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Imfuno ekhulayo yonxibelelwano lwefowuni ephathwayo ikhokelele ekuveleni okuqhubekayo kwezobuchwepheshe ezingenazingcingo (G), ezinokuba nefuthe elahlukileyo kwiinkqubo zebhayoloji. Ukuvavanya oku, siveze iimpuku ukuba zichaphazeleke ngentloko enye kwi-4G long-term evolution (LTE)-1800 MHz electromagnetic field (EMF) kangangeeyure ezi-2. Emva koko sivavanye isiphumo se-lipopolysaccharide-induced acute neuroinflammation kwi-microglia spatial coverage kunye nomsebenzi we-electrophysiological neuronal kwi-primary auditory cortex (ACx). I-SAR ephakathi kwi-ACx yi-0.5 W/kg. Iirekhodi ze-Multi-unit zibonisa ukuba i-LTE-EMF ibangela ukwehla kobunzima bempendulo kwiithoni ezicocekileyo kunye nesandi sendalo, ngelixa ukwanda komlinganiselo we-acoustic kwiifrequencies eziphantsi neziphakathi. I-Iba1 immunohistochemistry ayibonisanga lutshintsho kwindawo egutyungelwe yimizimba ye-microglial kunye neenkqubo. Kwiimpuku eziphilileyo, ukubonakaliswa okufanayo kwe-LTE akuzange kubangele utshintsho kubunzulu bempendulo kunye nemida ye-acoustic. Idatha yethu ibonisa ukuba ukuvuvukala kwe-acute neuroinflammation kwenza ii-neurons zivakale kwi-LTE-EMF, nto leyo ekhokelela ekuguqulweni kwenkqubo ye-acoustic stimuli kwi-ACx.
Imeko-bume ye-electromagnetic yoluntu itshintshe kakhulu kwiminyaka engamashumi amathathu edlulileyo ngenxa yokwanda okuqhubekayo konxibelelwano olungenazingcingo. Okwangoku, ngaphezulu kwesibini kwisithathu sabantu bathathwa njengabasebenzisi beefowuni eziphathwayo (MP). Ukusasazeka okukhulu kwale teknoloji kubangele inkxalabo kunye nengxoxo malunga nemiphumo enokuba yingozi ye-pulsed electromagnetic fields (EMFs) kuluhlu lwe-radio frequency (RF), ezikhutshwa yi-MPs okanye izikhululo zesiseko kwaye zifake ikhowudi yonxibelelwano. Le ngxaki yempilo yoluntu ikhuthaze izifundo ezininzi zovavanyo ezizinikele ekuphandeni iziphumo zokufunxwa kwe-radiofrequency kwizicubu zebhayoloji1. Ezinye zezi zifundo zikhangele utshintsho kwimisebenzi yenethiwekhi ye-neuronal kunye neenkqubo zokuqonda, ngenxa yokuba ubuchopho bukufutshane nemithombo ye-RF phantsi kokusetyenziswa ngokubanzi kwe-MP. Izifundo ezininzi ezibikiweyo zijongana nemiphumo ye-pulse modulated signals ezisetyenziswa kwinkqubo yehlabathi yesizukulwana sesibini (2G) yonxibelelwano oluphathwayo (GSM) okanye i-wideband code division multiple access (WCDMA)/third generation universal mobile telecommunications systems (WCDMA/3G UMTS)2,3,4,5.Kuncinci okwaziwayo malunga nemiphumo ye-radio frequency signals ezisetyenziswa kwiinkonzo zeselula zesizukulwana sesine (4G), ezixhomekeke kwi Iteknoloji ye-Intanethi yedijithali yonke ebizwa ngokuba yiteknoloji yeLong Term Evolution (LTE). Iqaliswe ngo-2011, inkonzo yefowuni ye-LTE kulindeleke ukuba ifikelele kubabhalisi be-LTE behlabathi abayi-6.6 yezigidigidi ngoJanuwari 2022 (GSMA: //gsacom.com). Xa ithelekiswa neenkqubo ze-GSM (2G) kunye ne-WCDMA (3G) ezisekelwe kwiinkqubo ze-modulation ze-single-carrier modulation, i-LTE isebenzisa i-Orthogonal Frequency Division Multiplexing (OFDM) njengefomathi yesignali esisiseko.6 Kwihlabathi liphela, iinkonzo zeselula ze-LTE zisebenzisa uluhlu lweebhendi ezahlukeneyo zefrikhwensi phakathi kwe-450 kunye ne-3700 MHz, kubandakanya neebhendi ze-900 kunye ne-1800 MHz ezisetyenziswa kwi-GSM.
Amandla okuvezwa yi-RF ekuchaphazeleni iinkqubo zebhayoloji axhomekeke kakhulu kwizinga elithile lokufunxwa (i-SAR) elibonakaliswa kwi-W/kg, elilinganisa amandla afunxwa kwizicubu zebhayoloji. Iziphumo zokuvezwa kwentloko ngokukhawuleza kwimizuzu engama-30 kwizibonakaliso ze-2.573 GHz LTE kumsebenzi wenethiwekhi yehlabathi ye-neuronal zihlolwe kutshanje kubantu abazinikeleyo abasempilweni. Ngokusebenzisa i-fMRI yesimo sokuphumla, kwabonwa ukuba ukuvezwa kwe-LTE kunokubangela ukuguquguquka okucothayo rhoqo kunye notshintsho kunxibelelwano lwangaphakathi okanye phakathi kwengingqi, ngelixa amanqanaba e-SAR aphezulu kwisithuba esingaphezulu kwe-10 g yezicubu aqikelelwa ukuba ahluka phakathi kwe-0.42 kunye ne-1.52 W/ kg, ngokwezihloko 7, 8, 9. Uhlalutyo lwe-EEG phantsi kweemeko ezifanayo zokuvezwa (ubude bemizuzu engama-30, inqanaba le-SAR eliqikelelweyo le-1.34 W/kg kusetyenziswa imodeli yentloko yomntu emeleyo) lubonise amandla anciphileyo e-spectral kunye nokuhambelana kwe-hemispheric kwiibhendi ze-alpha kunye ne-beta. Nangona kunjalo, ezinye izifundo ezimbini ezisekelwe kuhlalutyo lwe-EEG zifumanise ukuba imizuzu engama-20 okanye engama-30 yokuvezwa kwentloko ye-LTE, kunye namanqanaba aphezulu e-SAR asekuhlaleni abekwe malunga ne-2 W/kg, nokuba ayinayo isiphumo esibonakalayo11 okanye esibangele amandla e-spectral kwi-alpha band anciphile, ngelixa ukuqonda kungatshintshanga kumsebenzi ovavanyiweyo ngovavanyo lweStroop 12. Umahluko omkhulu ufunyenwe nakwiziphumo ze-EEG okanye izifundo zengqondo ezijonga ngokukodwa iziphumo zokuvezwa kwe-GSM okanye i-UMTS EMF. Kucingelwa ukuba zivela kwiinguqu kuyilo lwendlela kunye neeparameter zovavanyo, kubandakanya uhlobo lwesignali kunye nokuguquguquka, ubungakanani bokuvezwa kunye nobude bexesha, okanye ukungafani kwabantu abafundiswayo malunga nobudala, i-anatomy, okanye isini.
Okwangoku, zimbalwa izifundo zezilwanyana ezisetyenzisiweyo ukufumanisa indlela ukuvezwa kwi-LTE signaling echaphazela ngayo ukusebenza kwengqondo. Kutshanje kuye kwaxelwa ukuba ukuvezwa kwinkqubo yemfuza kwiimpuku ezisakhulayo ukusuka kwinqanaba lokugqibela lokukhula ukuya ekuncanciseni (30 min/day, 5 days/week, kunye ne-SAR yomzimba wonke eyi-0.5 okanye i-1 W/kg) kubangele utshintsho kwindlela yokuziphatha kwemisipha kunye nokutya xa umntu emdala. 14. Ukuvezwa okuphindaphindiweyo kwenkqubo yemfuza (2 ha ngosuku kangangeeveki ezi-6) kwiimpuku ezindala kufunyenwe kubangela uxinzelelo lwe-oxidative kwaye kunciphisa ubukhulu bezinto ezibonakalayo ezifunyenwe kwi-optic nerve, kunye ne-SAR ephezulu eqikelelwa ukuba iphantsi njenge-10 mW/kg15.
