ndi Pickel, 1992), hippocampus (Totterdell ndi Smith, 1989; Sesack ndi Pickel, 1990), ndi amygdala (Johnson et al., 1994) zakhala zikuwonedwa pa madontho a dendritic a MSNs. Zomwe zikuchitika pamodzi ndi kuchuluka kwa msinkhu wa msana pambuyo poti mankhwala a sucrose akuwonetsedwa mu phunziro lathu, kuthandizira kupanga mapangidwe owonjezereka opititsa patsogolo. Choncho, kuthekera kumene kumachitika komwe zotsatira zosalekeza zomwe zimayambitsidwa ndi kupuma kwapadera monga sucrose kudya zimathandiza kuti ntchito yowonjezereka ya synaptic iwonjezeke ku distal dendrites a MSNs mu nkhono ya NAc. Chifukwa chake, kuchepetsa ndi / kapena kubwezeretsa anthu oterewa kumatha kupyolera mu njira yokhala ndi synaptic homeostatic (Reissner ndi Kalivas, 2010), komabe izi zimatsimikiziridwa.
N'zochititsa chidwi kuti Crombag ndi anzake akuwonetsetsa kuti palibe chiwerengero cha msinkhu wochulukirapo m'kati mwa NAC pambuyo pa sabata la 4 lomwe limagwiritsidwa ntchito pogwiritsa ntchito mpweya wozizira pang'onopang'ono ngakhale kuti mwapeza zambiri mwamphamvu komanso mwapamwamba kwambiri poyerekeza ndi sucrose poyerekeza ndi amphetamine (Crombag et al., 2005). Kuwona kwawo kusakhala kusinthika kwa msinkhu wa msana pamasabata a 4 kumawonetsa zomwe tasanthula. Mosiyana ndi zimenezi, phunziro lathu likuwonetsa kuti kutsata kwa nthawi yaitali (12 sabata) kuwonetsetsa kwa mankhwala osakanizika a sucrose, pali kuwonjezeka kwakukulu kwa kutalika kwa msana m'magulu a MSN a makoswe a sucrose. Kuwonjezera apo, labotale yathu yasonyeza kale kuti nthawi yayitali (12 sabata) kuyamwa mowa umathandizira kusiyana kwa mankhwala kwa pharmacotherapeutics zomwe zawonetsedwa kuti zithetse dopamine ndi acetylcholine mayankho pa mlingo wa NAc (Shariff et al., Mu press). Pogwirizanitsidwa, izi zikusonyeza kuti nthawi yayitali (masabata a 12 ndi kupitirira) amachotsa kufotokozera, zomwe zikuwonetseratu zochitika zenizeni za dziko lapansi, zimayambitsa kusintha kwa morpholoji pamtundu wa NAc.
Ponena za mankhwala osokoneza bongo, kubwerezedwa kwa mankhwala osiyanasiyana kumabweretsa kusintha kosatha mu kapangidwe kake ka dendrites ndi dendritic spines. Mwachitsanzo, amphetamines ndi cocaine zonse zimachulukitsa msinkhu wa msana mu NAC mu zipolopolo zonse ndi pakati (Robinson ndi Kolb, 2004). Kuwonetseratu kwapachikale kwawonetsanso kuti kumawonjezera msinkhu wa msana mu chipolopolo cha NAc. Mosiyana ndi zimenezi, kufotokoza kwa morphine kumachepetsa kuchepa kwa msana komanso maofesi a dendritic (Robinson ndi Kolb, 2004). Ponena za kudya kwa sucrose kwa nthawi yayitali, tinawona kuchuluka kwa msinkhu wa msana wofanana ndi amphetamine, cocaine ndi chikotini komanso mosiyana ndi zotsatira za morphine. Komabe, mosiyana ndi amphetamine ndi cocaine, koma mofanana ndi chikonga, kuwonjezeka kwa msinkhu wa msana pa nthawi yayitali ku sucrose kumangokhala ku chipolopolo cha NAC. N'zosangalatsanso kuti kusintha kwa nthambi ya dendritic (Robinson ndi Kolb, 1999) ndi msinkhu wa msinkhu (Li et al., 2003) zopangidwa ndi amphetamine kapena cocaine zimangokhala kwa azimayi otchuka a MSN ku NAC, omwe amasonyeza zomwe tafufuza mu phunziro lathu. Komanso, ndikuthandizira kusintha komwe tafotokozedwa pamwambapa, kuyambitsanso mankhwalawa kumapangitsa kuti mphamvu ya synaptic yowonjezereka ikhale pa accumbal dopamine neurons (Stuber et al., 2008b) komanso zina zigawo zikuluzikulu za mesolimbic mphotho njira (Stuber et al., 2008a; Chen et al., 2010). Pogwiritsidwa ntchito, izi zimapangitsa sucrose kukhala njira yabwino kwambiri yogwiritsira ntchito mankhwala osokoneza bongo pambuyo pa nthawi yayitali, yomwe ikugwirizana ndi zotsatira zowonongeka.
