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ʻO ke koi e hoʻonui mau nei no ke kamaʻilio kelepona paʻalima ua alakaʻi i ka puka mau ʻana o nā ʻenehana uea ʻole (G), kahi e loaʻa ai nā hopena like ʻole ma nā ʻōnaehana olaola. No ka hoʻāʻo ʻana i kēia, ua hōʻike mākou i nā ʻiole i kahi hōʻike poʻo hoʻokahi i kahi ulu lōʻihi 4G (LTE) -1800 MHz electromagnetic field (EMF) no 2 mau hola. A laila ua loiloi mākou i ka hopena o ka neuroinflammation acute i hoʻokomo ʻia e lipopolysaccharide ma ka uhi spatial microglia a me ka hana neuronal electrophysiological i loko o ka cortex auditory mua (ACx). ʻO ka awelika SAR ma ACx he 0.5 W/kg. Hōʻike nā hoʻopaʻa leo multi-unit e hoʻoulu ka LTE-EMF i ka hōʻemi ʻana i ka ikaika o ka pane ʻana i nā leo maʻemaʻe a me nā leo kūlohelohe, ʻoiai ka piʻi ʻana o ka paepae acoustic no nā alapine haʻahaʻa a me waena. ʻAʻole i hōʻike ka immunohistochemistry Iba1 i nā loli i ka wahi i uhi ʻia e nā kino microglial a me nā kaʻina hana. I loko o nā ʻiole olakino, ʻaʻole i hoʻoulu ka hōʻike LTE like i nā loli i ka ikaika pane a me nā paepae acoustic. Hōʻike kā mākou ʻikepili e hoʻonui ka neuroinflammation acute i nā neurons i LTE-EMF, e hopena ana i ka hoʻololi ʻana o ka hana ʻana o nā stimuli acoustic i loko. ACx.
Ua loli nui ke kaiapuni electromagnetic o ke kanaka i nā makahiki he kanakolu i hala iho nei ma muli o ka hoʻonui mau ʻana o nā kamaʻilio uea ʻole. I kēia manawa, ʻoi aku ma mua o ʻelua hapakolu o ka heluna kanaka i manaʻo ʻia he poʻe hoʻohana kelepona paʻalima (MP). ʻO ka laha nui ʻana o kēia ʻenehana ua hoʻāla i nā hopohopo a me ka hoʻopaʻapaʻa e pili ana i nā hopena weliweli o nā kahua electromagnetic pulsed (EMF) ma ka pae alapine lekiō (RF), i hoʻopuka ʻia e nā MP a i ʻole nā ​​​​kikowaena kumu a hoʻopili i nā kamaʻilio. Ua hoʻoikaika kēia pilikia olakino lehulehu i kekahi mau haʻawina hoʻokolohua i hoʻolaʻa ʻia no ka noiʻi ʻana i nā hopena o ka hoʻopili ʻana o ka radiofrequency i nā ʻiʻo olaola1. Ua ʻimi kekahi o kēia mau haʻawina i nā loli i ka hana pūnaewele neuronal a me nā kaʻina hana cognitive, i hāʻawi ʻia i ka kokoke o ka lolo i nā kumu RF ma lalo o ka hoʻohana nui ʻana o MP. Nui nā haʻawina i hōʻike ʻia e kamaʻilio ana i nā hopena o nā hōʻailona pulse modulated i hoʻohana ʻia ma ka ʻōnaehana honua lua o ka hanauna (2G) no nā kamaʻilio kelepona (GSM) a i ʻole ka wideband code division multiple access (WCDMA) / nā ʻōnaehana kelepona kelepona honua ʻekolu o ka hanauna (WCDMA/3G UMTS)2, 3,4,5. ʻAʻole ʻike nui ʻia e pili ana i nā hopena o nā hōʻailona alapine lekiō i hoʻohana ʻia ma nā lawelawe kelepona hanauna ʻehā (4G), e hilinaʻi nei i kahi Protocol Pūnaewele digital āpau. ʻenehana i kapa ʻia ʻo Long Term Evolution (LTE) ʻenehana. Hoʻokuʻu ʻia i ka makahiki 2011, manaʻo ʻia ka lawelawe kelepona LTE e hōʻea i 6.6 biliona mau mea kākau inoa LTE honua i Ianuali 2022 (GSMA: //gsacom.com). Ke hoʻohālikelike ʻia me nā ʻōnaehana GSM (2G) a me WCDMA (3G) e pili ana i nā papahana modulation lawe hoʻokahi, hoʻohana ʻo LTE i ka Orthogonal Frequency Division Multiplexing (OFDM) ma ke ʻano he ʻano hōʻailona kumu6. Ma ka honua holoʻokoʻa, hoʻohana nā lawelawe kelepona LTE i nā ʻano like ʻole o nā hui alapine like ʻole ma waena o 450 a me 3700 MHz, me nā hui 900 a me 1800 MHz i hoʻohana ʻia ma GSM.
