Ubururu bwa methylene n'uturemangingo dufasha ubwonko: astrocytes, microglia, n'ububyimbirwe

Tekereza ukoze amagerageza abiri ukoresheje irangi rimwe ry'ubururu, ukabona ibisubizo bibiri bitanga icyizere. Mu gasahani kamwe, uturemangingo dufasha ubwonko tumeze nk'inyenyeri dukomeza kubaho nubwo tubuze ogisijeni na glukoze. Mu kandi, uturemangingo tw'ubudahangarwa bwo mu bwonko tugumana imiterere ituje ifite amashami nubwo duhuye n'uburozi bwa bagiteri. Biroroshye gushaka guhuza ibyo bisubizo byombi mu mwanzuro umwe: ko iryo rangi rigabanya ububyimbirwe mu bwonko kandi rikarinda ubwonko. Aho ni ho abasomyi bitonda bakwiye guhagarara bakabanza gushishoza.

Ubwonko bufite amatsinda abiri y'uturemangingo tubufasha, afite imirimo itandukanye, kandi ubururu bwa methylene bugeragezwa kuri buri tsinda hakoreshejwe imbarutso itandukanye. Astrocytes ni uturemangingo dushyigikira imikorere yo guhindura intungamubiri mo ingufu. Tuba hagati y'imiyoboro y'amaraso n'uturemangingo tw'imyakura, tukavanaho glutamate irenze ikenewe, tukaringaniza potasiyumu, tukabika glikojeni, kandi tukageza ibitanga ingufu ku turemangingo tw'imyakura igihe dukenera byinshi. Microglia ni uturemangingo tw'ubudahangarwa dusanzwe tuba mu bwonko kandi tukabugenzura. Udushami twatwo tworohereye tugenzura ingirangingo, tukamenya ibimenyetso bya bagiteri n'ibyangiritse. Iyo tubonye ikimenyetso cy'akaga, turikanya tukagira imiterere yiburungushuye imeze nka amibe, ibereye kwimuka no kumira ibindi bintu, kandi tukarekura molekile zitanga ibimenyetso. Igisubizo cyabonetse mu itsinda rimwe ntigihita kireba irindi, kandi igipimo cyakoreshejwe muri buri gerageza ni cyo kigena icyagaragajwe koko.

Astrocytes zibuze ibikenerwa mu mikorere: igihe ni cyo gisubizo cy'ingenzi

Igerageza kuri astrocytes ritangirira ku kuzima ibikenerwa. Abashakashatsi bakuriye muri laboratwari astrocytes zo mu gice cy'inyuma cy'ubwonko bw'imbeba nto zikivuka, bazikuraho glukoze na ogisijeni hafi ya yose mu gihe cy'amasaha atandatu, hanyuma babisubizaho byombi mu gihe cy'amasaha makumyabiri n'ane. Ubu ni uburyo bwa laboratwari bwo kwigana inkorora yo mu bwonko ikurikirwa no kongera gutembera kw'amaraso. Iyo ubururu bwa methylene bwabaga buhari mu gihe cyo kubura ibyo bikenerwa, uturemangingo twarushagaho gupfa. Iyo bwongerwagamo gusa mu gihe cyo kongera kubona ogisijeni, ku gipimo cya 0.1 na 1 micromolar, uturemangingo twakomeje kubaho twariyongeraga ku buryo bugaragara, nk'uko byapimwe n'ikizamini cya calcein cyo kureba niba uturemangingo tukiri tuzima. Ubushakashatsi kuri astrocytes z'imbeba nto bugaragaza iri tandukaniro rishingiye ku gihe hamwe n'amakuru ku guhumeka kw'uturemangingo.

