Te puru metilīni me ngā pūtau tautoko o te roro: ngā astrocyte, ngā microglia, me te mumura

Me whakaaro ka whakahaere koe i ngā whakamātau e rua ki te waikano puru kotahi, ā, ka puta he hua whakatenatena e rua. I tētahi ipu, ka ora ngā pūtau tautoko ā-whetū ahakoa te korenga o te hāora me te kūhuka. I tētahi atu, ka mau tonu te āhua marino, whai manga hoki o ngā pūtau ārai mate o te roro, ahakoa he tāoke huakita kei reira. He ngāwari te whakakotahi i ēnei hei whakapae kotahi: ka whakamauru te waikano i te mumura o te roro, ka tiaki hoki i te roro. Ko taua whakakotahitanga tonu te wāhi e tika ana kia tūpato te kaipānui.

E rua ngā kāhui pūtau tautoko o te roro, he rerekē ā rāua mahi, ā, he rerekē te whakaoho whakamātau e tūtaki ai ia kāhui ki te puru metilīni. He pūtau tautoko pākia ngā astrocyte. Kei waenga rātou i ngā ia toto me ngā pūtau io, ka tango i te glutamate tuwhene, ka whakarite i ngā taumata pāhare pāporo, ka penapena i te glycogen, ā, ka kawe i te wahie ki ngā pūtau io ina kaha ake te hiahia. Ko ngā microglia ngā kaitirotiro ārai mate e noho pūmau ana i reira. Ka tirotiro haere ō rātou toronga angiangi i te kiko, ka kite i ngā tohu huakita me ngā tohu wharanga, ā, ina puta he whakatūpato ka kukumea ngā toronga kia noho hei āhua porotaka, ā-amīpa, e pai ana mō te neke me te horomi, me te tuku anō i ngā rāpoi tuku tohu. Kāore te hua o tētahi kāhui e whakawhiti noa ki tērā atu, ā, mā te inenga i whakamahia i ia whakamātau e whakatau he aha rawa te mea i whakaaturia.

Ngā astrocyte i raro i te taumahatanga pākia: ko te wā te hua matua

Ka tīmata te whakamātau astrocyte ki te tango i ngā rawa e hiahiatia ana. I whakatipu ngā kairangahau i ngā astrocyte nō te kiri roro o ngā kiore kātahi anō ka whānau, ka tango i te kūhuka me te tata katoa o te hāora mō te ono hāora, kātahi ka whakahoki i ēnei e rua mō te rua tekau mā whā hāora. He tauira taiwhanga tēnei o te ikura roro me te hokinga o te rere toto i muri iho. I te wā i reira te puru metilīni i te wāhanga korenga, ka kino ake te oranga pūtau. I te wā i tāpirihia i te wāhanga whakahokinga hāora anake, ki te 0.1 me te 1 micromolar, ka tino pai ake te oranga e ai ki tētahi whakamātautau oranga pūtau mā te calcein. Ka pūrongo te rangahau astrocyte kiore i tēnei rerekētanga ā-wā, me ngā raraunga whakahā pūtau.

Ko taua rerekētanga te kitenga tino whai take. I te wāhanga korenga, tata tonu kāore he hāora hei tango i ngā irahiko, nō reira kāore he wāhi hei tuku mā te pūnaha kawe irahiko. I te wāhanga whakahokinga hāora, ka tīmata anō ngā pūnaha, ā, ka whai mahi te waikano. Ka pau i ngā astrocyte i whiwhi maimoatanga te hāora nui ake, ka kuhu mai te kūhuka nui ake, ka hangaia te ATP nui ake, ā, ka hangaia anō ngā putunga glycogen. Ka piki hoki te ngohe hexokinase, kāore hoki te superoxide mitokōria i piki. Ko te whakamārama e whakaarohia ana ko tērā e mōhiotia ana i te kōrero mō te puru metilīni hei kaikawe irahiko mitokōria: ka kawea ngā irahiko kia hipa i ngā wāhi kua aukatia i te mekameka whakahā, kia tīmata mā anō te whakahā, kaua ngā irahiko e turuturu ki ngā momo matū tauhohe.

Kia mārama ki te momo taunakitanga nei. He hua mō te oranga me te pākia i roto i tētahi momo pūtau motuhake kua wehea, me tētahi wā whai hua kua tautuhia (ko te whakaoranga, ehara i te korenga), me tētahi awhe kukūtanga kua tautuhia. Kāore tēnei e kōrero ana mō te tuku tohu ārai mate, mō te whanonga rānei.