ʻO ka hiki o ka hōʻike ʻana o RF e hoʻopilikia i nā kaʻina hana olaola e hoʻoholo nui ʻia e ka helu absorption kikoʻī (SAR) i hōʻike ʻia ma W/kg, kahi e ana ai i ka ikehu i hoʻopili ʻia i loko o nā ʻiʻo olaola. Ua ʻimi hou ʻia nā hopena o ka hōʻike ʻana o ke poʻo 30 mau minuke i nā hōʻailona LTE 2.573 GHz ma ka hana pūnaewele neuronal honua i nā mea manawaleʻa kanaka olakino. Ma ka hoʻohana ʻana i ka mokuʻāina hoʻomaha fMRI, ua ʻike ʻia hiki i ka hōʻike LTE ke hoʻoulu i nā loli pinepine lohi a me nā hoʻololi i ka pilina intra- a i ʻole inter-regional, ʻoiai ua manaʻo ʻia nā pae SAR kiʻekiʻe spatial ma luna o 10 g o nā ʻiʻo e loli ma waena o 0.42 a me 1.52 W/ kg, e like me nā kumuhana 7, 8, 9. Ua hōʻike ka loiloi EEG ma lalo o nā kūlana hōʻike like (30 min ka lōʻihi, ka pae SAR kiʻekiʻe i manaʻo ʻia he 1.34 W/kg me ka hoʻohana ʻana i kahi kumu hoʻohālike poʻo kanaka) i ka mana spectral i hoʻemi ʻia a me ka coherence hemispheric i nā hui alpha a me beta. Eia nō naʻe, ʻelua mau haʻawina ʻē aʻe e pili ana i ka loiloi EEG i ʻike ʻia he 20 a 30 mau minuke o ka hōʻike poʻo LTE, me nā pae SAR kūloko kiʻekiʻe loa i hoʻonohonoho ʻia ma kahi o 2 W/kg, ʻo ia hoʻi ʻaʻohe hopena i ʻike ʻia11 a i ʻole ua emi ka mana spectral i loko o ka alpha band, ʻoiai ʻaʻole i loli ka ʻike i ka hana i loiloi ʻia me ka hoʻāʻo Stroop 12. Ua ʻike ʻia nā ʻokoʻa koʻikoʻi i nā hopena o ka EEG a i ʻole nā ​​​​haʻawina cognitive e nānā pono ana i nā hopena o ka hōʻike ʻana o GSM a i ʻole UMTS EMF. Manaʻo ʻia lākou e kū mai ana mai nā ʻokoʻa o ka hoʻolālā ʻano hana a me nā ʻāpana hoʻokolohua, me ke ʻano hōʻailona a me ka modulation, ka ikaika o ka hōʻike a me ka lōʻihi, a i ʻole mai ka heterogeneity i nā kumuhana kanaka e pili ana i ka makahiki, anatomy, a i ʻole ke kāne.
A hiki i kēia manawa, ua hoʻohana ʻia kekahi mau haʻawina holoholona e hoʻoholo ai pehea ka hopena o ka hōʻike ʻana i ka hōʻailona LTE i ka hana o ka lolo. Ua hōʻike koke ʻia nei ʻo ka hōʻike ʻana o ka ʻiole e ulu ana mai ka wā embryonic hope loa a hiki i ka weaning (30 min/lā, 5 mau lā/pule, me ka awelika SAR kino holoʻokoʻa o 0.5 a i ʻole 1 W/kg) i hopena i nā ʻano neʻe a me ka makemake i ka wā makua 14. Ua ʻike ʻia ka hōʻike ʻana o ka ʻiole (2 ha i kēlā me kēia lā no 6 mau pule) i nā ʻiole makua e hoʻoulu i ke kaumaha oxidative a hoʻemi i ka nui o nā hiki ke hoʻoulu ʻia e ka ʻike maka i loaʻa mai ke aʻalolo optic, me ka SAR kiʻekiʻe loa i manaʻo ʻia he haʻahaʻa e like me 10 mW/kg15.