Ukongeza kuhlalutyo kwiisikali ezininzi, kuquka amanqanaba eeseli kunye neemolekyuli, iimodeli zeempuku zingasetyenziselwa ukufunda iziphumo zokuvezwa yiRF ngexesha lesifo, njengoko bekugxilwe ngaphambili kwi-GSM okanye kwi-WCDMA/3G UMTS EMF kwimeko yokudumba kwe-neuroinflammation ebukhali. Izifundo zibonise iziphumo zokuxhuzula, izifo ze-neurodegenerative okanye ii-gliomas 16,17,18,19,20.
Iimpuku ezifakwe kwi-Lipopolysaccharide (LPS) ziyimodeli yakudala yokuphendula ngokukhawuleza kwe-neuroinflammatory enxulunyaniswa nezifo ezosulelayo ezibangelwa ziintsholongwane okanye iibhaktheriya ezichaphazela uninzi lwabantu minyaka le. Le meko yokudumba ikhokelela kwisifo esiguqukayo kunye ne-depression behavioral syndrome ebonakaliswa ngumkhuhlane, ukuphelelwa ngumdla wokutya, kunye nokunciphisa ukusebenzisana kwezentlalo. Ii-phagocytes ze-CNS ezihlala apha ezifana ne-microglia ziiseli eziphambili zempembelelo yale mpendulo yokudumba kwe-neuro. Unyango lweempuku nge-LPS lubangela ukusebenza kwe-microglia ebonakaliswa ngokutshintsha imo yazo kunye neenkqubo zeseli kunye notshintsho olukhulu kwiprofayili ye-transcriptome, kubandakanya ukwandiswa kweejini ezifaka ii-cytokines okanye ii-enzymes ezibangela ukudumba, ezichaphazela iinethiwekhi ze-neuronal Imisebenzi 22, 23, 24.
Sifunda iziphumo zokuvezwa kwentloko enye yeeyure ezi-2 kwi-GSM-1800 MHz EMF kwiigundane eziphathwe yi-LPS, sifumanise ukuba i-GSM signaling ibangela iimpendulo zeseli kwi-cerebral cortex, nto leyo echaphazela ukubonakaliswa kwezakhi zofuzo, i-glutamate receptor phosphorylation, i-neuronal Meta-evoked firing kunye ne-morphology ye-microglia kwi-cerebral cortex. Ezi ziphumo azizange zifunyanwe kwiigundane eziphilileyo ezifumene ukuvezwa okufanayo kwe-GSM, nto leyo ebonisa ukuba imeko ye-neuroinflammatory ebangelwa yi-LPS ivuselela iiseli ze-CNS kwi-GSM signaling. Sigxile kwi-auditory cortex (ACx) yeegundane eziphathwe yi-LPS, apho i-SAR yendawo iphakathi kwe-1.55 W/kg, siqaphele ukuba ukuvezwa kwe-GSM kubangele ukwanda kobude okanye ukuhlanganiswa kweenkqubo ze-microglial kunye nokwehla kwempendulo ze-neuronal ezibangelwa ziitoni ezicocekileyo kunye ne-.Natural Stimulation 28.
Kolu phononongo lwangoku, besijonge ukuphonononga ukuba ukuvezwa kwentloko kuphela kwimiqondiso ye-LTE-1800 MHz kunokutshintsha na imo ye-microglial kunye nomsebenzi we-neuronal kwi-ACx, kunciphisa amandla okuvezwa ngesibini kwisithathu. Sibonisa apha ukuba ukubonakaliswa kwe-LTE akuzange kube nafuthe kwiinkqubo ze-microglial kodwa kusabangela ukwehla okukhulu komsebenzi we-cortical ovuswa yisandi kwi-ACx yeempuku eziphathwe yi-LPS ezinexabiso le-SAR le-0.5 W/kg.
Ngenxa yobungqina bangaphambili bokuba ukuchatshazelwa yi-GSM-1800 MHz kutshintshe indlela esebenza ngayo i-microglial phantsi kweemeko ezibangela ukudumba, siphande esi siphumo emva kokuchatshazelwa yi-LTE signaling.
Iimpuku ezindala zifakwe i-LPS kwiiyure ezingama-24 ngaphambi kokuba zibonakale nge-sham entloko kuphela okanye zibonakale kwi-LTE-1800 MHz. Emva kokuba zibonakaliswe, iimpendulo ze-neuroinflammatory ezibangelwa yi-LPS zamiselwa kwi-cortex ye-cerebral, njengoko kuboniswe kukunyuka kwezakhi zofuzo ezibangela ukuvuvukala kunye notshintsho kwimo ye-cortical microglia (Umfanekiso 1). Amandla abonakaliswe yintloko ye-LTE amiselwe ukufumana inqanaba eliphakathi le-SAR le-0.5 W/kg kwi-ACx (Umfanekiso 2). Ukufumanisa ukuba i-microglia esebenzayo ye-LPS iyasabela kwi-LTE EMF, sihlalutye amacandelo e-cortical anombala we-anti-Iba1 abhala ngokukhetha la maseli. Njengoko kubonisiwe kuMfanekiso 3a, kumacandelo e-ACx alungisiweyo kwiiyure ezi-3 ukuya kwezi-4 emva kokuba zibonakaliswe nge-sham okanye i-LTE, i-microglia ibukeka ifana kakhulu, ibonisa imo yeseli "efana ne-dense" evezwe lunyango lwe-LPS olubangela ukuvuvukala (Umfanekiso 1). Ngokuhambelana nokungabikho kweempendulo zemo, uhlalutyo lomfanekiso wobungakanani alubonisanga mahluko abalulekileyo kwindawo iyonke (uvavanyo lwe-t olungabhangqwanga, p = 0.308) okanye indawo (p = 0.196) kunye noxinano (p = 0.061) lwe-Iba1 immunoreactivity xa kuthelekiswa ukuvezwa kwimizimba yeeseli ze-Iba 1 ezinemibala kwiigundane ze-LTE ngokuchasene nezilwanyana ezivezwe buxoki (Umzobo 3b-d).
Iziphumo ze-LPS ip injection kwi-cortical microglia morphology. Umbono omele i-microglia kwicandelo le-coronal le-cerebral cortex (ummandla we-dorsomedial) kwiiyure ezingama-24 emva kokufakwa kwe-LPS okanye isithuthi ngaphakathi kwe-peritoneal (ulawulo). Iiseli zadakazwa nge-anti-Iba1 antibody njengoko kuchaziwe ngaphambili. Unyango lwe-LPS olubangela ukudumba lubangele utshintsho kwi-microglia morphology, kubandakanya ukuqina kwe-proximal kunye nokwanda kwamasebe amafutshane esibini eenkqubo zeseli, okubangela ukubonakala "okufana nobunzima". I-Scale bar: 20 µm.
Uhlalutyo lwe-Dosimetric lwe-specific absorption rate (SAR) kwingqondo yegundane ngexesha lokuvezwa kwi-1800 MHz LTE. Imodeli eyahlukileyo echazwe ngaphambili ye-phantom rat kunye ne-loop antenna62 isetyenzisiwe ukuvavanya i-SAR yendawo engqondweni, ngegridi ye-cubic ye-0.5 mm3.(a) Umbono wehlabathi jikelele wemodeli yegundane kwindawo yokuvezwa ene-antenna ye-loop ngaphezulu kwentloko kunye ne-metallic thermal pad (etyheli) ngaphantsi komzimba.(b) Ukusasazwa kwamaxabiso e-SAR kwingqondo yabantu abadala kwisisombululo sendawo se-0.5 mm3. Indawo eyahlulwe ngumda omnyama kwicandelo le-sagittal ihambelana ne-cortex yokuqala yokuva apho umsebenzi we-microglial kunye ne-neuronal uhlalutywa khona. Isikali sekhowudi yombala samaxabiso e-SAR sisebenza kuzo zonke ii-simulations zamanani eziboniswe kumfanekiso.
