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Isidingo esikhulayo sokuxhumana ngocingo oluphathwayo siholele ekuveleni okuqhubekayo kobuchwepheshe obungenantambo (G), obungaba nemiphumela ehlukile ezinhlelweni zezinto eziphilayo. Ukuze sihlole lokhu, siveze amagundane ekuvezweni kwekhanda elilodwa ku-4G long-term evolution (LTE)-1800 MHz electromagnetic field (EMF) amahora ama-2. Sabe sesihlola umphumela we-lipopolysaccharide-induced acute neuroinflammation ekumbozweni kwendawo ye-microglia kanye nomsebenzi we-electrophysiological neuronal ku-primary auditory cortex (ACx). Isilinganiso se-SAR ku-ACx singu-0.5 W/kg. Ukuqoshwa kwamayunithi amaningi kukhombisa ukuthi i-LTE-EMF ibangela ukwehla kobukhulu bempendulo kumathoni amsulwa kanye nokuzwakala kwemvelo, kuyilapho ukwanda komkhawulo we-acoustic wamaza aphansi naphakathi. I-Iba1 immunohistochemistry ayibonisanga zinguquko endaweni embozwe yimizimba ye-microglial kanye nezinqubo. Kumagundane aphilile, ukuvezwa okufanayo kwe-LTE akuzange kubangele izinguquko ekujuleni kokuphendula kanye nemingcele ye-acoustic. Idatha yethu ikhombisa ukuthi ukuvuvukala kwe-acute neuroinflammation kuzwela ama-neurons ku-LTE-EMF, okuholele ekucutshungulweni okushintshiwe kwe-acoustic stimuli ku-ACx.
Indawo ye-electromagnetic yesintu ishintshe kakhulu eminyakeni engamashumi amathathu edlule ngenxa yokwanda okuqhubekayo kokuxhumana okungenantambo. Njengamanje, abantu abangaphezu kwezingxenye ezimbili kwezintathu babhekwa njengabasebenzisi befoni ephathekayo (MP). Ukusabalala okukhulu kwalolu buchwepheshe kubangele ukukhathazeka kanye nempikiswano mayelana nemiphumela engaba yingozi yamasimu kagesi aqhutshwayo (ama-EMF) ebangeni lemvamisa yomsakazo (RF), akhishwa yi-MP noma iziteshi eziyisisekelo futhi afake ikhodi yokuxhumana. Le nkinga yezempilo yomphakathi iphefumulele izifundo eziningi zokuhlola ezizinikele ekuphenyeni imiphumela yokumuncwa kwemvamisa yomsakazo ezicutshini zebhayoloji. Ezinye zalezi zifundo zibheke izinguquko emsebenzini wenethiwekhi ye-neuronal kanye nezinqubo zokuqonda, ngenxa yokusondela kobuchopho emithonjeni ye-RF ngaphansi kokusetshenziswa kabanzi kwe-MP. Izifundo eziningi ezibikiwe zibhekana nemiphumela yezimpawu eziguquliwe ze-pulse ezisetshenziswa ohlelweni lomhlaba wonke lwesizukulwane sesibili (2G) lwezokuxhumana zeselula (GSM) noma i-wideband code division multiple access (WCDMA)/izinhlelo zokuxhumana zeselula zesizukulwane sesithathu (WCDMA/3G UMTS)2,3,4,5.Kuncane okwaziwayo ngemiphumela yezimpawu zemvamisa yomsakazo ezisetshenziswa kumasevisi eselula esizukulwane sesine (4G), ancike ku- ubuchwepheshe be-inthanethi obusebenzisa yonke idijithali obubizwa ngokuthi ubuchwepheshe be-Long Term Evolution (LTE). Okwethulwe ngo-2011, insizakalo ye-handset ye-LTE kulindeleke ukuthi ifinyelele ababhalisile be-LTE emhlabeni wonke abayizigidigidi ezingu-6.6 ngoJanuwari 2022 (GSMA: //gsacom.com). Uma kuqhathaniswa nezinhlelo ze-GSM (2G) kanye ne-WCDMA (3G) ezisekelwe ezinhlelweni zokushintshashintsha kwenethiwekhi eyodwa, i-LTE isebenzisa i-Orthogonal Frequency Division Multiplexing (OFDM) njengefomethi yesignali eyisisekelo.6. Emhlabeni wonke, izinsizakalo zeselula ze-LTE zisebenzisa uhla lwamabhendi emvamisa ahlukene phakathi kuka-450 no-3700 MHz, kufaka phakathi amabhendi angu-900 no-1800 MHz nawo asetshenziswa ku-GSM.
Amandla okuchayeka kwe-RF ekuthinteni izinqubo zebhayoloji anqunywa kakhulu yizinga elithile lokumuncwa (i-SAR) elivezwa ku-W/kg, elilinganisa amandla amuncwa ezicutshini zebhayoloji. Imiphumela yokuchayeka ekhanda okubukhali kwemizuzu engama-30 kumasignali e-2.573 GHz LTE emsebenzini wenethiwekhi ye-neuronal yomhlaba wonke ihlolwe muva nje kubantu abazinikele abaphilile. Kusetshenziswa i-fMRI yesimo sokuphumula, kwabonwa ukuthi ukuchayeka kwe-LTE kungadala ukuguquguquka kwemvamisa okuhamba kancane kanye noshintsho ekuxhumekeni kwangaphakathi noma phakathi kwezifunda, kuyilapho amazinga e-SAR aphezulu ngokwendawo angaphezu kwama-10 g ezicubu kulinganiselwa ukuthi ayahluka phakathi kuka-0.42 no-1.52 W/ kg, ngokusho kwezihloko 7, 8, 9. Ukuhlaziywa kwe-EEG ngaphansi kwezimo ezifanayo zokuchayeka (ubude bemizuzu engama-30, izinga le-SAR eliphakeme elilinganisiwe elingu-1.34 W/kg kusetshenziswa imodeli yekhanda lomuntu emele) kubonise amandla anciphile e-spectral kanye nokuhambisana kwe-hemispheric kuma-alpha nama-beta band. Kodwa-ke, ezinye izifundo ezimbili ezisekelwe ekuhlaziyweni kwe-EEG zithole ukuthi imizuzu engama-20 noma engama-30 yokuchayeka ekhanda le-LTE, kanye namazinga aphezulu e-SAR endawo abekwe cishe ku-2 W/kg, noma ngabe ayengenawo. umphumela obonakalayo11 noma oholele ekutheni amandla e-spectral ku-alpha band ehle, kuyilapho ukuqonda kungazange kushintshe ekusebenzeni okuhlolwe ngokuhlolwa kwe-Stroop 12. Umehluko omkhulu utholakale nasemiphumeleni ye-EEG noma izifundo zokuqonda ezibheka ngqo imiphumela yokuvezwa kwe-GSM noma i-UMTS EMF. Kucatshangwa ukuthi kuvela ekuhlukeni kokuklama indlela kanye nemingcele yokuhlola, kufaka phakathi uhlobo lwesignali kanye nokuguquguquka, ukuqina kokuvezwa kanye nobude besikhathi, noma kusuka ekuhlukeni kwabantu maqondana nobudala, i-anatomy, noma ubulili.
Kuze kube manje, zimbalwa izifundo zezilwane ezisetshenzisiwe ukuthola ukuthi ukuchayeka ku-LTE signaling kuthinta kanjani ukusebenza kobuchopho. Muva nje kubikwe ukuthi ukuchayeka ohlelweni lwezimpuku ezisakhula kusukela esigabeni sokuphela kwengane kuya ekunceliseni (imizuzu engama-30 ngosuku, izinsuku ezi-5/ngesonto, nge-SAR yomzimba wonke engu-0.5 noma i-1 W/kg) kuholele ekushintsheni kokuziphatha kwemisipha kanye nesifiso sokudla lapho umuntu esekhulile 14. Ukuchayeka ohlelweni okuphindaphindiwe (amahektha ama-2 ngosuku amasonto ayi-6) kumagundane amadala kutholakale ukuthi kubangela ukucindezeleka kwe-oxidative futhi kunciphisa ubukhulu bamandla abonakalayo atholakala kumthambo we-optic, nge-SAR ephezulu elinganiselwa ukuthi iphansi njenge-10 mW/kg15.