Ma waho aʻe o ka nānā ʻana ma nā unahi he nui, me nā pae cellular a me nā molekala, hiki ke hoʻohana ʻia nā hiʻohiʻona rodent e aʻo i nā hopena o ka hōʻike RF i ka wā o ka maʻi, e like me ka mea i kālele mua ʻia ma GSM a i ʻole WCDMA/3G UMTS EMF i loko o ka pōʻaiapili o ka neuroinflammation acute. Ua hōʻike nā haʻawina i nā hopena o nā hopu ʻana, nā maʻi neurodegenerative a i ʻole gliomas 16,17,18,19,20.
ʻO nā rodents i hoʻokomo ʻia i ka Lipopolysaccharide (LPS) he kumu hoʻohālike preclinical maʻamau o nā pane neuroinflammatory acute e pili ana i nā maʻi maʻi benign i hoʻokumu ʻia e nā virus a i ʻole bacteria e hoʻopilikia i ka hapa nui o ka heluna kanaka i kēlā me kēia makahiki. ʻO kēia kūlana mumū e alakaʻi i kahi maʻi hoʻohuli a me ka syndrome behavioral depressive i hōʻike ʻia e ke kuni, ka nalowale o ka makemake, a me ka hoʻemi ʻana i ka launa pū ʻana. ʻO nā phagocytes CNS noho e like me ka microglia nā cell effector koʻikoʻi o kēia pane neuroinflammatory. ʻO ka mālama ʻana i nā rodents me LPS e hoʻoulu ai i ka hoʻoulu ʻana o microglia i hōʻike ʻia e ka hana hou ʻana o ko lākou ʻano a me nā kaʻina hana cellular a me nā loli koʻikoʻi i ka ʻaoʻao transcriptome, me ka hoʻonui ʻana o nā genes e hoʻopili ana i nā cytokines pro-inflammatory a i ʻole nā ​​​​enzymes, e hoʻopilikia ana i nā pūnaewele neuronal Nā Hana 22, 23, 24.
Ma ke aʻo ʻana i nā hopena o ka hoʻolaha ʻana o ke poʻo he 2 hola i ka GSM-1800 MHz EMF i nā ʻiole i mālama ʻia e LPS, ua ʻike mākou ua hoʻoulu ka hōʻailona GSM i nā pane cellular i loko o ka cerebral cortex, e hoʻopilikia ana i ka hōʻike ʻana o ka gene, glutamate receptor phosphorylation, neuronal Meta-evoked firing a me ke ʻano o microglia i loko o ka cerebral cortex. ʻAʻole i ʻike ʻia kēia mau hopena i nā ʻiole olakino i loaʻa ka hōʻike GSM like, e hōʻike ana i ka mokuʻāina neuroinflammatory i hoʻoulu ʻia e LPS e hoʻonui i nā pūnaewele CNS i ka hōʻailona GSM. Ke kālele nei i ka auditory cortex (ACx) o nā ʻiole i mālama ʻia e LPS, kahi i awelika ai ka SAR kūloko he 1.55 W/kg, ua ʻike mākou ua hopena ka hōʻike ʻana o GSM i ka hoʻonui ʻana i ka lōʻihi a i ʻole ka lālā ʻana o nā kaʻina hana microglial a me ka emi ʻana o nā pane neuronal i hoʻoulu ʻia e nā leo maʻemaʻe a me .Natural Stimulation 28.
Ma ke aʻo ʻana o kēia manawa, ua manaʻo mākou e nānā inā hiki i ka hōʻike ʻana o ke poʻo wale nō i nā hōʻailona LTE-1800 MHz ke hoʻololi i ke ʻano microglial a me ka hana neuronal ma ACx, e hōʻemi ana i ka mana o ka hōʻike ʻana ma o ʻelua hapakolu. Ke hōʻike nei mākou ma ʻaneʻi ʻaʻohe hopena o ka hōʻailona LTE i nā kaʻina hana microglial akā ua hoʻoulu mau i ka emi nui ʻana o ka hana cortical i hoʻoulu ʻia e ke kani ma ka ACx o nā ʻiole i mālama ʻia me LPS me ka waiwai SAR o 0.5 W/kg.