Iryo tandukaniro ni cyo cyabonetse cy'ingenzi kurusha ibindi. Mu gihe cyo kubura ibikenerwa, ogisijeni yakira elegitoroni iba hafi ya ntayo, bityo uburyo bwo guhererekanya elegitoroni ntibugire aho buzigeza. Mu gihe cyo kongera kubona ogisijeni, imikorere y'uturemangingo irongera igatangira, irangi rikabona umurimo rikora. Astrocytes zahawe irangi zakoresheje ogisijeni nyinshi kurushaho, zinjiza glukoze nyinshi kurushaho, zikora ATP nyinshi kurushaho, kandi zongera kubika glikojeni. Imikorere ya hexokinase yariyongereye, ariko superoxide yo muri mitokondiriya ntiyiyongera. Ibisobanuro byatanzwe ni bya bindi bisanzwe biri mu nyandiko isobanura ubururu bwa methylene nk'umutwazi wa elegitoroni muri mitokondiriya: buhererekanya elegitoroni bukazinyuza ku mpande z'ahazibye mu ruhererekane rwo guhumeka, kugira ngo guhumeka byongere gutangira neza aho kugira ngo elegitoroni zimeneke zigakora molekile zikorana cyane n'izindi.

Zirikana ubwoko bw'ibimenyetso ubu bushakashatsi butanga. Ni igisubizo kijyanye no gukomeza kubaho no guhindura intungamubiri mo ingufu mu bwoko bumwe bw'uturemangingo bwatandukanyijwe n'ubundi, gifite igihe cyagaragajwe cyo kugira akamaro (mu gihe cyo kugarura imikorere, si mu gihe cyo kubura ibikenerwa) n'urugero rw'ubwinshi bw'irangi rwagaragajwe. Ntacyo kivuga ku kohereza ibimenyetso by'ubudahangarwa, kandi ntacyo kivuga ku myitwarire.

Microglia zahawe ikimenyetso cy'akaga ka bagiteri: imikorere yo kubona ingufu yarahinduwe

Amagerageza kuri microglia atangirira ku mbarutso inyuranye n'iyabanje: si ukubura intungamubiri, ahubwo ni ikimenyetso cy'ubwandu butariho. Lipopolysaccharide, igice cy'agahu k'inyuma ka bagiteri, ifata ku byakira ibimenyetso by'ubudahangarwa mvukanwa, igatuma microglia zifata ko ibitera indwara byahageze, nubwo nta bagiteri nzima zihari. Mu mbeba nto zahawe lipopolysaccharide no mu bwoko bw'uturemangingo twa microglia dukurirwa muri laboratwari, havamo imikorere isanzwe iranga ububyimbirwe: ibintu bitera ububyimbirwe biriyongera, microglia zikerekeza ku miterere ya M1 irangwa no kwibasira, uturemangingo tw'imyakura twegeranye na zo tugapfa, kandi inyamaswa zikagira amanota mabi kurushaho mu bizamini byo kwiga no kwibuka.

Ubushakashatsi ku mbeba nto bukurikirana iyi myitwarire bukayihuza n'inzira yumva urugero rwa ogisijeni: lipopolysaccharide ituma PHD3, imwe muri enzime eshatu za prolyl hydroxylase, ikorwa ku rugero rurengeje, binyuze mu ruhererekane rwa Siah2/Morg1 ruyibanziriza. Muri icyo gihe, uturemangingo duhindura uburyo dukoresha ingufu tukerekeza ku isenywa rya glukoze ribera ahari ogisijeni, hamwe no kwiyongera kwa molekile zishingiye kuri ogisijeni zikorana cyane n'izindi muri mitokondiriya. Abanditsi bapimye iryo hinduka mu buryo butaziguye bakoresheje ibizamini bya Seahorse bipima ikoreshwa rya ogisijeni n'iyiyongera ry'ubusharire hanze y'uturemangingo. Ubururu bwa methylene bwasubije inyuma iryo hinduka ry'imikorere yo kubona ingufu n'ikorwa rirengeje rya PHD3, bugabanya ibintu bitera ububyimbirwe, bugabanya impfu z'uturemangingo tw'imyakura, kandi butuma amanota y'ibizamini by'imyitwarire arushaho kuba meza. Gufata amashusho hakoreshejwe positron emission tomography byongeyeho ibindi bipimo: lipopolysaccharide yongereye glukoze yinjira muri hippocampus nk'uko byagaragajwe na FDG-PET, naho gutanga irangi bituma yongera kugabanuka. Ibyo bihuje n'imikorere yo kubona ingufu ijyanye n'ububyimbirwe yagabanutse mu bwonko bw'inyamaswa nzima.