Ngaphezu kokuhlaziywa ezikalini eziningi, kufaka phakathi amazinga eseli kanye nama-molecule, amamodeli egundane angasetshenziswa ukutadisha imiphumela yokuchayeka kwe-RF ngesikhathi sesifo, njengoba bekugxilwe ngaphambili ku-GSM noma i-WCDMA/3G UMTS EMF kumongo wokuvuvukala kwe-neuroinflammation okubukhali. Izifundo zibonise imiphumela yokuxhuzula, izifo ze-neurodegenerative noma i-gliomas 16,17,18,19,20.
Amagundane ajovwe yi-Lipopolysaccharide (LPS) ayimodeli yangaphambilini yokusabela okubukhali kokuvuvukala kwemizwa okuhlobene nezifo ezithathelwanayo ezingelapheki ezibangelwa amagciwane noma amabhaktheriya athinta iningi labantu minyaka yonke. Lesi simo sokuvuvukala siholela esifweni esiphendukayo kanye nesifo sokucindezeleka esibonakaliswa umkhuhlane, ukulahlekelwa yisifiso sokudla, kanye nokunciphisa ukuxhumana nabantu. Ama-phagocyte e-CNS ahlala njenge-microglia angamaseli abalulekile asebenzayo ale mpendulo yokuvuvukala kwemizwa. Ukwelashwa kwamagundane nge-LPS kubangela ukusebenza kwe-microglia okubonakala ngokushintsha isimo sawo kanye nezinqubo zamaseli kanye nezinguquko ezijulile kuphrofayili ye-transcriptome, kufaka phakathi ukwanda kwezakhi zofuzo ezifaka ama-cytokine noma ama-enzyme abangela ukuvuvukala, athinta amanethiwekhi e-neuronal Imisebenzi 22, 23, 24.
Sifunda imiphumela yokuchayeka kwekhanda elilodwa kwamahora ama-2 ku-GSM-1800 MHz EMF kumagundane aphathwe i-LPS, sithole ukuthi ukusayinwa kwe-GSM kubangela izimpendulo zamaseli ku-cortex yobuchopho, okuthinta ukubonakaliswa kwezakhi zofuzo, i-glutamate receptor phosphorylation, i-neuronal Meta-evoked firing kanye ne-morphology ye-microglia ku-cortex yobuchopho. Le miphumela ayitholakalanga kumagundane aphilile athole ukuchayeka okufanayo kwe-GSM, okuphakamisa ukuthi isimo se-neuroinflammatory esibangelwa yi-LPS senza amaseli e-CNS azwele ekusayinweni kwe-GSM. Sigxile ku-cortex yokuzwa (ACx) yamagundane aphathwe i-LPS, lapho i-SAR yendawo yayilinganiselwa ku-1.55 W/kg, sabona ukuthi ukuchayeka kwe-GSM kuholele ekwandeni kobude noma ukuhlangana kwezinqubo ze-microglial kanye nokwehla kwezimpendulo ze-neuronal ezibangelwa amathoni amsulwa kanye ne-.Natural Stimulation 28.
Esifundweni samanje, sihlose ukuhlola ukuthi ukuchayeka ekhanda kuphela ezimpawini ze-LTE-1800 MHz kungashintsha yini isimo se-microglial kanye nomsebenzi we-neuronal ku-ACx, kunciphisa amandla okuchayeka ngezingxenye ezimbili kwezintathu. Sibonisa lapha ukuthi ukuchayeka kwe-LTE akuzange kube nomthelela ezinqubweni ze-microglial kodwa kusabangele ukwehla okukhulu komsebenzi we-cortical ovuswa umsindo ku-ACx yamagundane aphathwe yi-LPS anenani le-SAR elingu-0.5 W/kg.
Njengoba sinikezwe ubufakazi bangaphambilini bokuthi ukuchayeka ku-GSM-1800 MHz kushintshe isimo se-microglial ngaphansi kwezimo ezibangela ukuvuvukala, sihlole lo mphumela ngemuva kokuchayeka ekusayinweni kwe-LTE.
Amagundane amadala ajovwa nge-LPS amahora angama-24 ngaphambi kokuvezwa nge-sham ekhanda kuphela noma ukuvezwa ku-LTE-1800 MHz. Lapho evezwa, izimpendulo ze-neuroinflammatory ezibangelwa yi-LPS zasungulwa ku-cortex yobuchopho, njengoba kuboniswe ukwanda kwezakhi zofuzo ezibangela ukuvuvukala kanye nezinguquko ekubunjweni kwe-cortical microglia (Isithombe 1). Amandla avezwa yikhanda le-LTE abekwe ukuze athole izinga elimaphakathi le-SAR elingu-0.5 W/kg ku-ACx (Isithombe 2). Ukuze sinqume ukuthi i-microglia esebenzayo ye-LPS iyasabela yini ku-LTE EMF, sihlaziye izingxenye ze-cortical ezifakwe i-anti-Iba1 eziqoshwe ngokukhetha la maseli. Njengoba kuboniswe ku-Figure 3a, ezigabeni ze-ACx ezilungisiwe emahoreni ama-3 kuya kwangama-4 ngemuva kokuvezwa nge-sham noma i-LTE, i-microglia ibukeka ifana kakhulu, ikhombisa ukwakheka kweseli "okufana nobukhulu" okubangelwa ukwelashwa kwe-LPS okubangela ukuvuvukala (Isithombe 1). Ngokuhambisana nokungabikho kwezimpendulo ze-morphological, ukuhlaziywa kwesithombe sobuningi kwembula ukuthi akukho mehluko obalulekile endaweni iyonke (ukuhlolwa kwe-t okungabhangqiwe, p = 0.308) noma indawo (p = 0.196) kanye nobuningi (p = 0.061) bokusabela komzimba kwe-Iba1 uma kuqhathaniswa ukuchayeka emizimbeni yamaseli anebala le-Iba 1 kumagundane e-LTE uma kuqhathaniswa nezilwane ezivezwe mbumbulu (Isithombe 3b-d).
Imiphumela yomjovo we-LPS ip ku-cortical microglia morphology. Umbono omele i-microglia engxenyeni ye-coronal ye-cerebral cortex (isifunda se-dorsomedial) amahora angama-24 ngemuva komjovo we-LPS noma imoto (ukulawula) ngaphakathi kwe-peritoneal. Amaseli afakwe i-anti-Iba1 antibody njengoba kuchaziwe ngaphambilini. Ukwelashwa kwe-LPS okukhuthaza ukuvuvukala kuholele ekushintsheni ku-morphology ye-microglia, kufaka phakathi ukuqina kwe-proximal kanye nokwanda kwamagatsha amafushane esibili ezinqubo zamaseli, okuholele ekubukekeni "okufana nobukhulu". Ibha yesikali: 20 µm.
Ukuhlaziywa kwe-Dosimetric kwesilinganiso sokumuncwa esithile (i-SAR) ebuchosheni begundane ngesikhathi sokuchayeka ku-1800 MHz LTE. Imodeli ehluke kakhulu echazwe ngaphambilini yegundane eliphanayo kanye ne-antenna ye-loop62 yasetshenziswa ukuhlola i-SAR yendawo ebuchosheni, ngegridi ye-cubic engu-0.5 mm3.(a) Umbono womhlaba wonke wemodeli yegundane endaweni yokuchayeka ene-antenna ye-loop ngaphezulu kwekhanda kanye nephedi yokushisa yensimbi (ephuzi) ngaphansi komzimba.(b) Ukusatshalaliswa kwamanani e-SAR ebuchosheni bomuntu omdala kusisombululo sendawo esingu-0.5 mm3. Indawo ehlukaniswe uhlaka olumnyama esigabeni se-sagittal ihambelana ne-cortex eyinhloko yokuzwa lapho kuhlaziywa khona umsebenzi we-microglial kanye ne-neuronal. Isikali esinemibala samanani e-SAR sisebenza kuzo zonke izibalo eziboniswe esithombeni.