Hāʻawi ʻia i nā hōʻike ma mua i hoʻololi ai ka hōʻike ʻana i ka GSM-1800 MHz i ke ʻano microglial ma lalo o nā kūlana pro-inflammatory, ua noiʻi mākou i kēia hopena ma hope o ka hōʻike ʻana i ka hōʻailona LTE.
Ua hoʻokomo ʻia nā ʻiole makua me ka LPS 24 mau hola ma mua o ka hōʻike ʻana i ke poʻo wale nō a i ʻole ka hōʻike ʻana i ka LTE-1800 MHz. Ma hope o ka hōʻike ʻana, ua hoʻokumu ʻia nā pane neuroinflammatory i hoʻoulu ʻia e LPS ma ka cortex cerebral, e like me ka mea i hōʻike ʻia e ka upregulation o nā genes proinflammatory a me nā loli i ke ʻano cortical microglia (Kiʻi 1). Ua hoʻonohonoho ʻia ka mana i hōʻike ʻia e ke poʻo LTE e loaʻa ai kahi pae SAR awelika o 0.5 W/kg ma ACx (Kiʻi 2). No ka hoʻoholo ʻana inā pane nā microglia i hoʻāla ʻia e LPS i ka LTE EMF, ua kālailai mākou i nā ʻāpana cortical i hoʻoluʻu ʻia me ka anti-Iba1 i koho pono ʻia i kēia mau cell. E like me ka mea i hōʻike ʻia ma ke Kiʻi 3a, ma nā ʻāpana ACx i hoʻopaʻa ʻia he 3 a 4 mau hola ma hope o ka hōʻike ʻana i ka sham a i ʻole LTE, ua like loa ke ʻano o ka microglia, e hōʻike ana i kahi morphology cell "dense-like" i hoʻoulu ʻia e ka LPS pro-inflammatory treatment (Kiʻi 1). E like me ka loaʻa ʻole o nā pane morphological, ʻaʻole i hōʻike ka nānā ʻana i ke kiʻi quantitative i nā ʻokoʻa koʻikoʻi ma ka ʻāpana holoʻokoʻa (unpaired t-test, p = 0.308) a i ʻole ka ʻāpana (p = 0.196) a me ka density (p = 0.061) o ka immunoreactivity Iba1 i ka hoʻohālikelike ʻana i ka hōʻike ʻana i nā kino cell Iba 1-stained i loko o nā ʻiole LTE e kūʻē i nā holoholona i hōʻike ʻia me ka hoʻopunipuni (Kiʻi 3b-d).
Nā hopena o ka hoʻokomo ʻana o LPS ip ma ke ʻano cortical microglia. ʻIke ʻelele o microglia ma kahi ʻāpana coronal o ka cerebral cortex (ʻāpana dorsomedial) 24 mau hola ma hope o ka hoʻokomo ʻana o LPS a i ʻole kaʻa (mana). Ua hoʻoluʻu ʻia nā cell me ka antibody anti-Iba1 e like me ka mea i wehewehe mua ʻia. ʻO ka mālama ʻana o LPS pro-inflammatory i hopena i nā loli i ke ʻano microglia, me ka hoʻomānoanoa proximal a me ka hoʻonui ʻana i nā lālā pōkole lua o nā kaʻina hana cellular, e hopena ana i kahi hiʻohiʻona "dense-like". Ka pā unahi: 20 µm.
ʻO ka loiloi dosimetric o ka helu absorption kikoʻī (SAR) i loko o ka lolo ʻiole i ka wā e hōʻike ʻia ai i ka 1800 MHz LTE. Ua hoʻohana ʻia kahi kumu hoʻohālike heterogeneous i wehewehe mua ʻia o ka phantom rat a me ka loop antenna62 e loiloi i ka SAR kūloko i loko o ka lolo, me kahi grid cubic 0.5 mm3.(a) ʻIke honua o kahi kumu hoʻohālike ʻiole i kahi hoʻonohonoho hōʻike me kahi antenna loop ma luna o ke poʻo a me kahi pad thermal metala (melemele) ma lalo o ke kino.(b) Ka hoʻolaha ʻana o nā waiwai SAR i loko o ka lolo makua ma ka hoʻonā spatial 0.5 mm3. ʻO ka wahi i hoʻokaʻawale ʻia e ka outline ʻeleʻele ma ka ʻāpana sagittal e pili ana i ka cortex auditory mua kahi e kālailai ʻia ai ka hana microglial a me neuronal. Pili ka pālākiō kala o nā waiwai SAR i nā simulations helu āpau i hōʻike ʻia ma ke kiʻi.