Iri gerageza rifite ibipimo byinshi kurusha ubushakashatsi kuri astrocytes (cytokine, imikorere yo kubona ingufu, amashusho, n'imyitwarire y'inyamaswa), ariko rireba imbarutso itandukanye n'uturemangingo dutandukanye. Abasomyi bagereranya aya magerageza yombi bagomba kudahuza imbarutso zayo: ubushakashatsi bumwe bufasha uturemangingo dushyigikira ubwonko twabuze intungamubiri mu gihe cyo kugarura imikorere; ubundi bugabanya ikimenyetso cy'ubwandu butariho mu turemangingo tw'ubudahangarwa.

Microglia munsi ya mikorosikopi: imiterere nk'igipimo

Igerageza rya gatatu rireba icyo kimenyetso cy'akaga ka bagiteri rishingiye gusa ku miterere. Mu turemangingo twa glia two mu gice cy'inyuma cy'ubwonko bw'imbeba nini dukurirwa muri laboratwari, microglia z'itsinda ry'igereranya zasizwe irangi rigaragaza ikimenyetso cya IBA1 zigaragaza udushami twinshi tworohereye, ari yo miterere ifite amashami yo kugenzura. Nyuma y'amasaha makumyabiri n'ane ziri muri lipopolysaccharide ku gipimo cya 10 micrograms per milliliter, uturemangingo turambuka tukagira imiterere imeze nka amibe. Ubuso bw'igice nyamukuru cyatwo buriyongera, mu gihe uburebure bw'uruziga rugikikije buguma hafi uko bwari buri; ibyo ni ikimenyetso cya jewometiri cy'uko uturemangingo turi kwiburungushura. Ubururu bwa methylene ku gipimo cya 1 micromolar, bwatanzwe hamwe n'ubwo burozi, bwarinze udushami kandi butuma ubuso bw'igice nyamukuru n'uburebure bw'uruziga rugikikije biguma hafi y'ibipimo by'itsinda ry'igereranya. Ubushakashatsi ku turemangingo tw'imbeba nini dukurirwa muri laboratwari bupima uku kurindwa kw'imiterere bukoresheje ubuso bw'igice nyamukuru n'uburebure bw'uruziga rugikikije.

Ibintu bibiri bituma ubu bushakashatsi bugira agaciro karenze ako kwerekana ifoto gusa. Icya mbere, menadione yakoreshejwe mu kugereranya, indi molekile igira uruhare mu guhanahana elegitoroni ku gipimo kingana n'icy'irangi, ntiyarinze imiterere. Kandi iyo yakoreshwaga yonyine, yatumaga uturemangingo twerekeza ku miterere yo kuba twakanguwe. Bityo rero, iyi ngaruka si umwihariko rusange w'ibintu byose byinjira mu ruziga rwo guhanahana elegitoroni. Icya kabiri, abanditsi bahuza ingaruka y'irangi no gukangurwa kwa Nrf2, uburyo bugenzura iyandukurwa ry'amakuru y'uturemangingo kandi bugashyigikira ingirabuzima zirwanya iyangirika riterwa n'ikorwa rya ogisijeni n'ububyimbirwe, aho kubihuza gusa no gufata mu buryo butaziguye molekile zangiza. Izindi nyandiko ku guhanahana elegitoroni no ku bimenyetso by'ububyimbirwe zishyira iri sano rya Nrf2 mu mwanya waryo.

Ariko imiterere ni cyo gipimo gitanga ibimenyetso bike kurusha ibindi muri ibyo bitatu. Akaremangingo gafite amashami akenshi kaba kari kugenzura, naho akiburungushuye akenshi kaba kakanguwe, ariko imiterere ni ikimenyetso gifasha kugereranya, si inyandiko igaragaza imikorere yako. Utu turemangingo twakurirwaga muri laboratwari ntitwarimo uturemangingo tw'ubudahangarwa tuzanwa n'amaraso, nta miyoboro y'imikoranire y'uturemangingo tw'imyakura twarimo, kandi nta myitwarire twatangaga yo gupima.