I-microglia efakwe i-LPS ku-cortex ye-auditory yegundane ngemuva kokuvezwa yi-LTE noma i-Sham.(a) Umbono omele ohlanganisiwe we-microglia efakwe i-anti-Iba1 antibody ezingxenyeni ze-coronal ze-LPS-perfused rat auditory cortex emahoreni ama-3 kuya kwangama-4 ngemuva kokuvezwa yi-Sham noma i-LTE (ukuvezwa). Ibha yesikali: 20 µm.(bd) Ukuhlolwa kwe-morphometric kwe-microglia emahoreni ama-3 kuya kwangama-4 ngemuva kokuvezwa yi-sham (amachashazi avulekile) noma ukuvezwa yi-LTE (amachashazi amnyama avele obala).(b, c) Ukumbozwa kwendawo (b) kophawu lwe-microglia i-Iba1 kanye nezindawo zemizimba yamaseli e-Iba1-positive (c). Idatha imele indawo yokudaya i-anti-Iba1 ebekwe ngendlela evamile ibe yisilinganiso esivela ezilwaneni ezivezwe yi-Sham.(d) Inani lemizimba yamaseli e-microglial avele obala i-anti-Iba1. Umehluko phakathi kwezilwane ze-Sham (n = 5) kanye ne-LTE (n = 6) wawungabalulekile (p > 0.05, i-t-test engabhangqiwe). Phezulu naphansi kwebhokisi, imigqa ephezulu nephansi imelela Iphesenti lama-25-75 kanye nephesenti lama-5-95 ngokulandelana. Inani elimaphakathi limakwe ngokubomvu ebhokisini.
Ithebula 1 lifingqa izinombolo zezilwane kanye nokuqoshwa kwamayunithi amaningi okutholwe ku-cortex eyinhloko yokuzwa yamaqembu amane amagundane (i-Sham, i-Exposed, i-Sham-LPS, i-Exposed-LPS). Emiphumeleni engezansi, sifaka konke ukuqoshwa okubonisa insimu yokwamukela yesikhashana ye-spectral ebalulekile (i-STRF), okungukuthi, izimpendulo ezivuswe yithoni okungenani ukuphambuka okujwayelekile okungu-6 okuphezulu kunezinga lokudubula okuzenzakalelayo (bheka Ithebula 1). Sisebenzisa le nqubo, sikhethe amarekhodi angu-266 eqembu le-Sham, amarekhodi angu-273 eqembu le-Exposed, amarekhodi angu-299 eqembu le-Sham-LPS, kanye namarekhodi angu-295 eqembu le-Exposed-LPS.
Ezigabeni ezilandelayo, sizoqala ngokuchaza amapharamitha akhishwe ensimini yokwamukela ye-spectral-temporal (okungukuthi, impendulo kumathoni amsulwa) kanye nempendulo ekukhulumeni kwezwi elithile le-xenogeneic. Sizobe sesichaza ukulinganiswa kwendawo yempendulo yemvamisa etholwe eqenjini ngalinye. Uma sicabangela ukuba khona "kwedatha ehlanganisiwe"30 ekwakhiweni kwethu kokuhlola, konke ukuhlaziywa kwezibalo kwenziwe ngokusekelwe enanini lezikhundla ku-electrode array (umugqa wokugcina kuThebula 1), kodwa yonke imiphumela echazwe ngezansi nayo isekelwe enanini lezikhundla eqenjini ngalinye. Inani eliphelele lokuqoshwa kwamayunithi amaningi okuqoqwe (umugqa wesithathu kuThebula 1).
Isibalo 4a sibonisa ukusatshalaliswa kwemvamisa okulungile (i-BF, okuveza impendulo ephezulu ku-75 dB SPL) yama-cortical neurons atholwe ku-Sham ephathwe yi-LPS kanye nezilwane eziveziwe. Ububanzi bemvamisa ye-BF kuwo womabili amaqembu banwetshwe kusukela ku-1 kHz kuya ku-36 kHz. Ukuhlaziywa kwezibalo kubonise ukuthi lokhu kusatshalaliswa kwakufana (i-chi-square, p = 0.278), okuphakamisa ukuthi ukuqhathanisa phakathi kwamaqembu amabili kungenziwa ngaphandle kokukhetha isampula.
Imiphumela yokuchayeka kwe-LTE kumapharamitha alinganisiwe ezimpendulo ze-cortical ezilwaneni eziphathwe yi-LPS.(a) Ukusatshalaliswa kwe-BF kuma-neuron e-cortical ezilwane eziphathwe yi-LPS ezivezwe ku-LTE (emnyama) kanye ne-sham-exposed ku-LTE (emhlophe). Akukho mehluko phakathi kokusatshalaliswa okubili.(bf) Umphumela wokuchayeka kwe-LTE kumapharamitha alinganisa insimu yokwamukela ye-spectral temporal (STRF). Amandla okuphendula ancishiswe kakhulu (*p < 0.05, i-t-test engabhangqiwe) kuzo zombili i-STRF (amandla okuphendula aphelele) kanye nama-frequency afanele (b,c). Ubude besikhathi sempendulo, i-bandwidth yokuphendula, kanye ne-bandwidth constant (df). Kokubili amandla kanye nokuthembeka kwesikhashana kwezimpendulo ekukhulumeni kwezwi kuncishisiwe (g, h). Umsebenzi ozenzakalelayo awuncishiswanga kakhulu (i).(*p < 0.05, i-t-test engabhangqiwe).(j,k) Imiphumela yokuchayeka kwe-LTE kuma-cortical thresholds. Izilinganiso ezimaphakathi zaziphezulu kakhulu kumagundane atholakale yi-LTE uma kuqhathaniswa namagundane atholakale yi-sham. Lo mphumela ubonakala kakhulu kuma-frequency aphansi naphakathi.
Izibalo 4b-f zibonisa ukusatshalaliswa kwamapharamitha atholakala ku-STRF yalezi zilwane (izindlela ezikhonjiswe ngemigqa ebomvu). Imiphumela yokuchayeka kwe-LTE ezilwaneni eziphathwe nge-LPS ibonakala ikhombisa ukwehla kokujabula kwe-neuronal. Okokuqala, ukuqina kokuphendula kanye nezimpendulo kwakuphansi kakhulu ku-BF uma kuqhathaniswa nezilwane ze-Sham-LPS (Isithombe 4b,c unpaired t-test, p = 0.0017; kanye no-p = 0.0445). Ngokufanayo, izimpendulo emisindweni yokuxhumana zehle kokubili emandleni okuphendula kanye nokuthembeka phakathi kwesilingo (Isithombe 4g,h; unpaired t-test, p = 0.043). Umsebenzi ozenzakalelayo wehlisiwe, kodwa lo mphumela wawungabalulekile (Isithombe 4i; p = 0.0745). Ubude bempendulo, umkhawulokudonsa wokulungisa, kanye nokubambezeleka kokuphendula akuzange kuthinteke ukuchayeka kwe-LTE ezilwaneni eziphathwe nge-LPS (Isithombe 4d-f), okubonisa ukuthi ukukhetha imvamisa kanye nokunemba kwezimpendulo zokuqala akuzange kuthinteke ukuchayeka kwe-LTE ezilwaneni eziphathwe nge-LPS.