ʻO ka microglia i hoʻokomo ʻia i ka LPS i loko o ka cortex auditory rat ma hope o ka hōʻike ʻana iā LTE a i ʻole Sham. (a) ʻIke hoʻonohonoho ʻia o ka microglia i hoʻoluʻu ʻia me ka antibody anti-Iba1 i nā ʻāpana coronal o ka cortex auditory rat LPS-perfused 3 a 4 mau hola ma hope o ka hōʻike ʻana iā Sham a i ʻole LTE (hōʻike). Ka pā unahi: 20 µm. (bd) Loiloi morphometric o microglia 3 a 4 mau hola ma hope o ka sham (nā kiko hāmama) a i ʻole ka hōʻike ʻana iā LTE (hōʻike ʻia, nā kiko ʻeleʻele). (b, c) Uhi spatial (b) o ka māka microglia Iba1 a me nā wahi o nā kino cell Iba1-positive (c). Hōʻike ka ʻikepili i ka wahi hoʻoluʻu anti-Iba1 i hoʻomaʻamaʻa ʻia i ka awelika mai nā holoholona i hōʻike ʻia iā Sham. (d) Helu o nā kino cell microglial i hoʻoluʻu ʻia me ka anti-Iba1. ʻAʻole koʻikoʻi nā ʻokoʻa ma waena o nā holoholona Sham (n = 5) a me LTE (n = 6) (p > 0.05, unpaired t-test). ʻO ka luna a me lalo o ka pahu, ʻo nā laina luna a me lalo e hōʻike ana i ka 25th-75th percentile a me ka 5-95th percentile, kēlā me kēia. Ua hōʻailona ʻia ka waiwai awelika me ka ʻulaʻula i loko o ka pahu.
Hōʻuluʻulu ka Papa 1 i nā helu holoholona a me nā hoʻopaʻa leo multi-unit i loaʻa ma ka cortex auditory mua o ʻehā mau hui o nā ʻiole (Sham, Exposed, Sham-LPS, Exposed-LPS). Ma nā hopena ma lalo nei, hoʻokomo mākou i nā hoʻopaʻa leo āpau e hōʻike ana i kahi kahua hoʻokipa manawa spectral koʻikoʻi (STRF), ʻo ia hoʻi, nā pane leo-evoked ma ka liʻiliʻi he 6 mau deviations maʻamau ma mua o nā helu firing spontaneous (e nānā i ka Papa 1). Ke hoʻopili nei i kēia pae hoʻohālikelike, ua koho mākou i 266 mau moʻolelo no ka hui Sham, 273 mau moʻolelo no ka hui Exposed, 299 mau moʻolelo no ka hui Sham-LPS, a me 295 mau moʻolelo no ka hui Exposed-LPS.
Ma nā paukū aʻe, e wehewehe mua mākou i nā palena i unuhi ʻia mai ke kahua hoʻokipa spectral-temporal (ʻo ia hoʻi, ka pane i nā leo maʻemaʻe) a me ka pane i nā leo xenogeneic kikoʻī. A laila e wehewehe mākou i ka helu ʻana o ka ʻāpana pane alapine i loaʻa no kēlā me kēia hui. Ke noʻonoʻo nei i ke alo o ka "ʻikepili nested"30 i kā mākou hoʻolālā hoʻokolohua, ua hana ʻia nā loiloi helu āpau ma muli o ka helu o nā kūlana i loko o ka pūʻulu electrode (laina hope ma ka Papa 1), akā ʻo nā hopena āpau i wehewehe ʻia ma lalo nei ua hoʻokumu ʻia hoʻi ma ka helu o nā kūlana i kēlā me kēia hui. Ka huina o nā hoʻopaʻa leo multiunit i hōʻiliʻili ʻia (laina ʻekolu ma ka Papa 1).
Hōʻike ka Kiʻi 4a i ka hoʻolaha alapine kūpono (BF, e hoʻoulu ana i ka pane kiʻekiʻe loa ma 75 dB SPL) o nā neurons cortical i loaʻa ma Sham i mālama ʻia me LPS a me nā holoholona i hōʻike ʻia. Ua hoʻonui ʻia ka laulā alapine o BF ma nā hui ʻelua mai 1 kHz a i 36 kHz. Ua hōʻike ka loiloi helu ua like kēia mau hoʻolaha (chi-square, p = 0.278), e hōʻike ana e hiki ke hana i nā hoʻohālikelike ma waena o nā hui ʻelua me ka ʻole o ka bias sampling.