Ngakhale kuti kufufuza kwina kuli kofunika kuwululira njira zamagetsi ndi synaptic zomwe zimapangitsa kusintha kwa morphological kuwonedwa mu phunziro lino, zotsatira zathu zimasonyeza zotsatira za neuronal zomwe zimapangidwa ndi nthawi yayitali ya sucrose. Makamaka, kulingalira kosaganiziridwa mu phunziro lathu ndiko ngati zotsatira za morphological zotsatira za sucrose zingathenso kuchitidwa ndi osalora okoma monga saccharin. Pankhaniyi ndifunikira kuzindikira kuti Lenoir ndi anzake akuwonetsa kuti kukoma kokoma kumaposa cocaine mphotho, zikhale zopangidwa ndi saccharin kapena sucrose (Lenoir et al., 2007). Kuwonjezera pamenepo, kafukufuku waposachedwapa wofalitsidwa ndi labu lathu (Shariff et al., Mu press) amasonyeza kuti varenicline, nicotinic acetylcholine receptor partial agonist inachepetsera zonse sucrose ndi saccharin kudya mu makoswe potsatira ndondomeko yowonjezera yowonjezera yomwe imagwiritsidwa ntchito mu phunziro lino. Zochititsa chidwi, kafukufuku wakale awonetsa zofanana ndi zotsatira zoopsa za osalora zokoma monga saccharin ndi sucrose pa mlingo wa NAc (Scheggi et al., 2013; Tukey et al., 2013; Carelli ndi West, 2014). Komabe, kufufuza kwina kufunikira kudziwa ngati osalora zotsekemera angathe kuwonetsa zotsatira za nthawi yaitali zofanana ndi kusintha kwa morpholoji ya kapangidwe ka NAC ma MSN omwe amachitidwa ndi mankhwala osakanizidwa a sucrose omwe akupezeka pano.
Kupanda mphamvu pa NAC MSN morphologia pamapeto pake, posonyeza kufunika kochita kafukufuku wa nthawi yayitali kuti aone zotsatira za kugwiritsa ntchito mankhwala osokoneza bongo nthawi yaitali kapena mphotho monga sucrose. Ponena za kudalira, osati kokha mobwerezabwereza kuledzera ndi kubisa zofunika zigawo zikuluzikulu za kusokoneza bongo, umboni wochulukirapo wasonyeza kuti kusintha kwa kudalira ndi njira yopitilira yomwe nthawi zambiri zimachitika kwa nthawi yaitali. Ngakhale kuti shuga imakhalabe yosatsimikizika, kukhala ndi chizoloŵezi cha mankhwala ena osakhala mankhwala monga kugonana, njuga ndi chakudya chikufufuzidwa mochulukirapo. Zotsatira za phunziroli zimaphatikizapo chidziwitso kuti shuga monga sucrose angathe kukhala ndi mankhwala osokoneza bongo pambuyo pa nthawi yayitali, kumwa mowa. Zotsatira zathu zimakhudzanso chiwerengero chowonjezeka cha ana ndi achinyamata omwe amadya zakudya zopanda thanzi (shuga wapamwamba ndi kudya mowa) kuti akhale wamkulu. Malingana ndi chiopsezo chowonjezereka chokhala ndi zotsatira zamagetsi ndi kotheka kuti zotsatira za ubongo ndi zamaganizo zomwe zimakhudza maganizo ndi zowonjezera zingathenso chifukwa cha makhalidwe amenewa.