Ngokulandelayo sihlole ukuthi ngabe imingcele ye-cortical yethoni emsulwa ishintshiwe yini ngokuvezwa kwe-LTE. Kusukela endaweni yokuphendula imvamisa (i-FRA) etholwe ekurekhodweni ngakunye, sinqume imingcele yokuzwa yemvamisa ngayinye futhi salinganisa le mingcele yamaqembu womabili ezilwane.Isithombe 4j sibonisa imingcele ephakathi (± sem) kusukela ku-1.1 kuya ku-36 kHz kumagundane aphathwe yi-LPS.Ukuqhathanisa imingcele yokuzwa yamaqembu e-Sham kanye ne-Exposed kubonise ukwanda okukhulu kwemingcele ezilwaneni eziveziwe uma kuqhathaniswa nezilwane ze-Sham (Isithombe 4j), umphumela owawubonakala kakhulu kuma-frequency aphansi naphakathi.Ngokuqondile, kuma-frequency aphansi (< 2.25 kHz), isilinganiso sama-neurons e-A1 anomkhawulo ophezulu sanda, kuyilapho isilinganiso sama-neurons aphansi naphakathi nomkhawulo sehla (i-chi-square = 43.85; p < 0.0001; Isithombe 4k, kwesobunxele Isibalo) . Umphumela ofanayo ubonwe kuma-mid-frequency (2.25 < Freq(kHz) < 11): ingxenye ephezulu yokuqoshwa kwe-cortical ene-intermediate threshold kanye nengxenye encane yama-neurons ane-low thresholds uma kuqhathaniswa neqembu elingadalulwanga (Chi - Square = 71.17; p < 0.001; Umfanekiso 4k, iphaneli eliphakathi). Kwakukhona nomehluko obalulekile ku-threshold yama-neuron ane-high-frequency (≥ 11 kHz, p = 0.0059); ingxenye yama-neurons ane-low-threshold yehlile kanti ingxenye yo-mid-high threshold yanda (chi-square = 10.853; p = 0.04 Umfanekiso 4k, iphaneli elingakwesokudla).
Isibalo 5a sibonisa ukusatshalaliswa kwemvamisa okuhle kakhulu (i-BF, okuphakamisa impendulo ephezulu ku-75 dB SPL) yama-neuron e-cortical atholwe ezilwaneni ezinempilo zamaqembu e-Sham kanye ne-Exposed. Ukuhlaziywa kwezibalo kubonise ukuthi ukusatshalaliswa okubili kwakufana (i-chi-square, p = 0.157), okuphakamisa ukuthi ukuqhathanisa phakathi kwamaqembu amabili kungenziwa ngaphandle kokukhetha isampula.
Imiphumela yokuvezwa kwe-LTE kumapharamitha alinganisiwe ezimpendulo ze-cortical ezilwaneni eziphilile.(a) Ukusatshalaliswa kwe-BF kuma-neuron e-cortical ezilwane eziphilile ezivezwe ku-LTE (oluhlaza okwesibhakabhaka okumnyama) kanye ne-sham-exposed ku-LTE (oluhlaza okwesibhakabhaka okukhanyayo). Akukho mehluko phakathi kokusabalalisa okubili.(bf) Umphumela wokuvezwa kwe-LTE kumapharamitha alinganisa insimu yokwamukela ye-spectral temporal (STRF). Akukho shintsho oluphawulekayo ekujuleni kokuphendula kulo lonke i-STRF kanye nama-frequency afanele (b, c). Kukhona ukwanda okuncane kwesikhathi sokuphendula (d), kodwa akukho shintsho ku-bandwidth yokuphendula kanye ne-bandwidth (e, f). Amandla noma ukuthembeka kwesikhashana kwezimpendulo ekukhulumeni kwamagama akushintshile (g, h). Akukho shintsho oluphawulekayo emsebenzini ozenzakalelayo (i).(*p < 0.05 unpaired t-test).(j,k) Imiphumela yokuvezwa kwe-LTE kuma-threshold e-cortical. Ngokwesilinganiso, ama-threshold awazange ashintshe kakhulu kumagundane avezwe yi-LTE uma kuqhathaniswa namagundane avezwe yi-Sham, kodwa ama-threshold aphezulu ama-frequency ayephansi kancane ezilwaneni ezivezwe.
Izibalo 5b-f zibonisa amabhokisi abonisa ukusatshalaliswa kanye nesilinganiso (umugqa obomvu) wamapharamitha athathwe kumasethi amabili e-STRF. Ezilwaneni ezinempilo, ukuvezwa kwe-LTE ngokwako kube nomthelela omncane enanini eliphakathi lamapharamitha e-STRF. Uma kuqhathaniswa neqembu le-Sham (amabhokisi akhanyayo vs aluhlaza okwesibhakabhaka amnyama eqenjini eliveziwe), ukuvezwa kwe-LTE akuzange kushintshe ubukhali bempendulo iyonke noma impendulo ye-BF (Umfanekiso 5b, c; ukuhlolwa kwe-t okungabhangqiwe, p = 0.2176, kanye no-p = 0.8696 ngokulandelana). Futhi akukho mphumela kububanzi be-spectral kanye nokubambezeleka (p = 0.6764 kanye no-p = 0.7129, ngokulandelana), kodwa kube nokwanda okukhulu kwesikhathi sokuphendula (p = 0.047). Futhi akukho mphumela emandleni ezimpendulo zokubiza (Umfanekiso 5g, p = 0.4375), ukuthembeka phakathi kwezilingo zalezi zimpendulo (Umfanekiso 5h, p = 0.3412), kanye nomsebenzi ozenzakalelayo (Umfanekiso 5).5i; p = 0.3256).
Isithombe 5j sibonisa imingcele ephakathi (± sem) kusukela ku-1.1 kuya ku-36 kHz kumagundane anempilo. Asizange sibonise umehluko omkhulu phakathi kwamagundane angcolile namagundane abonakalayo, ngaphandle komkhawulo ophansi kancane ezilwaneni ezivezwe kumaza aphezulu (11–36 kHz) (ukuhlolwa kwe-t okungabhangqiwe, p = 0.0083). Lo mphumela ubonisa iqiniso lokuthi ezilwaneni ezivezwe, kulolu hlu lwemvamisa (chi-square = 18.312, p = 0.001; Isithombe 5k), kwakukhona ama-neurons amaningi kancane anemingcele ephansi nephakathi (ngenkathi imingcele ephezulu) ama-neurons ambalwa).
Ekuphetheni, lapho izilwane eziphilile zivezwa ku-LTE, kwakungekho mthelela emandleni okuphendula emisindo emsulwa kanye nemisindo eyinkimbinkimbi njengokukhala. Ngaphezu kwalokho, ezilwaneni ezinempilo, imingcele yokuzwa kwe-cortical yayifana phakathi kwezilwane ezivezwe kanye nezilwane ezingamanga, kanti ezilwaneni eziphathwe yi-LPS, ukuvezwa kwe-LTE kuholele ekwandeni okukhulu kwemingcele ye-cortical, ikakhulukazi ebangeni eliphansi neliphakathi.
Ucwaningo lwethu lukhombisile ukuthi kumagundane amadala amaduna abhekene nokuvuvukala okukhulu kwe-neuroinflammation, ukuchayeka ku-LTE-1800 MHz ene-SARACx yendawo engu-0.5 W/kg (bheka Izindlela) kuholele ekunciphiseni okukhulu kobukhulu bezimpendulo ezivuswa umsindo ekuqopheni okuyinhloko kokuxhumana. Lezi zinguquko emsebenzini we-neuronal zenzeke ngaphandle koshintsho olubonakalayo ebangeni lendawo embozwe yizinqubo ze-microglial. Lo mphumela we-LTE ekuqineni kwezimpendulo ezivuswa yi-cortical awuzange ubonwe kumagundane anempilo. Uma sicabangela ukufana kokusatshalaliswa kwemvamisa okulungile phakathi kwamayunithi okurekhoda ezilwaneni ezivezwe yi-LTE nezivezwe yi-sham, umehluko ekusebenzeni kwe-neuronal ungabangelwa yimiphumela yezinto eziphilayo zezibonakaliso ze-LTE kunokukhetha isampula (Isithombe 4a). Ngaphezu kwalokho, ukungabikho kwezinguquko ekubambezelekeni kokuphendula kanye ne-bandwidth yokulungisa i-spectral kumagundane avezwe yi-LTE kusikisela ukuthi, cishe, lokhu kuqoshwa kwathathwa amasampula kusuka ezingqimbeni ezifanayo ze-cortical, ezitholakala ku-ACx eyinhloko kunezifunda zesibili.