Nā hopena o ka hōʻike ʻana o ka LTE ma nā palena i helu ʻia o nā pane cortical i nā holoholona i mālama ʻia me ka LPS. (a) Ka hoʻolaha ʻana o BF i nā neurons cortical o nā holoholona i mālama ʻia me ka LPS i hōʻike ʻia i ka LTE (ʻeleʻele) a me ka hoʻopunipuni i hōʻike ʻia i ka LTE (keʻokeʻo). ʻAʻohe ʻokoʻa ma waena o nā hoʻolaha ʻelua. (bf) Ka hopena o ka hōʻike ʻana o ka LTE ma nā palena e helu ana i ke kahua hoʻokipa manawa spectral (STRF). Ua hoʻemi nui ʻia ka ikaika o ka pane (*p < 0.05, unpaired t-test) ma waena o STRF (ka ikaika pane holoʻokoʻa) a me nā alapine kūpono (b,c). Ka lōʻihi o ka pane, ka bandwidth pane, a me ka bandwidth constant (df). Ua hoʻemi ʻia ka ikaika a me ka hilinaʻi manawa o nā pane i nā leo leo (g, h). ʻAʻole i hoʻemi nui ʻia ka hana spontaneous (i). (*p < 0.05, unpaired t-test). (j,k) Nā hopena o ka hōʻike ʻana o ka LTE ma nā paepae cortical. ʻOi aku ka kiʻekiʻe o nā paepae awelika i nā ʻiole i hōʻike ʻia me ka LTE i hoʻohālikelike ʻia me nā ʻiole i hōʻike ʻia me ka hoʻopunipuni. ʻOi aku ka ʻike ʻia o kēia hopena ma nā alapine haʻahaʻa a me waena.
Hōʻike nā Kiʻi 4b-f i ka hoʻokaʻawale ʻana o nā palena i loaʻa mai ka STRF no kēia mau holoholona (nā ʻano i hōʻike ʻia e nā laina ʻulaʻula). ʻIke ʻia nā hopena o ka hōʻike ʻana o ka LTE ma nā holoholona i mālama ʻia me LPS e hōʻike ana i ka emi ʻana o ka hoʻonāukiuki neuronal. ʻO ka mea mua, ʻoi aku ka haʻahaʻa o ka ikaika o ka pane a me nā pane ma BF i hoʻohālikelike ʻia me nā holoholona Sham-LPS (Kiʻi 4b,c unpaired t-test, p = 0.0017; a me p = 0.0445). Pēlā nō, ua emi nā pane i nā leo kamaʻilio ma ka ikaika pane a me ka hilinaʻi ma waena o ka hoʻokolokolo (Kiʻi 4g,h; unpaired t-test, p = 0.043). Ua hoʻemi ʻia ka hana kūlohelohe, akā ʻaʻole koʻikoʻi kēia hopena (Kiʻi 4i; p = 0.0745). ʻAʻole i hoʻopilikia ʻia ka lōʻihi o ka pane, ka bandwidth tuning, a me ka latency pane e ka hōʻike LTE i nā holoholona i mālama ʻia me LPS (Kiʻi 4d–f), e hōʻike ana ʻaʻole i hoʻopilikia ʻia ke koho pinepine a me ka pololei o nā pane hoʻomaka e ka hōʻike LTE i nā holoholona i mālama ʻia me LPS.