Gusomera hamwe ibisubizo bitatu

Ikigaragara muri iyi mirongo ni uko buri mbarutso ifite igipimo cyayo n'igisubizo cyayo. Kugarura imikorere yo kubona ingufu bisubiza ikibazo kijyanye n'iyo mikorere. Amakuru kuri cytokine n'imyitwarire asubiza ikibazo kijyanye n'ububyimbirwe. Imiterere isubiza ikibazo kijyanye n'imiterere. Nta na kimwe muri ibyo bitatu gihita, cyonyine, gitanga umwanzuro ku kindi.

Ibyo microglia zigaragara nk'izituje kurushaho zitagaragaza

Iyi ni yo nteruro iyi ngingo yose ikeneye: kuba microglia zigaragara nk'izidakanguwe cyane, cyangwa imikorere yazo yo kubona ingufu yarahindutse, ntibigaragaza byonyine ko imikorere y'ubwonko yarushijeho kuba myiza.

Imiterere ishobora guhinduka imikorere ntihinduke. Akaremangingo gashobora kugumana amashami kako ariko kagakomeza kurekura cytokine, cyangwa kakiburungushura mu gihe kari gukora umurimo w'ingirakamaro wo gukuraho ibisigazwa. Ibipimo by'imikorere yo kubona ingufu bifite na byo iyo mbogamizi: igishushanyo cy'ibipimo bya Seahorse cyangwa ishusho ya PET byerekana uko ingufu zikoreshwa, si ubushobozi bwo gutekereza no gusobanukirwa. Ubushakashatsi ku mbeba nto bwahuje ibipimo by'imikorere yo kubona ingufu n'ibifitanye isano n'imiterere hamwe n'ibizamini by'imyitwarire burushaho gukomera, kubera ko bwakusanyije ibimenyetso byo ku nzego zitandukanye aho gusaba igipimo kimwe kwikorera umwanzuro wose. Ndetse no muri ubwo bushakashatsi, imbogamizi zisanzwe ziracyahari, kuko lipopolysaccharide yigana ikimenyetso cy'akaga kidaturuka ku bwandu buriho aho kwigana ubwandu nyakuri, imbeba nto si abantu, kandi abanditsi ubwabo bagaragaza itandukaniro hagati y'amoko y'ibinyabuzima. Umuntu wese uteganya ubushakashatsi bukurikira agomba gusuzuma uko ibyabonetse kuri microglia bishobora gukoreshwa mu buryo butandukanye bw'igerageza mbere yo kwemeza ko iyo nzira ikora kimwe no mu ngirangingo z'abantu.

Ibyo binatanga isomo rifatika ku gihe cyo gutanga irangi. Igisubizo kuri astrocytes cyerekana ingaruka mbi iyo irangi ritanzwe hakiri kare, n'ingaruka nziza iyo ritanzwe mu gihe cyo kugarura imikorere. Ibisubizo kuri microglia byaturutse ku gutanga irangi hafi y'igihe imbarutso y'ububyimbirwe yabereye. Gukomereka k'ubwonko mu buzima busanzwe kuvanga ibyo byiciro byombi icyarimwe: kubura ingufu no kwikanga kw'ubudahangarwa, bigenda bihinduka mu masaha. Igerageza ritandukanya icyiciro kimwe n'ibindi ntirishobora kugena gahunda yo gutanga irangi igihe byombi bihuriranye. Ni yo mpamvu ibiganiro ku bihe byo kuritanga bitandukanya igihe cyo kubura ibikenerwa n'igihe cy'ububyimbirwe.

Incamake ivuga ukuri yose yakwira mu gika kimwe. Muri astrocytes zatandukanyijwe n'utundi turemangingo, ubururu bwa methylene butanzwe mu gihe cyo kongera kubona ogisijeni butuma guhumeka byongera gutangira kandi bukarinda uturemangingo gupfa. Muri microglia zashyizwe imbere y'igice cya bagiteri, busubiza inyuma imikorere yo kubona ingufu ijyanye n'ububyimbirwe binyuze mu nzira yihariye ya PHD3, kandi bukarinda imiterere ituje. Buri gisubizo ni nyakuri mu buryo bw'igerageza cyabonetsemo, kandi nta na kimwe ari umwanzuro rusange ku bubyimbirwe mu bwonko. Kugereranya uturemangingo twa glia ni ingirakamaro kubera ko bibuza izi nkuru zombi kwivanga zigafatwa nk'imwe.