Ngokwazi kwethu, umphumela wokubonisana kwe-LTE ezimpendulweni ze-neuronal awukaze ubikwe ngaphambilini. Kodwa-ke, izifundo zangaphambilini zibhale ikhono le-GSM-1800 MHz noma i-1800 MHz continuous wave (CW) lokushintsha ukujabula kwe-neuronal, yize kunomehluko omkhulu kuye ngendlela yokuhlola. Ngemva nje kokuchayeka ku-1800 MHz CW ezingeni le-SAR elingu-8.2 W/Kg, ukuqoshwa okuvela ku-snail ganglia kubonise ukwehla kwemingcele yokuqalisa amandla esenzo kanye nokuguqulwa kwe-neuronal. Ngakolunye uhlangothi, umsebenzi wokubhoboza nokuqhuma kwamasiko e-neuronal ayisisekelo avela ebuchosheni begundane wehlisiwe ngokuchayeka ku-GSM-1800 MHz noma i-1800 MHz CW imizuzu eyi-15 ku-SAR engu-4.6 W/kg. Lokhu kuvinjelwa kwaguqulwa kancane kuphela phakathi nemizuzu engama-30 yokuchayeka. Ukuthuliswa okuphelele kwama-neurons kufezwe ku-SAR engu-9.2 W/kg. Ukuhlaziywa kokuphendula komthamo kubonise ukuthi i-GSM-1800 MHz yayisebenza kangcono kune-1800 MHz CW ku- ukucindezela umsebenzi wokuqhuma, okuphakamisa ukuthi izimpendulo ze-neuronal zincike ekuguqulweni kwesignali ye-RF.
Esimweni sethu, izimpendulo ezivuswe yi-cortical zaqoqwa ngaphakathi emzimbeni amahora amathathu kuya kwayi-6 ngemuva kokuphela kokuvezwa kwekhanda kwamahora ama-2 kuphela. Esifundweni sangaphambilini, siphenye umphumela we-GSM-1800 MHz ku-SARACx ongu-1.55 W/kg futhi asitholanga mphumela obalulekile ezimpendulweni ze-cortical ezivuswe umsindo kumagundane anempilo. Lapha, umphumela obalulekile kuphela ovuswe kumagundane anempilo ngokuchayeka ku-LTE-1800 ku-0.5 W/kg i-SARACx kwakuwukwanda okuncane esikhathini sempendulo lapho kwethulwa amathoni ahlanzekile. Lo mphumela kunzima ukuwuchaza ngoba awuhambisani nokwanda kwamandla okuphendula, okuphakamisa ukuthi lesi sikhathi eside sempendulo senzeka ngenani elifanayo lamandla esenzo akhishwa ama-neurons e-cortical. Enye incazelo ingaba ukuthi ukuvezwa kwe-LTE kunganciphisa umsebenzi wama-interneurons athile okuvimbela, njengoba kubhaliwe ukuthi ekuvinjelweni kwe-ACx okuyisisekelo kulawula isikhathi sezimpendulo zamaseli e-pyramidal ezibangelwa ukufakwa kwe-thalamic excitatory33,34, 35, 36, 37.
Ngokuphambene nalokho, kumagundane ahlushwa ukuvuvukala kwe-neuroinflammation okubangelwa yi-LPS, ukuvezwa kwe-LTE akuzange kube nomthelela esikhathini sokudubula kwe-neuronal okubangelwa umsindo, kodwa imiphumela ebalulekile yatholakala emandleni ezimpendulo ezibangelwa umsindo. Eqinisweni, uma kuqhathaniswa nezimpendulo ze-neuronal eziqoshwe kumagundane ahlushwe yi-LPS, ama-neurons kumagundane aphathwe yi-LPS ahlushwe yi-LTE abonise ukwehla kwamandla ezimpendulo zawo, umphumela obonwe kokubili lapho eveza amathoni amsulwa kanye nokuzwakala kwemvelo. Ukwehla kwamandla empendulo kumathoni amsulwa kwenzeka ngaphandle kokunciphisa i-bandwidth yokulungisa i-spectral engu-75 dB, futhi njengoba kwenzeka kuwo wonke amandla omsindo, kwaholela ekwandeni kwemingcele ye-acoustic yama-neurons e-cortical kuma-frequency aphansi naphakathi.
Ukwehla kwamandla okuphendula okubangelwayo kubonise ukuthi umphumela wokubonisa i-LTE ku-SARACx ongu-0.5 W/kg ezilwaneni eziphathwe yi-LPS wawufana nowe-GSM-1800 MHz osetshenziswa ku-SARACx ephakeme kathathu (1.55 W/kg) 28. Ngokuphathelene nokubonisa i-GSM, ukuchayeka ekhanda ku-LTE-1800 MHz kunganciphisa ukujabula kwe-neuronal kuma-neurons e-ACx egundane ahlushwa ukuvuvukala kwe-neuroinflammation okubangelwa yi-LPS. Ngokuhambisana nale mbono, siphinde sabona ukuthambekela kokwehla kokuthembeka kokuhlolwa kwezimpendulo ze-neuronal ekukhulumeni (Umfanekiso 4h) kanye nokwehla komsebenzi ozenzakalelayo (Umfanekiso 4i). Kodwa-ke, kube nzima ukunquma ukuthi ukubonisa i-LTE kunciphisa ukujabula kwe-neuronal noma kunciphisa okokufaka kwe-synaptic, ngaleyo ndlela kulawula izimpendulo ze-neuronal ku-ACx.
Okokuqala, lezi zimpendulo ezibuthakathaka zingase zibangelwe ukwehla okungokwemvelo kokujabula kwamaseli e-cortical ngemva kokuchayeka ku-LTE 1800 MHz. Ukusekela lo mbono, i-GSM-1800 MHz kanye ne-1800 MHz-CW zinciphise umsebenzi wokuqhuma lapho zisetshenziswa ngqo ezikhungweni eziyinhloko zama-neurons e-cortical rat anamazinga e-SAR angu-3.2 W/kg kanye no-4.6 W/kg, ngokulandelana, kodwa izinga le-SAR elilinganiselwe lalidingeka ukuze kuncishiswe kakhulu umsebenzi wokuqhuma. Sikhuthaza ukwehla kokujabula okungaphakathi, siphinde sabona amazinga aphansi okudubula okuzenzakalelayo ezilwaneni ezichayeke kunezilwane ezichayeke ezithombeni ezichayeke ezithombeni.
Okwesibili, ukuvezwa kwe-LTE kungathinta nokudluliswa kwe-synaptic kusuka kuma-synapses e-thalamo-cortical noma e-cortical-cortical. Amarekhodi amaningi manje abonisa ukuthi, ku-cortex yokuzwa, ububanzi bokulungiswa kwe-spectral abunqunywa kuphela yizibikezelo ze-thalamic ezihlukile, kodwa ukuthi ukuxhumeka kwe-intracortical kunikeza okokufaka okwengeziwe kwe-spectral kumasayithi e-cortical39,40. Ekuhlolweni kwethu, iqiniso lokuthi i-cortical STRF ibonise ama-bandwidth afanayo ezilwaneni ezivezwe futhi ezivezwe ngokungaqondile lisikisele ngokungaqondile ukuthi imiphumela yokuvezwa kwe-LTE kwakungeyona imiphumela ekuxhumaneni kwe-cortical-cortical. Lokhu futhi kusikisela ukuthi ukuxhumeka okuphezulu kwezinye izifunda ze-cortical ezivezwe ku-SAR kunokulinganiswa ku-ACx (Umfanekiso 2) kungenzeka kungabi yimbangela yezimpendulo ezishintshiwe ezibikwe lapha.
Lapha, ingxenye enkulu yokuqoshwa kwe-cortical okuvezwe yi-LPS ibonise imingcele ephezulu uma kuqhathaniswa nezilwane ezivezwe yi-LPS-sham. Njengoba kuye kwaphakanyiswa ukuthi imingcele ye-cortical acoustic ilawulwa kakhulu ngamandla e-thalamo-cortical synapse39,40, kungasolwa ukuthi ukudluliselwa kwe-thalamo-cortical kuncishiswa kancane ngokuchayeka, kungaba yi-presynaptic (ukukhululwa kwe-glutamate okuncishisiwe) noma izinga le-postsynaptic (inombolo ye-receptor encishisiwe noma i-affinity).