I-microglia efakwe kwi-LPS kwi-cortex ye-auditory yegundane emva kokuvezwa yi-LTE okanye yi-Sham.(a) Umbono omeleyo we-microglia efakwe i-anti-Iba1 antibody kwiindawo ze-coronal ze-LPS-perfused rat auditory cortex kwiiyure ezi-3 ukuya kwezi-4 emva kokuvezwa yi-Sham okanye yi-LTE (ukuvezwa). Ibha yesikali: 20 µm.(bd) Uvavanyo lwe-morphometric ye-microglia kwiiyure ezi-3 ukuya kwezi-4 emva kokuvezwa yi-sham (amachaphaza avulekileyo) okanye ukuvezwa yi-LTE (amachaphaza amnyama abonakalisiweyo).(b, c) Ukugubungela kwendawo (b) kophawu lwe-microglia i-Iba1 kunye neendawo zemizimba yeeseli ze-Iba1-positive (c). Idatha imele indawo yokudaya i-anti-Iba1 eqheleke ngokwe-mean evela kwizilwanyana ezivezwe yi-Sham.(d) Inani lemizimba yeeseli ze-microglial ezivezwe yi-anti-Iba1. Umahluko phakathi kwezilwanyana ze-Sham (n = 5) kunye ne-LTE (n = 6) awuzange ubaluleke (p > 0.05, uvavanyo lwe-t olungabhangqwanga). Phezulu nasezantsi kwebhokisi, imigca ephezulu nesezantsi imele Ipesenti ezingama-25 ukuya kuma-75 kunye nepesenti ezingama-5 ukuya kuma-95, ngokulandelelana. Ixabiso eliphakathi liphawulwe ngombala obomvu ebhokisini.
Itheyibhile 1 ishwankathela amanani ezilwanyana kunye neerekhodi ze-multi-unit ezifunyenwe kwi-primary auditory cortex yamaqela amane eempuku (Sham, Exposed, Sham-LPS, Exposed-LPS). Kwiziphumo ezingezantsi, siquka zonke iirekhodi ezibonisa intsimi yokwamkela i-spectral temporal (STRF), oko kukuthi, iimpendulo ezivuselelwe yithoni ubuncinane iinguqu ezi-6 ezisemgangathweni eziphezulu kunezinga lokudubula okuzenzekelayo (jonga iTheyibhile 1). Sisebenzisa le khrayitheriya, sikhethe iirekhodi ezingama-266 zeqela leSham, iirekhodi ezingama-273 zeqela leExposed, iirekhodi ezingama-299 zeqela leSham-LPS, kunye neerekhodi ezingama-295 zeqela leExposed-LPS.
Kwimihlathi elandelayo, siza kuqala sichaze iiparameters ezithathwe kwi-spectral-temporal receptive field (oko kukuthi, impendulo kwiithoni ezicocekileyo) kunye nempendulo kwi-xenogeneic specific vocalizations. Siza kuchaza ubungakanani bendawo yempendulo ye-frequency efunyenwe kwiqela ngalinye. Sicinga ngobukho "bedatha edibeneyo"30 kuyilo lwethu lovavanyo, lonke uhlalutyo lwezibalo lwenziwe ngokusekelwe kwinani lezikhundla kwi-electrode array (umqolo wokugqibela kwiTheyibhile 1), kodwa zonke iziphumo ezichazwe ngezantsi nazo zisekelwe kwinani lezikhundla kwiqela ngalinye. Inani lilonke leerekhodi ze-multiunit eziqokelelweyo (umqolo wesithathu kwiTheyibhile 1).
Umfanekiso 4a ubonisa usasazo oluchanekileyo lwefrikhwensi (BF, olubangela impendulo ephezulu kwi-75 dB SPL) yee-cortical neurons ezifunyenwe kwi-LPS-treated Sham kunye nezilwanyana ezivezwe. Uluhlu lwefrikhwensi ye-BF kumaqela omabini lwandisiwe ukusuka kwi-1 kHz ukuya kwi-36 kHz. Uhlalutyo lwezibalo lubonise ukuba olu sasazo lwalufana (chi-square, p = 0.278), nto leyo ebonisa ukuba uthelekiso phakathi kwamaqela amabini lunokwenziwa ngaphandle kokukhetha iisampulu.
Iziphumo zokuvezwa kwe-LTE kwiiparameter ezilinganisiweyo zeempendulo ze-cortical kwizilwanyana eziphathwe nge-LPS.(a) Ukusasazwa kwe-BF kwii-neurons ze-cortical zezilwanyana eziphathwe nge-LPS ezivezwe kwi-LTE (emnyama) kunye ne-sham-exposed kwi-LTE (emhlophe). Akukho mahluko phakathi kokusasazwa okubini.(bf) Isiphumo sokuvezwa kwe-LTE kwiiparameter ezilinganisa intsimi yokwamkela i-spectral temporal (STRF). Amandla okuphendula ancitshiswe kakhulu (*p < 0.05, uvavanyo lwe-t olungabhangqwanga) kuzo zombini i-STRF (amandla okuphendula apheleleyo) kunye nee-frequency ezifanelekileyo (b,c). Ubude bempendulo, i-bandwidth yokuphendula, kunye ne-bandwidth constant (df). Zombini amandla kunye nokuthembeka kwexesha leempendulo kwizwi kuncitshisiwe (g, h). Umsebenzi ozenzekelayo awuncitshiswanga kakhulu (i).(*p < 0.05, uvavanyo lwe-t olungabhangqwanga).(j,k) Iziphumo zokuvezwa kwe-LTE kwii-thresholds ze-cortical. I-thresholds eziphakathi zaziphezulu kakhulu kwiigundane ezivezwe yi-LTE xa kuthelekiswa neegundane ezivezwe yi-sham. Esi siphumo sibonakala ngakumbi kwii-frequency eziphantsi neziphakathi.
Imifanekiso 4b-f ibonisa ukusasazwa kweeparameters ezithathwe kwi-STRF kwezi zilwanyana (indlela eboniswe yimigca ebomvu). Iziphumo zokuvezwa kwe-LTE kwizilwanyana eziphathwe yi-LPS zibonakala zibonisa ukuncipha kokuvuseleleka kwe-neuronal. Okokuqala, amandla okuphendula ngokubanzi kunye neempendulo beziphantsi kakhulu kwi-BF xa kuthelekiswa nezilwanyana ze-Sham-LPS (Umzobo 4b,c unpaired t-test, p = 0.0017; kunye no-p = 0.0445). Ngokufanayo, iimpendulo kwizandi zonxibelelwano zehlile kumandla okuphendula kunye nokuthembeka phakathi kwezilingo (Umzobo 4g,h; unpaired t-test, p = 0.043). Umsebenzi ozenzekelayo wehlisiwe, kodwa esi siphumo sasingabalulekanga (Umzobo 4i; p = 0.0745). Ubude bempendulo, i-bandwidth yokulungisa, kunye ne-response latency azichaphazelekanga kukuvezwa kwe-LTE kwizilwanyana eziphathwe yi-LPS (Umzobo 4d-f), ebonisa ukuba ukukhetha rhoqo kunye nokuchaneka kweempendulo zokuqala azichaphazelekanga kukuvezwa kwe-LTE kwizilwanyana eziphathwe yi-LPS.