Ua loiloi mākou ma hope inā ua hoʻololi ʻia nā paepae cortical leo maʻemaʻe e ka hōʻike LTE. Mai ka wahi pane alapine (FRA) i loaʻa mai kēlā me kēia hoʻopaʻa leo, ua hoʻoholo mākou i nā paepae lohe no kēlā me kēia alapine a ua awelika i kēia mau paepae no nā hui ʻelua o nā holoholona. Hōʻike ka Kiʻi 4j i nā paepae awelika (± sem) mai 1.1 a 36 kHz i nā ʻiole i mālama ʻia me LPS. ʻO ka hoʻohālikelike ʻana i nā paepae lohe o nā hui Sham a me Exposed i hōʻike i ka piʻi nui ʻana o nā paepae i nā holoholona i hōʻike ʻia i hoʻohālikelike ʻia me nā holoholona Sham (Kiʻi 4j), kahi hopena i ʻoi aku ka ʻike ʻia ma nā alapine haʻahaʻa a me waena. ʻOi aku ka pololei, ma nā alapine haʻahaʻa (< 2.25 kHz), ua piʻi ka hapa o nā neurons A1 me ka paepae kiʻekiʻe, ʻoiai ua emi ka hapa o nā neurons paepae haʻahaʻa a me waena (chi-square = 43.85; p < 0.0001; Kiʻi 4k, hema Kiʻi). Ua ʻike ʻia ka hopena like ma ka alapine waena (2.25 < Freq(kHz) < 11): kahi hapa kiʻekiʻe o nā hoʻopaʻa leo cortical me nā paepae waena a me kahi hapa liʻiliʻi o nā neurons me nā paepae haʻahaʻa i hoʻohālikelike ʻia me ka hui i hōʻike ʻole ʻia (Chi - Square = 71.17; p < 0.001; Kiʻi 4k, panela waena). Aia kekahi ʻokoʻa koʻikoʻi ma ka paepae no nā neurons alapine kiʻekiʻe (≥ 11 kHz, p = 0.0059); ua emi ka hapa o nā neurons paepae haʻahaʻa a ua piʻi ka hapa o ka paepae waena-kiʻekiʻe (chi-square = 10.853; p = 0.04 Kiʻi 4k, panela ʻākau).
Hōʻike ka Kiʻi 5a i ka hoʻolaha alapine kūpono (BF, e hoʻoulu ana i ka pane kiʻekiʻe loa ma 75 dB SPL) o nā neurons cortical i loaʻa i nā holoholona olakino no nā hui Sham a me Exposed. Ua hōʻike ka loiloi helu ua like nā hoʻolaha ʻelua (chi-square, p = 0.157), e hōʻike ana e hiki ke hana i nā hoʻohālikelike ma waena o nā hui ʻelua me ka ʻole o ka bias sampling.
Nā hopena o ka hōʻike ʻana o ka LTE ma nā palena i helu ʻia o nā pane cortical i nā holoholona olakino. (a) Ka hoʻolaha ʻana o BF i nā neurons cortical o nā holoholona olakino i hōʻike ʻia i ka LTE (uliuli ʻeleʻele) a me ka sham-hōʻike ʻia i ka LTE (uliuli māmā). ʻAʻohe ʻokoʻa ma waena o nā hoʻolaha ʻelua. (bf) Ka hopena o ka hōʻike ʻana o ka LTE ma nā palena e helu ana i ke kahua hoʻokipa manawa spectral (STRF). ʻAʻohe loli koʻikoʻi i ka ikaika o ka pane ma waena o ka STRF a me nā alapine kūpono (b,c). Aia kahi piʻi iki o ka lōʻihi o ka pane (d), akā ʻaʻohe loli i ka bandwidth pane a me ka bandwidth (e, f). ʻAʻole i loli ka ikaika a me ka hilinaʻi manawa o nā pane i nā leo (g, h). ʻAʻohe loli koʻikoʻi i ka hana spontaneous (i). (*p < 0.05 unpaired t-test). (j,k) Nā hopena o ka hōʻike ʻana o ka LTE ma nā paepae cortical. Ma ka awelika, ʻaʻole i loli nui nā paepae i nā ʻiole i hōʻike ʻia i ka LTE i hoʻohālikelike ʻia me nā ʻiole i hōʻike ʻia i ka Sham, akā ua haʻahaʻa iki nā paepae alapine kiʻekiʻe i nā holoholona i hōʻike ʻia.
Hōʻike nā Kiʻi 5b-f i nā pahu pahu e hōʻike ana i ka hoʻolaha a me ke ʻano (laina ʻulaʻula) o nā palena i loaʻa mai nā seti ʻelua o STRF. I nā holoholona olakino, ʻaʻole i loaʻa ka hopena liʻiliʻi o ka hōʻike ʻana o LTE iā ia iho ma ka waiwai awelika o nā palena STRF. Ke hoʻohālikelike ʻia me ka hui Sham (nā pahu mālamalama vs polū ʻeleʻele no ka hui i hōʻike ʻia), ʻaʻole i hoʻololi ka hōʻike ʻana o LTE i ka ikaika pane holoʻokoʻa a i ʻole ka pane ʻana o BF (Kiʻi 5b,c; unpaired t-test, p = 0.2176, a me p = 0.8696). ʻAʻohe hopena ma ka bandwidth spectral a me ka latency (p = 0.6764 a me p = 0.7129, kēlā me kēia), akā ua nui ka piʻi ʻana o ka lōʻihi o ka pane (p = 0.047). ʻAʻohe hopena ma ka ikaika o nā pane leo (Kiʻi 5g, p = 0.4375), ka hilinaʻi inter-trial o kēia mau pane (Kiʻi 5h, p = 0.3412), a me ka hana spontaneous (Kiʻi 5). 5i; p = 0.3256).