Ngokufanayo nemiphumela ye-GSM-1800 MHz, izimpendulo ze-neuronal ezishintshiwe ezibangelwa yi-LTE zenzeke kumongo wokuvuvukala kwe-neuroinflammation okubangelwa yi-LPS, okubonakala ngezimpendulo ze-microglial. Ubufakazi bamanje busikisela ukuthi i-microglia ithonya kakhulu umsebenzi wamanethiwekhi e-neuronal ebuchosheni obujwayelekile nobe-pathological41,42,43. Amandla abo okulawula ukudluliselwa kwe-neuro akuxhomekile kuphela ekukhiqizweni kwamakhemikhali abawakhiqizayo angase noma angakhawulela ukudluliselwa kwe-neurotransmission, kodwa futhi nasekuhambeni okuphezulu kwezinqubo zabo zamaseli. Ku-cortex yobuchopho, kokubili umsebenzi owandisiwe nowehlisiwe wamanethiwekhi e-neuronal ubangela ukwanda okusheshayo kwesizinda sendawo ye-microglial ngenxa yokukhula kwezinqubo ze-microglial44,45. Ikakhulukazi, ama-protrusion e-microglial aqoqwa eduze kwama-synapses e-thalamocortical asebenzayo futhi angavimbela umsebenzi wama-synapses avusa inkanuko ngokusebenzisa izindlela ezibandakanya ukukhiqizwa kwe-adenosine yendawo ephethwe yi-microglia.
Kumagundane aphathwe yi-LPS athunyelwe ku-GSM-1800 MHz nge-SARACx ku-1.55 W/kg, ukwehla komsebenzi wama-neuron e-ACx kwenzeka ngokukhula kwezinqubo ze-microglial eziphawulwe yizindawo ezibalulekile ezine-Iba1 ku-ACx28 Increase. Lokhu kuqaphela kusikisela ukuthi ukuvuselelwa kwe-microglial okubangelwa ukuvezwa kwe-GSM kungaba negalelo elikhulu ekunciphiseni okubangelwa yi-GSM ezimpendulweni ze-neuronal ezivuselelwa umsindo. Ucwaningo lwethu lwamanje luphikisana nalo mbono kumongo wokuvezwa kwekhanda le-LTE nge-SARACx okukhawulelwe ku-0.5 W/kg, njengoba sithole ukuthi akukho ukwanda kwendawo embozwe yizinqubo ze-microglial. Kodwa-ke, lokhu akususi noma yimuphi umphumela wokubonakaliswa kwe-LTE ku-microglia esebenzayo ye-LPS, okungase kuthinte umsebenzi we-neuronal. Izifundo ezengeziwe ziyadingeka ukuphendula lo mbuzo nokunquma izindlela lapho ukuvuvukala kwe-neuroinflammation okunamandla kushintsha ngazo izimpendulo ze-neuronal ku-LTE signaling.
Ngokwazi kwethu, umphumela wezimpawu ze-LTE ekucutshungulweni kokuzwa awukaze ufundwe ngaphambili. Izifundo zethu zangaphambilini 26,28 kanye nocwaningo lwamanje lubonise ukuthi esimweni sokuvuvukala okukhulu, ukuvezwa kwekhanda lodwa ku-GSM-1800 MHz noma ku-LTE-1800 MHz kuholele ekushintsheni kokusebenza kwezimpendulo ze-neuronal ku-ACx, njengoba kuboniswe ukwanda komkhawulo wokuzwa. Okungenani ngezizathu ezimbili eziyinhloko, umsebenzi we-cochlear akufanele uthintwe ukuvezwa kwethu kwe-LTE. Okokuqala, njengoba kuboniswe ocwaningweni lwe-dosimetry oluboniswe kuMfanekiso 2, amazinga aphezulu e-SAR (aseduze ne-1 W/kg) atholakala ku-dorsomedial cortex (ngaphansi kwe-antenna), futhi ancipha kakhulu njengoba umuntu ehamba kakhulu eceleni nangaseceleni. Ingxenye ye-ventral yekhanda. Kungalinganiselwa ukuthi ingaba ngu-0.1 W/kg ezingeni le-pinna yegundane (ngaphansi komsele wendlebe). Okwesibili, lapho izindlebe ze-guinea pig zivezwa izinyanga ezi-2 ku-GSM 900 MHz (izinsuku ezi-5/ngesonto, ihora eli-1/ngosuku, i-SAR phakathi kuka-1 no-4. W/kg), bekungekho zinguquko ezitholakalayo ngobukhulu bomkhiqizo ophambeneyo i-otoacoustic Thresholds for Emission kanye ne-Auditory Brainstem Responses 47. Ngaphezu kwalokho, ukuchayeka ikhanda okuphindaphindiwe ku-GSM 900 noma i-1800 MHz ku-SAR yendawo engu-2 W/kg akuzange kuthinte ukusebenza kweseli lezinwele zangaphandle ze-cochlear kumagundane anempilo48,49. Le miphumela ihambisana nedatha etholwe kubantu, lapho uphenyo lubonise ukuthi ukuchayeka kwe-EMF imizuzu eyi-10 kuya kwengama-30 kusuka kumaselula e-GSM akunawo umphumela oqhubekayo ekucutshungulweni kokuzwa njengoba kuhlolwe ezingeni le-cochlear50,51,52​​noma izinga le-brainstem53,54.
Esifundweni sethu, izinguquko zokudubula kwe-neuronal ezibangelwa yi-LTE zabonwa ngaphakathi emzimbeni emahoreni amathathu kuya kwayi-6 ngemva kokuphela kokuvezwa. Esifundweni sangaphambilini engxenyeni ye-dorsomedial ye-cortex, imiphumela eminingana ebangelwe yi-GSM-1800 MHz ebonwe emahoreni angama-24 ngemva kokuvezwa yayingasabonakali emahoreni angama-72 ngemva kokuvezwa. Lokhu kunjalo ngokwanda kwezinqubo ze-microglial, ukwehla kwe-IL-1ß gene kanye nokuguqulwa kwangemva kokuhumusha kwama-receptor e-AMPA. Uma sicabanga ukuthi i-cortex yokuzwa inenani eliphansi le-SAR (0.5W/kg) kunesifunda se-dorsomedial (2.94W/kg26), izinguquko emsebenzini we-neuronal ezibikwe lapha zibonakala zidlula isikhathi.
Idatha yethu kufanele icabangele imikhawulo ye-SAR efanelekile kanye nezilinganiso zamanani angempela e-SAR afinyelelwe ku-cortex yobuchopho yabasebenzisi befoni ephathekayo. Izindinganiso zamanje ezisetshenziselwa ukuvikela umphakathi zibeka umkhawulo we-SAR ku-2 W/kg wokuchayeka kwekhanda noma komzimba endaweni ethile kumaza omsakazo ku-100 kHz kanye no-6 GHz RF range.
Ukulinganisa umthamo kwenziwe kusetshenziswa amamodeli ekhanda lomuntu ahlukene ukuze kunqunywe ukumuncwa kwamandla e-RF ezicutshini ezahlukene zekhanda ngesikhathi sokuxhumana kwekhanda noma ngocingo oluphathwayo. Ngaphezu kokuhlukahluka kwamamodeli ekhanda lomuntu, lokhu kulinganisa kugqamisa umehluko omkhulu noma ukungaqiniseki ekulinganiseni amandla amuncwa ubuchopho ngokusekelwe kumapharamitha e-anatomical noma e-histological njengesimo sangaphandle noma sangaphakathi sekhanda, ukujiya, noma okuqukethwe kwamanzi. Izicubu zekhanda ezahlukene ziyahlukahluka kakhulu ngokuya ngobudala, ubulili, noma umuntu ngamunye 56,57,58. Ngaphezu kwalokho, izici zeselula, njengendawo yangaphakathi ye-antenna kanye nendawo yocingo oluphathwayo maqondana nekhanda lomsebenzisi, kuthonya kakhulu izinga nokusatshalaliswa kwamanani e-SAR ku-cortex yobuchopho 59,60. Kodwa-ke, uma sibheka ukusatshalaliswa kwe-SAR okubikiwe ku-cortex yobuchopho yomuntu, okwasungulwa ngamamodeli eselula akhipha amaza omsakazo ebangeni le-1800 MHz 58, 59, 60, kubonakala sengathi amazinga e-SAR afinyelelwe ku-cortex yokuzwa yomuntu asasetshenziswa kahle ingxenye ye-cortex yobuchopho yomuntu. Ucwaningo lwethu (SARACx) 0.5 W/kg). Ngakho-ke, idatha yethu ayiphikisani nemikhawulo yamanje yamanani e-SAR asebenza emphakathini.