Emva koko sivavanye ukuba ingaba imida ye-cortical yethoni emsulwa itshintshiwe yi-LTE exposure. Ukusuka kwindawo yempendulo ye-frequency (FRA) efunyenwe kwirekhodi nganye, simisele imida ye-auditory ye-frequency nganye kwaye sayilinganisa le mida yamaqela omabini ezilwanyana. Umfanekiso 4j ubonisa imida ye-average (± sem) ukusuka kwi-1.1 ukuya kwi-36 kHz kwiigundane eziphathwe yi-LPS. Ukuthelekisa imida ye-auditory yamaqela e-Sham kunye ne-Exposed kubonise ukwanda okukhulu kwemida kwizilwanyana eziveziweyo xa kuthelekiswa nezilwanyana ze-Sham (Umzobo 4j), isiphumo esasibonakala ngakumbi kwimida ye-low and mid. Ngokuchanekileyo, kwimida ye-low (< 2.25 kHz), umlinganiselo wee-neurons ze-A1 ezinomda ophezulu unyukile, ngelixa umlinganiselo wee-neurons eziphantsi neziphakathi zomda wehla (chi-square = 43.85; p < 0.0001; Umfanekiso 4k, ekhohlo Umfanekiso). Isiphumo esifanayo sibonwe kwi-mid-frequency (2.25 < Freq(kHz) < 11): inani eliphezulu leerekhodi ze-cortical ezine-intermediate thresholds kunye nenani elincinci lee-neurons ezine-low thresholds xa kuthelekiswa neqela elingatyhilekanga (Chi - Square = 71.17; p < 0.001; Umfanekiso 4k, iphaneli ephakathi). Bekukho umahluko omkhulu kwi-threshold yee-neurons ezine-frequency ephezulu (≥ 11 kHz, p = 0.0059); inani lee-neurons ezine-threshold thresholds linciphile kwaye inani le-mid-high threshold linyukile (chi-square = 10.853; p = 0.04 Umfanekiso 4k, iphaneli yasekunene).
Umfanekiso 5a ubonisa usasazo oluchanekileyo lwefrikhwensi (BF, olubangela impendulo ephezulu kwi-75 dB SPL) yee-cortical neurons ezifunyenwe kwizilwanyana eziphilileyo kwiqela leSham kunye neliveziweyo. Uhlalutyo lwezibalo lubonise ukuba usasazo olubini lwalufana (chi-square, p = 0.157), nto leyo ebonisa ukuba uthelekiso phakathi kwamaqela amabini lunokwenziwa ngaphandle kokukhetha iisampulu.
Iziphumo zokuvezwa kwe-LTE kwiiparameter ezilinganisiweyo zeempendulo ze-cortical kwizilwanyana eziphilileyo.(a) Ukusasazwa kwe-BF kwii-neurons ze-cortical zezilwanyana eziphilileyo ezivezwe kwi-LTE (uluhlaza okwesibhakabhaka obumnyama) kunye ne-sham-exposed kwi-LTE (uluhlaza okwesibhakabhaka okhanyayo). Akukho mahluko phakathi kokusasazwa okubini.(bf) Isiphumo sokuvezwa kwe-LTE kwiiparameter ezilinganisa intsimi ye-spectral temporal receptive (STRF). Akukho tshintsho lubalulekileyo kubunzulu bempendulo kuyo yonke i-STRF kunye ne-optimal frequencies (b, c). Kukho ukunyuka okuncinci kwixesha lempendulo (d), kodwa akukho tshintsho kwi-bandwidth yempendulo kunye ne-bandwidth (e, f). Amandla okanye ukuthembeka kwexesha leempendulo kwizwi azitshintshanga (g, h). Akukho tshintsho lubalulekileyo kumsebenzi ozenzekelayo (i).(*p < 0.05 unpaired t-test).(j,k) Iziphumo zokuvezwa kwe-LTE kwiithresholds ze-cortical.Ngokomyinge, iithresholds azitshintshanga kakhulu kwiigundane ezivezwe yi-LTE xa kuthelekiswa neegundane ezivezwe yi-Sham, kodwa iithresholds eziphezulu zaziphantsi kancinci kwizilwanyana ezivezwe.
Imifanekiso 5b-f ibonisa iibhokisi ezibonisa usasazo kunye ne-mean (umgca obomvu) weeparameter ezithathwe kwiiseti ezimbini ze-STRF. Kwizilwanyana eziphilileyo, ukuvezwa kwe-LTE ngokwako bekunempembelelo encinci kwixabiso eliphakathi leeparameter ze-STRF. Xa kuthelekiswa neqela le-Sham (iibhokisi ezikhanyayo vs eziluhlaza okwesibhakabhaka ezimnyama kwiqela eliveziweyo), ukuvezwa kwe-LTE akuzange kutshintshe ubungakanani bempendulo iyonke okanye impendulo ye-BF (Umzobo 5b, c; uvavanyo lwe-t olungabhangqwanga, p = 0.2176, kunye no-p = 0.8696 ngokwahlukeneyo). Akuzange kubekho mpembelelo kwi-bandwidth ye-spectral kunye ne-latency (p = 0.6764 kunye no-p = 0.7129, ngokwahlukeneyo), kodwa bekukho ukwanda okukhulu kwexesha lokuphendula (p = 0.047). Akuzange kubekho mpembelelo kumandla eempendulo zezwi (Umzobo 5g, p = 0.4375), ukuthembeka phakathi kwezilingo kwezi mpendulo (Umzobo 5h, p = 0.3412), kunye nomsebenzi ozenzekelayo (Umzobo 5).5i; p = 0.3256).
Umfanekiso 5j ubonisa imilinganiselo ephakathi (± sem) ukusuka kwi-1.1 ukuya kwi-36 kHz kwiimpuku eziphilileyo. Ayizange ibonise umahluko omkhulu phakathi kwe-sham kunye neempuku eziveziweyo, ngaphandle komda ophantsi kancinci kwizilwanyana eziveziweyo kwiifrequencies eziphezulu (11–36 kHz) (uvavanyo lwe-t olungabhangqwanga, p = 0.0083). Esi siphumo sibonisa inyani yokuba kwizilwanyana eziveziweyo, kolu luhlu lweefriquence (chi-square = 18.312, p = 0.001; Umzobo 5k), bekukho ii-neurons ezingaphezulu kancinci ezinemilinganiselo ephantsi nephakathi (ngelixa imida ephezulu) ii-neurons ezimbalwa).
Ukuqukumbela, xa izilwanyana eziphilileyo zazichatshazelwa yi-LTE, akukho mpembelelo kumandla okuphendula kwiithoni ezicocekileyo nezandi ezintsonkothileyo ezifana nokuvakala kwelizwi. Ngaphezu koko, kwizilwanyana eziphilileyo, imida yokuva ye-cortical yayifana phakathi kwezilwanyana ezichatshazelweyo nezingeyonyani, ngelixa kwizilwanyana eziphathwe yi-LPS, ukuvezwa kwe-LTE kwabangela ukwanda okukhulu kwemida ye-cortical, ngakumbi kuluhlu oluphantsi noluphakathi.
Uphononongo lwethu lubonise ukuba kwiigundane ezindala ezingamadoda ezifumana ukudumba okukhulu kwe-neuroinflammation, ukuvezwa kwi-LTE-1800 MHz ene-SARACx yendawo ye-0.5 W/kg (jonga iiNdlela) kubangele ukwehla okukhulu kubunzulu beempendulo ezivuselelwa sisandi kwiirekhodi zokuqala zonxibelelwano. Olu tshintsho kumsebenzi we-neuronal lwenzeka ngaphandle kotshintsho olubonakalayo kubungakanani bendawo yendawo egutyungelwe ziinkqubo ze-microglial. Esi siphumo se-LTE kubunzulu beempendulo ezivuselelwe yi-cortical asibonwanga kwiigundane eziphilileyo. Ukuqwalasela ukufana kokusasazwa kwefrikhwensi efanelekileyo phakathi kweeyunithi zokurekhoda kwizilwanyana ezivezwe yi-LTE nezivezwe yi-sham, umahluko kwi-reactivity ye-neuronal unokubangelwa yimiphumo yebhayoloji yezibonakaliso ze-LTE endaweni yokukhetha iisampulu (Umzobo 4a). Ngaphezu koko, ukungabikho kotshintsho kwi-response latency kunye ne-spectral tuning bandwidth kwiimpuku ezivezwe yi-LTE kubonisa ukuba, mhlawumbi, ezi recordings zathathwa iisampulu ukusuka kwiileya ezifanayo ze-cortical, ezikwi-ACx yokuqala endaweni yeendawo zesibini.