Zopereka za Wolemba
Anagwira nawo kupanga kafukufuku: PK, SB. Zotsatira zochitidwa: PK, MS, AB, MF, EM. Kusanthula deta: PK, MF, MS. Anatanthauzira deta ndikuthandizira kulembera malembawo: PK, MS, MF, EM, MB, SB. Olemba onse amawerenga ndi kuvomereza malemba omaliza kuti apereke.
Kutsutsana kwa Chidwi
Olembawo akunena kuti kufufuza kunkachitika popanda mgwirizano uliwonse wa zamalonda kapena zachuma zomwe zingatengedwe kuti zingatheke kukangana.
Owongolera SC, SA ndi omwe akukonzekera Editor adalengeza kuyanjana kwawo, ndipo kusamalira Mkonzi kumanena kuti ndondomekoyi idakwaniritsidwanso ndi ndondomeko yoyenera.
Kuvomereza
Ntchitoyi inathandizidwa ndi ndalama kuchokera ku Australian Research Council (FT1110884) kupita ku SB ndi National Health and Medical Research Council (1061979) kwa SB ndi MB.
Zowonjezera Zowonjezera
Zowonjezera Zowonjezera pa nkhaniyi zitha kupezeka pa intaneti pa: http://journal.frontiersin.org/article/10.3389/fnbeh.2016.00054
Zowonjezera Chithunzi 1. Sucrose kudya ndi kukonda kuchokera ku 4 ndi 12 sabata imatulutsa makoswe odya. (A, B) Onetsetsani kuti mchere umakhala wochuluka kwambiri (ml) pa 4 ndi masabata a 12. (C, D) onetsetsani kuti amakonda kwambiri sucrose pa madzi nthawi ya sucrose.
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Mfundo zowonjezereka: Kugwiritsa ntchito mowa, mowa nthawi yaitali, msinkhu wa spiny neuron, nucleus accumbens, sucrose
Ndemanga: Klenowski PM, Shariff MR, Belmer A, Fogarty MJ, Mu EWH, Bellingham MC ndi Bartlett SE (2016) Kugwiritsa Ntchito kwa Sucrose kwa nthawi yaitali, Kuwongolera Morphology of Medium Spiny Neurons mu Nucleus Accumbens Shell. Kutsogolo. Behav. Neurosci. 10: 54. onetsani: 10.3389 / fnbeh.2016.00054
Adalandira: 03 December 2015; Yavomerezedwa: 07 March 2016;
Lofalitsidwa: 23 March 2016.
Lolembedwa ndi:
Djoher Nora Wopambana, Institute of Neurosciences de Bordeaux, France
Kuwunikira by:
Serge H. Ahmed, Center ya National de la Recherche Scientifique, France
Stéphanie Caille, Center ya National de la Recherche Scientifique, France
Copyright © 2016 Klenowski, Shariff, Belmer, Fogarty, Mu, Bellingham ndi Bartlett. Ichi ndi nkhani yotseguka yolumikizidwa pansi pa mawu a Malamulo a Creative Commons Licribution (CC BY). Kugwiritsiridwa ntchito, kufalitsa kapena kubereka m'mabwalo ena amavomerezedwa, kupatula ngati wolemba oyambirira kapena wothandizira chilolezo amavomerezedwa ndi kuti buku loyambirira m'magazini ino likutchulidwa, malinga ndi chizolowezi chophunzitsidwa. Palibe ntchito, kufalitsa kapena kubalana kumaloledwa zomwe sizikugwirizana ndi mawu awa.
* Zolemba: Anna E. Bartlett, [imelo ndiotetezedwa]