Ekuphetheni, ucwaningo lwethu lubonisa ukuthi ukuchayeka okukodwa ekhanda kuphela ku-LTE-1800 MHz kuphazamisa izimpendulo ze-neuronal zama-cortical neurons ezishukunyiswa yizinzwa. Ngokuhambisana nezimpawu zangaphambilini zemiphumela yesignali ye-GSM, imiphumela yethu iphakamisa ukuthi imiphumela yesignali ye-LTE emsebenzini we-neuronal iyahlukahluka ngokwesimo sempilo. Ukuvuvukala kwe-neuroinflammation okunamandla kwenza ama-neurons azwele ku-LTE-1800 MHz, okuholela ekushintsheni kokucubungula kwe-cortical kwezishukunyiswa zokuzwa.
Idatha yaqoqwa ezinsukwini ezingu-55 ubudala kusukela ku-cerebral cortex yamagundane amadala angu-31 e-Wistar atholwe elabhorethri kaJanvier. Amagundane agcinwa endaweni enomswakama (50-55%) kanye nokushisa (22-24 °C) elawulwayo ngomjikelezo wokukhanya/omnyama wamahora angu-12/12 (izibani zivuliwe ngo-7:30am) kanye nokufinyelela mahhala ekudleni namanzi. Zonke izivivinyo zenziwe ngokuhambisana neziqondiso ezisungulwe yi-Council of the European Communities Directive (2010/63/EU Council Directive), ezifana nalezo ezichazwe ku-Society for Neuroscience Guidelines for the Use of Animals in Neuroscience Research. Le protocol yamukelwa yi-Ethics Committee Paris-Sud and Center (CEEA N°59, Project 2014-25, National Protocol 03729.02) kusetshenziswa izinqubo eziqinisekiswe yileli komidi 32-2011 kanye no-34-2012.
Izilwane zahlaliswa emakamelweni ekoloni okungenani isonto elilodwa ngaphambi kokwelashwa kwe-LPS kanye nokuchayeka (noma ukuchayeka mbumbulu) ku-LTE-EMF.
Amagundane angamashumi amabili nambili ajovwe ngaphakathi kwesisu (ip) nge-E. coli LPS (250 µg/kg, serotype 0127:B8, SIGMA) exutshwe ne-sterile endotoxin-free isotonic saline amahora angama-24 ngaphambi kwe-LTE noma ukuvezwa kwe-sham (n ngeqembu ngalinye). = 11).Emagundlwini amaduna aseWistar anezinyanga ezimbili ubudala, lokhu kwelashwa kwe-LPS kukhiqiza impendulo yokuvuvukala kwemizwa ephawulwa ku-cortex yobuchopho yizakhi zofuzo eziningana ezibangela ukuvuvukala (i-tumor necrosis factor-alpha, i-interleukin 1ß, i-CCL2, i-NOX2, i-NOS2) zakhushulwa emahoreni angama-24 ngemuva kokujova kwe-LPS, okuhlanganisa nokwanda okuphindwe ka-4 no-12 emazingeni okubhalwa kwe-enzyme ye-NOX2 kanye ne-interleukin 1ß, ngokulandelana. Kulesi sikhathi samahora angama-24, i-cortical microglia ibonise isimo seseli "esiqinile" esijwayelekile esilindelwe yi-LPS-activation pro-inflammatory yamaseli (Isithombe 1), okungafani nokusebenza kwe-LPS-activation abanye. Ukusebenza kwe-cell pro-inflammatory kuhambelana no-24, 61.
Ukuchayeka ekhanda kuphela ku-LTE EMF kwenziwa kusetshenziswa isethaphu sokuhlola esasisetshenziswa ngaphambilini ukuhlola umphumela we-GSM EMF26. Ukuchayeka kwe-LTE kwenziwa emahoreni angama-24 ngemuva kokujova i-LPS (izilwane eziyi-11) noma akukho ukwelashwa kwe-LPS (izilwane ezi-5). Izilwane zalaliswa kancane nge-ketamine/xylazine (ketamine 80 mg/kg, ip; xylazine 10 mg/kg, ip) ngaphambi kokuchayeka ukuze kuvinjelwe ukunyakaza nokuqinisekisa ukuthi ikhanda lesilwane lise-antenna ye-loop ekhipha isignali ye-LTE Indawo engaphindwa kabusha ngezansi. Ingxenye yamagundane avela ekhejini elifanayo asebenza njengezilawuli (izilwane eziyi-11 ezichayeke nge-sham, kumagundane angama-22 aphathwe nge-LPS ngaphambilini): abekwa ngaphansi kwe-antenna ye-loop futhi amandla esignali ye-LTE abekwe ku-zero. Isisindo sezilwane ezichayeke nge-sham kanye nezichayeke nge-sham zazifana (p = 0.558, i-t-test engabhangqiwe, ns). Zonke izilwane ezilaliswe nge-anesthetised zabekwa ku-heating pad engenansimbi ukuze kugcinwe izinga lokushisa lomzimba wazo licishe libe ngu-37°C kulo lonke ukuhlolwa. Njengoba Ezivivinyweni zangaphambilini, isikhathi sokuchayeka sasibekwe emahoreni ama-2. Ngemva kokuchayeka, beka isilwane kwenye i-heating pad egumbini lokuhlinza. Inqubo efanayo yokuchayeka yasetshenziswa kumagundane ayi-10 aphilile (angaphathwanga nge-LPS), ingxenye yawo eyayichayeke ekhejini elifanayo (p = 0.694).
Uhlelo lokudalulwa lwalufana nezinhlelo ezingu-25, 62 ezichazwe ezifundweni zangaphambilini, lapho ijenereyitha yemvamisa yomsakazo ithathelwe indawo ukuze kukhiqizwe i-LTE esikhundleni samasimu kagesi e-GSM. Ngamafuphi, ijenereyitha ye-RF (SMBV100A, 3.2 GHz, Rohde & Schwarz, Germany) ekhipha insimu kagesi ye-LTE - 1800 MHz ixhunywe ku-amplifier yamandla (ZHL-4W-422+, Mini-Circuits, USA), i-circulator (D3 1719-N, Sodhy, France), i-coupler enezindlela ezimbili (CD D 1824-2, − 30 dB, Sodhy, France) kanye ne-power divider enezindlela ezine (DC D 0922-4N, Sodhy, France), evumela ukuvezwa kwezilwane ezine ngasikhathi sinye. Imitha yamandla (N1921A, Agilent, USA) exhunywe ku-bidirectional coupler ivumele ukulinganiswa okuqhubekayo nokuqapha isigameko futhi yabonisa amandla ngaphakathi kwedivayisi. Ukukhishwa ngakunye kuxhunywe ku-antenna ye-loop (Sama-Sistemi). srl; Roma), okuvumela ukuvezwa okuyingxenye kwekhanda lesilwane. I-antenna ye-loop iqukethe isekethe ephrintiwe enemigqa emibili yensimbi (i-dielectric constant εr = 4.6) eqoshwe ku-substrate ye-epoxy evikelayo. Ngakolunye uhlangothi, idivayisi iqukethe ucingo oluyi-1 mm ububanzi olwenza indandatho ebekwe eduze kwekhanda lesilwane. Njengasezifundweni zangaphambilini26,62, izinga lokumuncwa elithile (i-SAR) lanqunywa ngokwezibalo kusetshenziswa imodeli yegundane lezinombolo kanye nendlela yesizinda sesikhathi somehluko olinganiselwe (i-FDTD)63,64,65. Zanqunywa futhi ngokwezibalo kumodeli yegundane elinganayo kusetshenziswa ama-probe e-Luxtron ukukala ukunyuka kwezinga lokushisa.Kulokhu, i-SAR ku-W/kg ibalwa kusetshenziswa ifomula: I-SAR = C ΔT/Δt, lapho i-C ingumthamo wokushisa ku-J/(kg K), ΔT, ku-°K kanye ne-Δt Ukushintsha kwezinga lokushisa, isikhathi ngemizuzwana.Amanani e-SAR anqunywe ngokwezibalo aqhathaniswa namanani e-SAR okuhlola atholwe kusetshenziswa imodeli elinganayo, ikakhulukazi ezindaweni zobuchopho begundane ezilinganayo.Umehluko phakathi kokulinganisa kwe-SAR yezinombolo kanye Amanani e-SAR atholwe ngokuhlolwa angaphansi kuka-30%.