Ngokolwazi lwethu, impembelelo ye-LTE signaling kwiimpendulo ze-neuronal ayizange ixelwe ngaphambili. Nangona kunjalo, izifundo zangaphambili zibonise amandla e-GSM-1800 MHz okanye i-1800 MHz continuous wave (CW) okutshintsha uvuyo lwe-neuronal, nangona kukho umahluko omkhulu kuxhomekeke kwindlela yovavanyo. Kungekudala emva kokuvezwa kwi-1800 MHz CW kwinqanaba le-SAR le-8.2 W/Kg, iirekhodi ezivela kwi-snail ganglia zibonise ukwehla kwemida yokuqalisa amandla esenzo kunye nokuguqulwa kwe-neuronal. Kwelinye icala, umsebenzi wokutshiza kunye nokuqhuma kwiinkcubeko ze-neuronal eziphambili ezivela kwingqondo yegundane wehlisiwe ngokutyhileka kwi-GSM-1800 MHz okanye kwi-1800 MHz CW imizuzu eli-15 kwi-SAR ye-4.6 W/kg. Olu thintelo luguqulwe kancinci kwimizuzu engama-30 yokuvezwa. Ukuthuliswa okupheleleyo kwee-neurons kufezekiswe kwi-SAR ye-9.2 W/kg. Uhlalutyo lwempendulo yedosi lubonise ukuba i-GSM-1800 MHz yayisebenza ngakumbi kune-1800 MHz CW kwi ukuthintela umsebenzi wokuqhuma, nto leyo ebonisa ukuba iimpendulo ze-neuronal zixhomekeke ekuguqulweni kwesignali ye-RF.
Kwimeko yethu, iimpendulo ezivuswe yi-cortical zaqokelelwa kwi-vivo iiyure ezi-3 ukuya kwezi-6 emva kokuba ukuvezwa kwentloko kuphela kweeyure ezi-2 kuphelile. Kwisifundo sangaphambili, siphande ngesiphumo se-GSM-1800 MHz kwi-SARACx ye-1.55 W/kg kwaye asifumananga mpembelelo ibalulekileyo kwiimpendulo ze-cortical ezivuswe yisandi kwiimpuku eziphilileyo. Apha, isiphumo esibalulekileyo kuphela esivuswe kwiimpuku eziphilileyo ngokuchatshazelwa yi-LTE-1800 kwi-0.5 W/kg i-SARACx yayikukwanda okuncinci kwexesha lempendulo xa kuboniswa iithoni ezicocekileyo. Esi siphumo kunzima ukusichaza kuba asihambelani nokwanda kwamandla empendulo, nto leyo ebonisa ukuba eli xesha lempendulo elide lenzeka ngenani elifanayo lamandla esenzo akhutshwa yi-cortical neurons. Enye ingcaciso inokuba kukuba ukuvezwa kwe-LTE kunokunciphisa umsebenzi we-interneurons ezithile ezithintelayo, njengoko kubhaliwe ukuba kwi-ACx yokuqala ukuthintela ukuphefumla kulawula ixesha leempendulo ze-pyramidal cell ezibangelwa yi-excitatory thalamic input33,34, 35, 36, 37.
Ngokwahlukileyo koko, kwiimpuku ezihlaselwe yi-LPS-induggered neuroinflammation, ukuvezwa kwe-LTE akuzange kube nafuthe kwixesha lokudubula kwe-neuronal okubangelwa yisandi, kodwa iziphumo ezibalulekileyo zifunyenwe kumandla eempendulo ezivusiweyo. Enyanisweni, xa kuthelekiswa neempendulo ze-neuronal ezirekhodwe kwiimpuku ezivezwe yi-LPS-sham, ii-neurons kwiimpuku eziphathwe yi-LPS ezivezwe kwi-LTE zibonise ukwehla kobunzima beempendulo zazo, isiphumo esibonwayo xa kuboniswa iithoni ezimsulwa kunye nesandi sendalo. Ukuncipha kobunzima bempendulo kwiithoni ezimsulwa kwenzeke ngaphandle kokunciphisa i-bandwidth ye-spectral tuning ye-75 dB, kwaye ekubeni kwenzekile kuzo zonke i-intensities zesandi, kubangele ukwanda kwe-acoustic thresholds ye-cortical neurons kwi-frequency ephantsi nephakathi.
Ukuncipha kwamandla empendulo evuselelwe kubonise ukuba isiphumo se-LTE signaling kwi-SARACx ye-0.5 W/kg kwizilwanyana eziphathwe yi-LPS sasifana neso se-GSM-1800 MHz esisetyenziswa kwi-SARACx ephezulu ngokuphindwe kathathu (1.55 W/kg) 28. Ngokuphathelele i-GSM signaling, ukuvezwa kwentloko kwi-LTE-1800 MHz kunokunciphisa uvuyo lwe-neuronal kwi-neurons ze-ACx zegundane eziphantsi kwe-LPS-iggered neuroinflammation. Ngokuhambelana nale ngcamango, sikwabone umkhwa wokunciphisa ukuthembeka kwesilingo seempendulo ze-neuronal kwi-vocalization (Umzobo 4h) kunye nokunciphisa umsebenzi ozenzekelayo (Umzobo 4i). Nangona kunjalo, kube nzima ukumisela kwi-vivo ukuba i-LTE signaling inciphisa uvuyo lwe-neuronal okanye inciphisa igalelo le-synaptic, ngaloo ndlela ilawula iimpendulo ze-neuronal kwi-ACx.
Okokuqala, ezi mpendulo zibuthathaka zinokubangelwa kukuncipha kokuvuseleleka kweeseli ze-cortical emva kokuchaphazeleka kwi-LTE 1800 MHz. Ukuxhasa le ngcamango, i-GSM-1800 MHz kunye ne-1800 MHz-CW zinciphise umsebenzi wokuqhushumba xa zisetyenziswa ngokuthe ngqo kwiinkcubeko eziphambili zee-neurons ze-cortical rat kunye namanqanaba e-SAR angama-3.2 W/kg kunye ne-4.6 W/kg, ngokulandelanayo, kodwa inqanaba le-SAR elilinganiselweyo lalifuneka ukunciphisa kakhulu umsebenzi wokuqhushumba. Sikhuthaza ukunciphisa ukuvuseleleka kwangaphakathi, sikwabone amazinga aphantsi okudubula okuzenzekelayo kwizilwanyana ezityhilekileyo kunakwizilwanyana ezityhilekileyo.
Okwesibini, ukuvezwa kwe-LTE kunokuchaphazela ukudluliselwa kwe-synaptic ukusuka kwi-thalamo-cortical okanye i-cortical-cortical synapses. Iirekhodi ezininzi ngoku zibonisa ukuba, kwi-cortex yokuva, ububanzi bokulungiswa kwe-spectral abumiselwanga kuphela yi-afferent thalamic projections, kodwa ukuba uqhagamshelo lwe-intracortical lunika igalelo elongezelelweyo le-spectral kwiindawo ze-cortical39,40. Kwizilingo zethu, inyani yokuba i-cortical STRF ibonise ii-bandwidths ezifanayo kwizilwanyana ezivezweyo nezivezwe ngokungathanga ngqo icebisa ukuba iziphumo zokuvezwa kwe-LTE azizange zibe nefuthe kuqhagamshelo lwe-cortical-cortical. Oku kukwabonisa ukuba uqhagamshelo oluphezulu kwezinye iindawo ze-cortical ezivezwe kwi-SAR kunokuba zilinganiswe kwi-ACx (Umzobo 2) lusenokungabi noxanduva lweempendulo ezitshintshiweyo ezixelwe apha.
Apha, inxalenye enkulu yeerekhodi ze-cortical ezivezwe yi-LPS ibonise imilinganiselo ephezulu xa kuthelekiswa nezilwanyana ezivezwe yi-LPS-sham. Ngenxa yokuba kuye kwacetyiswa ukuba umda we-cortical acoustic ulawulwa kakhulu ngamandla e-thalamo-cortical synapse39,40, kunokucingelwa ukuba ukudluliselwa kwe-thalamo-cortical kuncitshiswa kancinci ngokuchatshazelwa, nokuba yi-presynaptic (ukukhululwa kwe-glutamate okuncitshisiweyo) okanye inqanaba le-postsynaptic (inani le-receptor elincitshisiweyo okanye i-affinity).