Ngā microglia i raro i te whakatūpato huakita: kua whakaritea anō te pākia

Ka tīmata ngā whakamātau microglia i te whakaoho tauaro: ehara i te hemokai, engari he whakapokenga rūpahu. Ko te lipopolysaccharide, he wāhanga nō te kiriuhi o waho o te huakita, ka here ki ngā pūoko o te pūnaha ārai mate tūturu, ka mea ai ngā microglia kua tae mai ngā tukumate, ahakoa kāore he huakita ora i reira. I ngā kiore i hoatu ai te lipopolysaccharide, me tētahi aho pūtau microglia i whakatipuria, ka puta tētahi hōtaka mumura e mōhiotia ana: ka piki ngā matū whakakaha mumura, ka anga ngā microglia ki te āhua M1 pukuriri, ka mate ngā pūtau io e tata ana, ā, ka ngoikore ake ngā kararehe i ngā mahi ako me ngā mahi pūmahara.

Ka whai te rangahau kiore i tēnei urupare ki tētahi ara rongo hāora: ka whakakaha te lipopolysaccharide i te whakaputanga tuwhene o te PHD3, tētahi o ngā whākōkī prolyl hydroxylase e toru, mā tētahi mekameka Siah2/Morg1 kei mua i te ara. I taua wā tonu, ka whakaritea anō e ngā pūtau tā rātou whakamahi pūngao kia anga ki te glycolysis whai hāora, me te pikinga o ngā momo hāora tauhohe mitokōria. I ine tika ngā kaituhi i taua panonitanga mā ngā whakamātautau pākia Seahorse mō te whakamahinga hāora me te whakawaikawatanga o waho i te pūtau. Nā te puru metilīni i whakahuri te panonitanga pākia me te whakaputanga tuwhene o te PHD3, i whakaheke ngā matū mumura, i whakaiti te mate o ngā pūtau io, ā, i whakapai ngā kaute whanonga. I tāpiri te whakaahua paparanga tuku positron i tētahi taumata whakaahua: nā te lipopolysaccharide i whakapiki te kuhunga kūhuka ki te hippocampus i runga i te FDG-PET, ā, nā te maimoatanga i whakaheke anō. E hāngai ana tēnei ki te mārie ake o te pākia mumura i te roro ora.

He whānui ake tēnei huinga inenga i tō te rangahau astrocyte (ngā cytokine, te pākia, te whakaahua, me te whanonga kararehe), engari nō tētahi whakaoho kē, nō tētahi pūtau kē hoki. Me wehe tonu ngā whakaoho e te kaipānui e whakataurite ana i ēnei e rua: ka whakaora tētahi rangahau i ngā pūtau tautoko e hemokai ana i te wā whakaoranga; ka whakamauru tērā atu i te whakatūpato whakapokenga rūpahu i roto i ngā pūtau ārai mate.

Ngā microglia i raro i te karu whakarahi: ko te āhua hei inenga

Ka titiro tētahi whakamātau tuatoru ki taua whakatūpato huakita mā te āhua anake. I ngā ahurea pūtau glia nō te kiri roro o te kiore nui, he maha ngā toronga angiangi o ngā microglia mana kua waikanotia mō te tohu IBA1; koinei te āhua whai manga e tirotiro haere ana. Whai muri i te rua tekau mā whā hāora ki te lipopolysaccharide i te 10 micrograms per milliliter, ka papatahi ngā pūtau kia mau ki te āhua amīpa, ā, ka nui ake te horahanga o te tinana pūtau, me te āhua mau tonu o te paenga. Koinei te tohu āhuahanga o te porotakatanga. Nā te puru metilīni i te 1 micromolar, i hoatu ngātahitia me te tāoke, i pupuri ngā toronga whai manga, me te pupuri hoki i te horahanga tinana me te paenga kia tata ki ngā uara mana. Ka ine te rangahau ahurea pūtau kiore nui i tēnei whakaoranga āhua mā ngā inenga horahanga tinana pūtau me te paenga.

E rua ngā taipitopito e nui ake ai te uara o tēnei rangahau i tētahi pikitia noa. Tuatahi, kāore te matū whakataurite, te menadione, tētahi atu rāpoi whai ngohe hāoratanga-whakahekenga i taua kukūtanga tonu, i whakaora i te āhua. Ko taua matū anake hoki i pana i ngā pūtau kia anga ki te āhua kua whakahohetia. Nō reira, ehara tēnei pānga i te āhuatanga whānui o ngā matū katoa e huri haere ana i ngā tauhohenga hāoratanga-whakahekenga. Tuarua, ka hono ngā kaituhi i te pānga o te waikano ki te whakahohetanga Nrf2, he hōtaka tauwehe tuhi ira kei muri i ngā ira ārai hāoratanga, ārai mumura hoki, kaua ki te hopu tika i ngā matū tauhohe anake. Mā ngā kōrero e pā ana ki te hāoratanga-whakahekenga me te tuku tohu mumura e whakamārama te horopaki o tēnei hononga Nrf2.