Isithombe 2a sibonisa ukusatshalaliswa kwe-SAR ebuchosheni begundane kumodeli yegundane, okuhambisana nokusatshalaliswa ngokwesisindo somzimba kanye nosayizi wamagundane asetshenziswe ocwaningweni lwethu. Isilinganiso se-SAR sobuchopho sasingu-0.37 ± 0.23 W/kg (isilinganiso ± SD). Amanani e-SAR aphezulu kakhulu endaweni ye-cortical ngaphansi nje kwe-antenna ye-loop. I-SAR yendawo ku-ACx (SARACx) yayingu-0.50 ± 0.08 W/kg (isilinganiso ± SD) (Isithombe 2b). Njengoba isisindo somzimba samagundane abonakalayo silingana futhi umehluko ekujiyeni kwezicubu zekhanda awubalulekile, i-SAR yangempela ye-ACx noma ezinye izindawo ze-cortical kulindeleke ukuthi ifane kakhulu phakathi kwesilwane esisodwa esibonakalayo nesinye.
Ekupheleni kokuchayeka, izilwane zanezelwa ngemithamo eyengeziwe ye-ketamine (20 mg/kg, ip) kanye ne-xylazine (4 mg/kg, ip) kuze kube yilapho kungekho kunyakaza kwe-reflex okubonwe ngemuva kokucindezela unyawo lwangemuva. I-anesthetic yendawo (i-Xylocain 2%) yajovwa ngaphansi kwesikhumba kanye nemisipha ye-temporalis ngaphezu kogebhezi, futhi izilwane zafakwa ohlelweni lokushisa olungenansimbi. Ngemva kokubeka isilwane ohlakeni lwe-stereotaxic, kwenziwa i-craniotomy phezu kwe-cortex yesobunxele ye-temporal. Njengasesifundweni sethu sangaphambilini66, kusukela ekuhlanganeni kwamathambo e-parietal nawe-temporal, ukuvulwa kwakungu-9 mm ububanzi kanye no-5 mm ukuphakama. I-dura engaphezulu kwe-ACx yasuswa ngokucophelela ngaphansi kokulawulwa kwe-binocular ngaphandle kokulimaza imithambo yegazi. Ekupheleni kwenqubo, kwakhiwe isisekelo nge-acrylic cement yamazinyo ukuze kufakwe ikhanda lesilwane nge-atraumatic ngesikhathi sokuqopha. Beka uhlaka lwe-stereotaxic olusekela isilwane ekamelweni lokunciphisa i-acoustic (IAC, imodeli ye-AC1).
Idatha itholakale ekurekhodweni kwamayunithi amaningi ku-cortex yokuqala yokuzwa kwamagundane angu-20, kufaka phakathi izilwane eziyi-10 ezelashwe nge-LPS. Ukurekhodwa kwangaphandle kwamangqamuzana kutholakale kuhlu lwama-electrode angu-16 e-tungsten (TDT, ø: 33 µm, < 1 MΩ) aqukethe imigqa emibili yama-electrode angu-8 ahlukaniswe ngo-1000 µm (350 µm phakathi kwama-electrode emgqeni ofanayo). Ucingo lwesiliva (ø: 300 µm) lokufaka isisekelo lufakwe phakathi kwethambo lesikhashana kanye ne-dura engezansi. Indawo elinganisiwe ye-ACx eyinhloko ingu-4-7 mm ngemuva kwe-bregma kanye no-3 mm ventral kuya ku-supratemporal suture. Isignali eluhlaza yandiswa izikhathi eziyi-10,000 (TDT Medusa) bese icutshungulwa uhlelo lokuthola idatha oluneziteshi eziningi (RX5, TDT). Izimpawu eziqoqwe ku-electrode ngayinye zahlungwa (610–10,000 Hz) ukuze kukhishwe umsebenzi wamayunithi amaningi. (MUA). Amazinga e-trigger abekwe ngokucophelela ku-electrode ngayinye (ngababhali abasebenzisana nabo abangaboni izimo eziveziwe noma ezivezwe ngamanga) ukuze kukhethwe amandla amakhulu esenzo esignalini. Ukuhlolwa kwe-inthanethi kanye nokungaxhunywanga kwama-waveform kubonise ukuthi i-MUA eqoqwe lapha yayiqukethe amandla esenzo akhiqizwa ama-neurons angu-3 kuya kwangu-6 eduze kwama-electrode. Ekuqaleni kokuhlolwa ngakunye, simise indawo ye-electrode array ukuze imigqa emibili yama-electrode ayisishiyagalombili ikwazi ukusampula ama-neurons, kusukela ekuphenduleni okuphansi kuya kokuphezulu lapho kwenziwa endaweni yokuma.
Izisusa ze-acoustic zakhiqizwa ku-Matlab, zadluliselwa ohlelweni lokulethwa komsindo olusekelwe ku-RP2.1 (TDT) zathunyelwa ku-loudspeaker ye-Fostex (FE87E). I-loudspeaker yabekwa ngamasentimitha ama-2 ukusuka endlebeni yesokudla yegundane, lapho i-loudspeaker yakhipha khona ububanzi bemvamisa eyisicaba (± 3 dB) phakathi kuka-140 Hz no-36 kHz. Ukulinganiswa kwe-loudspeaker kwenziwa kusetshenziswa umsindo kanye namathoni amsulwa aqoshwe nge-microphone ye-Bruel ne-Kjaer 4133 ehlanganiswe ne-preamplifier B&K 2169 kanye ne-digital recorder Marantz PMD671. I-Spectral Time Receptive Field (STRF) yanqunywa kusetshenziswa amaza e-gamma-tone angu-97, ahlanganisa ama-octave angu-8 (0.14–36 kHz), anikezwe ngokulandelana okungahleliwe ku-75 dB SPL ku-4.15 Hz. I-Frequency Response Area (FRA) yanqunywa kusetshenziswa isethi efanayo yamathoni futhi yanikezwa ngokulandelana okungahleliwe ku-2 Hz kusuka ku-75 kuya ku-5 dB SPL. Imvamisa ngayinye ivezwa izikhathi eziyisishiyagalombili ngamandla ngakunye.
Izimpendulo ezishukumisweni zemvelo nazo zahlolwa. Ezifundweni zangaphambilini, sibonile ukuthi ukuzwakala kwamagundane akuvamile ukuveza izimpendulo ezinamandla ku-ACx, kungakhathaliseki ukuthi imvamisa ye-neuronal optimal (BF), kuyilapho i-xenograft-specific (isb., ukuzwakala kwezinyoni eziculayo noma i-guinea pig) ngokuvamile kuyimephu yethoni yonke. Ngakho-ke, sihlole izimpendulo ze-cortical ekuzweni kwemisindo kuma-guinea pig (impempe esetshenziswe ku-36 yayixhunywe ku-1 s yezishukumi, eyethulwe izikhathi ezingu-25).

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