Ngokufanayo neziphumo ze-GSM-1800 MHz, iimpendulo ze-neuronal eziguqulwe yi-LTE zenzeke kwimeko ye-neuroinflammation ebangelwa yi-LPS, ebonakaliswa ziimpendulo ze-microglial. Ubungqina bangoku bubonisa ukuba i-microglia inefuthe elikhulu kumsebenzi we-neuronal networks kwiingqondo eziqhelekileyo nezine-pathological41,42,43. Amandla abo okuguqula i-neurotransmission axhomekeke kuphela kwimveliso yeekhompawundi abazivelisayo ezinokunciphisa okanye ezinokunciphisa i-neurotransmission, kodwa nakwi-motility ephezulu yeenkqubo zabo zeseli. Kwi-cerebral cortex, zombini umsebenzi owandisiweyo nowehliswayo we-neuronal networks ubangela ukwanda ngokukhawuleza kwendawo ye-microglial spatial domain ngenxa yokukhula kweenkqubo ze-microglial44,45. Ngokukodwa, ii-microglial protrusions zifunyanwa kufutshane ne-thalamocortical synapses esebenzayo kwaye zinokuthintela umsebenzi we-excitatory synapses ngeendlela ezibandakanya i-microglia-mediated local adenosine production.
Kwiimpuku eziphathwe yi-LPS ezithunyelwe kwi-GSM-1800 MHz nge-SARACx kwi-1.55 W/kg, ukwehla komsebenzi wee-neurons ze-ACx kwenzeke ngokukhula kweenkqubo ze-microglial eziphawulwe ziindawo ezibalulekileyo ezine-Iba1 kwi-ACx28 Increase. Olu phononongo lubonisa ukuba ukuhlaziywa kwe-microglial okubangelwa kukuvezwa yi-GSM kunokunceda ekunciphiseni okubangelwa yi-GSM kwiimpendulo ze-neuronal ezivuselelwa yisandi. Uphononongo lwethu lwangoku luphikisana nale ngcamango kwimeko yokuvezwa kwentloko ye-LTE nge-SARACx elinganiselwe kwi-0.5 W/kg, njengoko sifumene akukho kunyuka kwendawo egutyungelwe ziinkqubo ze-microglial. Nangona kunjalo, oku akuchasi naluphi na umphumo we-LTE signaling kwi-microglia esebenzayo ye-LPS, enokuchaphazela umsebenzi we-neuronal. Izifundo ezongezelelweyo ziyafuneka ukuphendula lo mbuzo kunye nokuchonga iindlela apho i-neuroinflammation ebukhali itshintsha ngayo iimpendulo ze-neuronal kwi-LTE signaling.
Ngokolwazi lwethu, impembelelo yemiqondiso ye-LTE ekucutshungulweni kwendlebe ayizange ifundwe ngaphambili. Izifundo zethu zangaphambili 26,28 kunye nophando lwangoku lubonise ukuba kwimeko yokuvuvukala okukhulu, ukuvezwa kwentloko yodwa kwi-GSM-1800 MHz okanye kwi-LTE-1800 MHz kubangele utshintsho olusebenzayo kwiimpendulo ze-neuronal kwi-ACx, njengoko kuboniswe kukwanda komda wokuva. Ubuncinane izizathu ezibini eziphambili, umsebenzi we-cochlear akufuneki uchaphazeleke kukuvezwa kwethu kwe-LTE. Okokuqala, njengoko kuboniswe kuphononongo lwe-dosimetry oluboniswe kuMfanekiso 2, amanqanaba aphezulu e-SAR (asondele kwi-1 W/kg) akwi-dorsomedial cortex (ngaphantsi kwe-antenna), kwaye ancipha kakhulu njengoko umntu ehamba ngakumbi ecaleni nangasecaleni. Inxalenye yentloko esecaleni. Inokuqikelelwa ukuba malunga ne-0.1 W/kg kwinqanaba le-pinna yegundane (ngaphantsi komjelo wendlebe). Okwesibini, xa iindlebe ze-guinea pig zivezwe iinyanga ezi-2 kwi-GSM 900 MHz (iintsuku ezi-5/iveki, iyure e-1/usuku, i-SAR phakathi kwe-1 kunye ne-4. W/kg), bekungekho tshintsho lubonakalayo kubukhulu bemveliso yokuphambuka kwe-otoacoustic Thresholds for Emission kunye ne-Auditory Brainstem Responses 47. Ngaphezu koko, ukuvezwa kwentloko okuphindaphindiweyo kwi-GSM 900 okanye i-1800 MHz kwi-SAR yendawo ye-2 W/kg akuzange kuchaphazele ukusebenza kweeseli zeenwele zangaphandle ze-cochlear kumagundane aphilileyo48,49. Ezi ziphumo zihambelana nedatha efunyenwe ebantwini, apho uphando lubonise ukuba ukuvezwa kwe-EMF yemizuzu eli-10 ukuya kwengama-30 kwiifowuni zeselula ze-GSM akunampembelelo iqhubekayo ekucutshungulweni kwendlebe njengoko kuhlolwe kwinqanaba le-cochlear50,51,52​okanye kwinqanaba le-brainstem53,54.
Kwisifundo sethu, utshintsho lokudubula kwe-neuronal olubangelwa yi-LTE lubonwe kwi-vivo iiyure ezi-3 ukuya kwezi-6 emva kokuba ukuvezwa kuphelile. Kwisifundo sangaphambili kwinxalenye ye-dorsomedial ye-cortex, iziphumo ezininzi ezibangelwe yi-GSM-1800 MHz ezibonwe kwiiyure ezingama-24 emva kokuba ukuvezwa azizange zibonwe kwiiyure ezingama-72 emva kokuvezwa. Oku kunjalo ngokwanda kweenkqubo ze-microglial, ukwehla kwe-IL-1ß gene kunye nokuguqulwa kwe-post-translational yee-receptors ze-AMPA. Xa sicinga ukuba i-cortex ye-auditory inexabiso eliphantsi le-SAR (0.5W/kg) kune-dorsomedial region (2.94W/kg26), utshintsho kumsebenzi we-neuronal oluchazwe apha lubonakala lungolwexeshana.
Idatha yethu kufuneka iqwalasele imida ye-SAR efanelekileyo kunye noqikelelo lwamaxabiso e-SAR afanelekileyo afunyenwe kwi-cortex ye-cerebral yabasebenzisi beefowuni eziphathwayo. Imigangatho yangoku esetyenziselwa ukukhusela uluntu imisela umda we-SAR ukuya kwi-2 W/kg yokuvezwa kwentloko okanye isifuba kwindawo ethile kwiifrikhwensi zerediyo kuluhlu lwe-100 kHz kunye ne-6 GHz RF.
Ukulinganisa idosi kwenziwe kusetyenziswa iimodeli ezahlukeneyo zentloko yomntu ukumisela ukufunxwa kwamandla e-RF kwizicubu ezahlukeneyo zentloko ngexesha lonxibelelwano lwentloko okanye lwefowuni ephathekayo. Ukongeza kulwahluko lweemodeli zentloko yomntu, ezi modeli zibonisa umahluko omkhulu okanye ukungaqiniseki ekuqikeleleni amandla afunxwa yingqondo ngokusekelwe kwiiparameter ze-anatomical okanye ze-histological ezifana nesimo sangaphandle okanye sangaphakathi sekhanda, ubukhulu, okanye umxholo wamanzi. Izicubu zentloko ezahlukeneyo zahluka kakhulu ngokweminyaka, isini, okanye umntu ngamnye 56,57,58. Ngaphezu koko, iimpawu zefowuni yeselula, ezifana nendawo yangaphakathi ye-antenna kunye nendawo yefowuni yeselula xa kuthelekiswa nentloko yomsebenzisi, zichaphazela kakhulu inqanaba kunye nokusasazwa kwamaxabiso e-SAR kwi-cortex yobuchopho 59,60. Nangona kunjalo, xa sicinga ngokusasazwa kwe-SAR okuxeliweyo kwi-cortex yobuchopho yomntu, okwasekwa kwiimodeli zefowuni yeselula ezikhupha amaza erediyo kuluhlu lwe-1800 MHz 58, 59, 60, kubonakala ngathi amanqanaba e-SAR afunyenwe kwi-cortex yokuqonda yomntu asasetyenziswa ngokwaneleyo isiqingatha se-cortex yobuchopho bomntu. Uphononongo lwethu (SARACx 0.5 W/kg). Ke ngoko, idatha yethu ayichasi imida yangoku yamaxabiso e-SAR asebenza kuluntu.