Ahakoa rā, ko te āhua te mea iti rawa te hōhonutanga o ngā inenga e toru. I te nuinga o te wā, he pūtau tirotiro haere te pūtau whai manga, he pūtau kua whakahohetia te pūtau porotaka. Engari he tohu whakakapi noa te āhua, ehara i te tuhinga o ngā mahi. Kāore he pūtau ārai mate kawe-toto i tēnei ahurea, kāore he ara iahiko io, kāore hoki he putanga whanonga.

Te pānui taha ki te taha i ngā hua e toru

Ko te tauira puta noa i ngā rārangi, he inenga anō, he whakautu anō tō ia whakaoho. Ka whakautu te whakaoranga pākia i tētahi pātai pākia. Ka whakautu ngā raraunga cytokine me te whanonga i tētahi pātai mumura. Ka whakautu te āhua i tētahi pātai āhua. Kāore tētahi o ēnei e toru e whakawhiti takitahi ki tētahi atu.

Ngā mea kāore e whakatūturu ana ngā microglia e āhua marino ake ana

Koinei te rerenga kōrero e hiahiatia ana mō tēnei kaupapa katoa: ko ngā microglia e āhua iti ake ana te whakahohetanga, ko te pākia microglia kua panoni rānei, kāore ēnei e whakatūturu takitahi ana kua pai ake te mahi a te roro.

Ka taea te āhua te panoni me te kore e whai mai te mahi. Ka taea e tētahi pūtau te pupuri i ōna manga me te tuku tonu i ngā cytokine, te porotaka rānei i a ia e mahi ana i te mahi whai hua o te tango i ngā toenga. He rite tonu te herenga o ngā inenga pākia: ka whakaatu tētahi kauwhata Seahorse, tētahi matawai PET rānei, i te whakahaere pūngao, ehara i te hinengaro. He kaha ake te rangahau kiore i hono i ngā inenga pākia me ngā inenga āhua ki ngā whakamātau whanonga, nā te mea i whakapapa ngā taumata taunakitanga, kaua i tono mā te inenga kotahi e kawe te whakatau. Ahakoa i reira, ka mau tonu ngā herenga o mua, nā te mea he tauira te lipopolysaccharide o te whakatūpato kāore he tukumate ora, ehara i te whakapokenga tūturu; ehara ngā kiore i te tangata; ā, ka tohu ngā kaituhi ake i ngā rerekētanga i waenga i ngā momo. Me āta whakaaro te hunga e whakamahere ana i ngā mahi rangahau whai muri me pēhea te whakawhiti o ngā kitenga microglia i waenga i ngā tauira, i mua i te whakapae he ōrite te mahi a taua ara i roto i te kiko tangata.

Ka whai mai tētahi kōrero whai take mō te wā. Ka kino ake te hua astrocyte ina hoatu wawe, ā, ka pai ake ina hoatu i te wā whakaoranga. Ko ngā hua microglia nō te hoatutanga i te wā e tata ana ki te whakaoho mumura. I te ao tūturu, ka whakakotahi te wharanga roro i ēnei wāhanga e rua i te wā kotahi: te kore pūngao me te whakatūpato ārai mate, e whanake haere ana i roto i ngā hāora. Kāore e taea e tētahi whakamātau e wehe ana i tētahi wāhanga te whakatau i te wātaka mō te āhuatanga kua whakakotahitia. Nā reira ka wehe tonu ngā kōrerorero mō ngā wā hoatu i ngā wātaka o te korenga me te mumura.

Ka taea te whakarāpopototanga pono ki te kōwae kotahi. I roto i ngā astrocyte kua wehea, ka tīmata anō te puru metilīni i te whakahā, ka whakaora hoki i ngā pūtau, ina hoatu i te wā whakahokinga hāora. I roto i ngā microglia kua whakawerohia ki tētahi wāhanga huakita, ka whakahuri te puru metilīni i tētahi hōtaka pākia mumura mā tētahi ara PHD3 motuhake, ka pupuri hoki i te āhua whakatā. He tūturu ia hua i roto i tōna ake whakaritenga whakamātau, ā, kāore tētahi e noho hei whakatau whānui mō te mumura o te roro. He whai hua te whakataurite glia nā te mea ka aukati tonu i ngā kōrero e rua kia kore e hanumi hei kōrero kotahi.