Ukuqukumbela, uphando lwethu lubonisa ukuba ukuvezwa kwi-LTE-1800 MHz ngentloko enye kuphela kuphazamisana neempendulo ze-neuronal zee-cortical neurons kwi-sensory stimuli. Ngokuhambelana neempawu zangaphambili zeziphumo ze-GSM signaling, iziphumo zethu zibonisa ukuba iziphumo ze-LTE signaling kumsebenzi we-neuronal ziyahluka ngokwemeko yempilo. Ukudumba kwe-neuroinflammation okukhawulezileyo kwenza ii-neurons zivakale kwi-LTE-1800 MHz, nto leyo ekhokelela ekutshintsheni kwe-cortical processing ye-auditory stimuli.
Idatha iqokelelwe xa sele zineentsuku ezingama-55 ubudala kwi-cerebral cortex yeempuku ezingama-31 ezingamadoda ezindala zeWistar ezifunyenwe kwilebhu yaseJanvier. Iimpuku zigcinwe kwindawo enomswakama (50-55%) kunye nobushushu (22-24 °C) kunye nomjikelo wokukhanya/umnyama weeyure ezili-12/12 (izibane zivuliwe ngentsimbi yesi-7:30am) kunye nokufikelela simahla ekutyeni nasemanzini. Zonke iimvavanyo zenziwe ngokuhambelana nezikhokelo ezisekwe yiBhunga leMibutho yaseYurophu (2010/63/EU Council Directive), ezifana nezo zichazwe kwiSociety for Neuroscience Guidelines for the Use of Animals in Neuroscience Research. Le protocol ivunyiwe yiKomiti yeMithetho yoBulungisa iParis-Sud kunye neZiko (CEEA N°59, iProjekthi 2014-25, iNational Protocol 03729.02) kusetyenziswa iinkqubo eziqinisekiswe yile komiti 32-2011 kunye 34-2012.
Izilwanyana zahlaliswa kwiindawo zokuhlala ubuncinane iveki e-1 ngaphambi kokuba unyango lwe-LPS luze luvezwe (okanye luvezwe ngokungeyonyani) kwi-LTE-EMF.
Iimpuku ezingamashumi amabini anesibini zifakwe i-intraperitoneally (ip) nge-E. coli LPS (250 µg/kg, serotype 0127:B8, SIGMA) exutywe ne-sterile endotoxin-free isotonic saline iiyure ezingama-24 ngaphambi kwe-LTE okanye ukuvezwa nge-sham (n ngeqela ngalinye). = 11).Kwiigundane ezingamadoda zeWistar ezineenyanga ezi-2 ubudala, olu nyango lwe-LPS luvelisa impendulo yokuvuvukala kwengqondo ephawulwe kwi-cortex yobuchopho ziijini ezininzi ezibangela ukuvuvukala (i-tumor necrosis factor-alpha, i-interleukin 1ß, i-CCL2, i-NOX2, i-NOS2) zanyuswa emva kweeyure ezingama-24 emva kokufakwa kwe-LPS, kubandakanya ukunyuka okuphindwe ka-4 kunye ne-12 kumanqanaba ee-transcripts ezifaka i-enzyme ye-NOX2 kunye ne-interleukin 1ß, ngokulandelanayo. Kweli xesha leeyure ezingama-24, i-cortical microglia ibonise imo yeseli "exineneyo" eqhelekileyo elindelwe kukuvuselelwa kwe-LPS okubangelwa kukuvuvukala kweeseli (Umfanekiso 1), okungafaniyo nokuvuselelwa kwe-LPS okubangelwa ngabanye. Ukuvuselelwa kwe-cell pro-inflammatory kuhambelana ne-24, 61.
Ukuvezwa entloko kuphela kwi-LTE EMF kwenziwe kusetyenziswa indlela yovavanyo eyayisetyenziswa ngaphambili ukuvavanya isiphumo se-GSM EMF26. Ukuvezwa kwe-LTE kwenziwe kwiiyure ezingama-24 emva kokufakwa kwe-LPS (izilwanyana ezili-11) okanye akukho nyango lwe-LPS (izilwanyana ezi-5). Izilwanyana zafakwa i-anesthesia kancinci nge-ketamine/xylazine (ketamine 80 mg/kg, ip; xylazine 10 mg/kg, ip) ngaphambi kokuvezwa ukuze kuthintelwe intshukumo kunye nokuqinisekisa ukuba intloko yesilwanyana yayikwi-antenna ye-loop ekhupha isignali ye-LTE Indawo ephinda ivele apha ngezantsi. Isiqingatha seempuku ezivela kwikheyiji enye zisebenza njengezilawuli (izilwanyana ezili-11 ezivezwe nge-sham, kwiimpuku ezingama-22 eziphathwe kwangaphambili nge-LPS): zabekwa phantsi kwe-antenna ye-loop kwaye amandla esignali ye-LTE abekwe kwi-zero. Ubunzima bezilwanyana ezivezwe nge-anesthesia kunye nezilwanyana ezivezwe nge-sham babufana (p = 0.558, uvavanyo lwe-t olungabhangqwanga, ns). Zonke izilwanyana ezivezwe nge-anesthesia zabekwa kwi-heating pad engenasinyithi ukugcina ubushushu bomzimba wazo malunga ne-37°C kulo lonke uvavanyo. Njengoko Kwizilingo zangaphambili, ixesha lokuvezwa lalimiselwe kwiiyure ezi-2. Emva kokuvezwa, beka isilwanyana kwenye i-heating pad kwigumbi lokutyanda. Inkqubo efanayo yokuvezwa yasetyenziswa kwiimpuku ezili-10 eziphilileyo (ezinganyangwanga nge-LPS), isiqingatha sazo savezwa kwikheyiji enye (p = 0.694).
Inkqubo yokuvezwa yayifana neenkqubo ezingama-25, 62 ezichazwe kwizifundo zangaphambili, apho ijenereyitha yerediyo itshintshiwe ukuze kuveliswe i-LTE endaweni yeentsimi ze-electromagnetic ze-GSM. Ngamafutshane, ijenereyitha ye-RF (SMBV100A, 3.2 GHz, Rohde & Schwarz, eJamani) ekhupha intsimi ye-electromagnetic ye-LTE - 1800 MHz iqhagamshelwe kwi-power amplifier (ZHL-4W-422+, Mini-Circuits, e-USA), i-circulator (D3 1719-N, eSodhy, eFransi), i-coupler eneendlela ezimbini (CD D 1824-2, − 30 dB, eSodhy, eFransi) kunye ne-power divider eneendlela ezine (DC D 0922-4N, eSodhy, eFransi), evumela ukuba kuvele izilwanyana ezine ngaxeshanye. Imitha yamandla (N1921A, e-Agilent, e-USA) eqhagamshelwe kwi-bidirectional coupler ivumele ukulinganiswa okuqhubekayo kunye nokubeka iliso kwesiganeko kwaye yabonakalisa amandla ngaphakathi kwesixhobo. Imveliso nganye iqhagamshelwe kwi-antenna ye-loop (Sama-Sistemi). srl; Roma), evumela ukuvezwa okuncinci kwentloko yesilwanyana. I-antenna yeluphu inesekethe eprintiweyo enemigca emibini yesinyithi (i-dielectric constant εr = 4.6) eqoshwe kwi-epoxy substrate ekhuselayo. Kwelinye icala, isixhobo siqulathe ucingo olububanzi obuyi-1 mm oluyakha isangqa esibekwe kufutshane nentloko yesilwanyana. Njengakwizifundo zangaphambili26,62, izinga lokufunxwa elithile (i-SAR) limiselwe ngokwenani kusetyenziswa imodeli yerayithi yamanani kunye nendlela ye-finite difference time domain (FDTD)63,64,65. Zikwamiselwe ngokwenani kwimodeli yerayithi ehambelanayo kusetyenziswa ii-Luxtron probes ukulinganisa ukunyuka kobushushu. Kule meko, i-SAR kwi-W/kg ibalwa kusetyenziswa ifomula: I-SAR = C ΔT/Δt, apho i-C ingumthamo wobushushu kwi-J/(kg K), ΔT, kwi-°K kunye ne-Δt Utshintsho lobushushu, ixesha ngemizuzwana. Amaxabiso e-SAR amiselwe ngokwenani athelekiswa namaxabiso e-SAR ovavanyo afunyenwe kusetyenziswa imodeli ehambelanayo, ngakumbi kwiindawo zobuchopho berayithi ezilinganayo. Umahluko phakathi kokulinganisa i-SAR yamanani kunye amaxabiso e-SAR afunyenwe ngovavanyo angaphantsi kwama-30%.
Umfanekiso 2a ubonisa ukusasazwa kwe-SAR kwingqondo yempuku kwimodeli yempuku, ehambelana nokusasazwa ngokwesisindo somzimba kunye nobukhulu beempuku ezisetyenzisiweyo kuphononongo lwethu. I-Brain average SAR yayiyi-0.37 ± 0.23 W/kg (i-average ± SD). Amaxabiso e-SAR aphezulu kwindawo ye-cortical engaphantsi nje kwe-antenna ye-loop. I-SAR yendawo kwi-ACx (SARACx) yayiyi-0.50 ± 0.08 W/kg (i-average ± SD) (Umzobo 2b). Ekubeni ubunzima bomzimba weempuku eziveziweyo bufana kwaye umahluko kubukhulu bezicubu zentloko awunamsebenzi, i-SAR yokwenyani ye-ACx okanye ezinye iindawo ze-cortical kulindeleke ukuba ifane kakhulu phakathi kwesilwanyana esinye esiveziweyo nesinye.
Ekupheleni kokuchatshazelwa, izilwanyana zongezelelwa ngeedosi ezongezelelweyo ze-ketamine (20 mg/kg, ip) kunye ne-xylazine (4 mg/kg, ip) de kungabikho ntshukumo ye-reflex ebonwe emva kokucinezela unyawo lwangasemva. I-anesthetic yendawo (i-Xylocain 2%) yafakwa ngaphantsi kwesikhumba nakwimisipha ye-temporalis ngaphezulu kwekhakayi, kwaye izilwanyana zafakwa kwinkqubo yokufudumeza engenasinyithi. Emva kokubeka isilwanyana kwisakhelo se-stereotaxic, kwenziwa i-craniotomy phezu kwe-cortex yasekhohlo ye-temporal. Njengakwisifundo sethu sangaphambili66, ukuqala kwindawo yokudibana kwamathambo e-parietal kunye nawe-temporal, ukuvulwa kwakungama-9 mm ububanzi kunye nokuphakama kwe-5 mm. I-dura engaphezulu kwe-ACx yasuswa ngononophelo phantsi kolawulo lwe-binocular ngaphandle kokonakalisa imithambo yegazi. Ekupheleni kwenkqubo, isiseko sakhiwe ngesamente ye-acrylic yamazinyo ukuze kulungiswe intloko yesilwanyana ngexesha lokurekhoda. Beka isakhelo se-stereotaxic esixhasa isilwanyana kwigumbi lokuthomalalisa i-acoustic (IAC, imodeli ye-AC1).
Idatha ifunyenwe kwiirekhodi zeeyunithi ezininzi kwi-primary auditory cortex yeempuku ezingama-20, kuquka nezilwanyana ezili-10 eziphathwe kwangaphambili nge-LPS. Iirekhodi ze-extracellular zifunyenwe kwii-electrodes ze-tungsten ezili-16 (TDT, ø: 33 µm, < 1 MΩ) eziqulathe imigca emibini yee-electrodes ezi-8 ezibekwe nge-1000 µm ngokwahlukeneyo (350 µm phakathi kwee-electrodes kumqolo omnye). Intambo yesilivere (ø: 300 µm) yokufaka umhlaba yafakwa phakathi kwethambo lexesha kunye ne-contralateral dura. Indawo eqikelelweyo ye-ACx ephambili yi-4-7 mm emva kwe-bregma kunye ne-3 mm ventral kwi-supratemporal suture. Isignali eluhlaza yandiswa amaxesha ali-10,000 (TDT Medusa) yaze yacutshungulwa yinkqubo yokufumana idatha ye-multi-channel (RX5, TDT). Izibonakaliso eziqokelelwe kwi-electrode nganye zahluzwa (610–10,000 Hz) ukuze kukhutshwe umsebenzi weeyunithi ezininzi. (MUA). Amanqanaba e-trigger amiselwe ngononophelo kwi-electrode nganye (ngababhali abasebenzisana nabo abangaboniyo kwiimeko ezivezwe okanye ezivezwe ngobuqhetseba) ukukhetha amandla amakhulu esenzo kwisignali. Ukuhlolwa kwe-intanethi kunye nokungafikeleli kwi-intanethi kweendlela zamaza kubonise ukuba i-MUA eqokelelwe apha yayine-action potentials eveliswa yi-neurons ezi-3 ukuya kwezi-6 kufutshane nee-electrodes. Ekuqaleni kovavanyo ngalunye, simisele indawo ye-electrode array ukuze imigca emibini yee-electrodes ezisibhozo ikwazi ukusampula ii-neurons, ukusuka kwiimpendulo ezisezantsi ukuya kweziphezulu xa zisenziwa kwi-rostral orientation.
Izinto ezivuselela isandi zenziwe kwiMatlab, zathunyelwa kwinkqubo yokuhanjiswa kwesandi esekelwe kwi-RP2.1 (TDT) zaza zathunyelwa kwisandisi-lizwi seFostex (FE87E). Isandisi-lizwi sabekwa kwi-2 cm ukusuka kwindlebe yasekunene yempuku, apho isandisi-lizwi savelisa i-flat frequency spectrum (± 3 dB) phakathi kwe-140 Hz kunye ne-36 kHz. Ukulinganiswa kwesandisi-lizwi kwenziwa kusetyenziswa ingxolo kunye neethoni ezicocekileyo ezirekhodwe nge-microphone yeBruel kunye neKjaer 4133 edityaniswe ne-preamplifier B&K 2169 kunye ne-digital recorder Marantz PMD671. I-Spectral Time Receptive Field (STRF) yamiselwa kusetyenziswa ii-gamma-tone frequencies ezingama-97, ezigubungela ii-octaves ezisi-8 (0.14–36 kHz), zamiselwa ngokulandelelana okungacwangciswanga kwi-75 dB SPL kwi-4.15 Hz. Indawo yempendulo yeFrequency (FRA) yamiselwa kusetyenziswa iseti efanayo yeethoni kwaye zaziswa ngokulandelelana okungacwangciswanga kwi-2 Hz ukusuka kwi-75 ukuya kwi-5 dB SPL. Ifrikhwensi nganye iboniswa izihlandlo ezisibhozo kubunzulu ngabunye.
Iimpendulo kwi-stimuli zendalo nazo zivavanyiwe. Kwizifundo zangaphambili, siqaphele ukuba i-vocalizations yegundane ayifane ivelise iimpendulo ezinamandla kwi-ACx, nokuba i-neuronal optimal frequency (BF), ngelixa i-xenograft-specific (umz., i-songbird okanye i-guinea pig vocalizations) idla ngokuba yimephu yethoni epheleleyo. Ke ngoko, sivavanye iimpendulo ze-cortical kwi-vocalizations kwi-guinea pigs (i-whistle esetyenziswe kwi-36 yayiqhagamshelwe kwi-1 s ye-stimuli, evezwe amaxesha angama-25).

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