Hōʻike ka Kiʻi 5j i nā paepae awelika (± sem) mai 1.1 a 36 kHz i nā ʻiole olakino. ʻAʻole ia i hōʻike i kahi ʻokoʻa koʻikoʻi ma waena o ka sham a me nā ʻiole i hōʻike ʻia, koe wale nō ka paepae haʻahaʻa iki i nā holoholona i hōʻike ʻia ma nā alapine kiʻekiʻe (11-36 kHz) (unpaired t-test, p = 0.0083). Hōʻike kēia hopena i ka ʻoiaʻiʻo i nā holoholona i hōʻike ʻia, ma kēia pae alapine (chi-square = 18.312, p = 0.001; Kiʻi 5k), he nui iki nā neurons me nā paepae haʻahaʻa a me waena (ʻoiai nā paepae kiʻekiʻe) emi nā neurons).
I ka hopena, i ka wā i hōʻike ʻia ai nā holoholona olakino i ka LTE, ʻaʻohe hopena i ka ikaika o ka pane ʻana i nā leo maʻemaʻe a me nā leo paʻakikī e like me nā leo leo. Eia kekahi, i nā holoholona olakino, ua like nā paepae auditory cortical ma waena o nā holoholona i hōʻike ʻia a me nā holoholona hoʻopunipuni, ʻoiai i nā holoholona i mālama ʻia me LPS, ua hopena ka hōʻike ʻana o LTE i ka piʻi nui ʻana o nā paepae cortical, ʻoi aku hoʻi ma ka pae alapine haʻahaʻa a me ka waena.
Ua hōʻike kā mākou noiʻi i loko o nā ʻiole kāne makua e ʻike nei i ka neuroinflammation koʻikoʻi, ʻo ka ʻike ʻana iā LTE-1800 MHz me kahi SARACx kūloko o 0.5 W/kg (e ʻike i nā ʻAno Hana) ua hopena i ka emi nui ʻana o ka ikaika o nā pane i hoʻoulu ʻia e ke kani i nā hoʻopaʻa leo mua o ke kamaʻilio ʻana. Ua hana ʻia kēia mau loli i ka hana neuronal me ka ʻole o kahi loli maopopo i ka nui o ka ʻāpana spatial i uhi ʻia e nā kaʻina hana microglial. ʻAʻole i ʻike ʻia kēia hopena o LTE ma ka ikaika o nā pane cortical evoked i nā ʻiole olakino. Ke noʻonoʻo nei i ka like ʻana o ka hoʻolaha pinepine kūpono ma waena o nā ʻāpana hoʻopaʻa leo i nā holoholona LTE-exposed a me sham-exposed, hiki ke hoʻopili ʻia nā ʻokoʻa o ka hana neuronal i nā hopena olaola o nā hōʻailona LTE ma mua o ka sampling bias (Fig. 4a). Eia kekahi, ʻo ka loaʻa ʻole o nā loli i ka latency pane a me ka bandwidth tuning spectral i nā ʻiole LTE-exposed e hōʻike ana, ʻo ka mea paha, ua laʻana ʻia kēia mau hoʻopaʻa leo mai nā papa cortical like, aia ma ka ACx mua ma mua o nā ʻāpana lua.
I ko mākou ʻike, ʻaʻole i hōʻike mua ʻia ka hopena o ka hōʻailona LTE ma nā pane neuronal. Eia nō naʻe, ua hoʻopaʻa nā haʻawina mua i ka hiki o GSM-1800 MHz a i ʻole 1800 MHz continuous wave (CW) e hoʻololi i ka neuronal excitability, ʻoiai me nā ʻokoʻa koʻikoʻi ma muli o ke ʻano hoʻokolohua. Ma hope koke iho o ka hōʻike ʻana i ka 1800 MHz CW ma kahi pae SAR o 8.2 W/Kg, ua hōʻike nā hoʻopaʻa leo mai nā ganglia snail i nā paepae i emi iho no ka hoʻoulu ʻana i nā hana hana a me ka modulation neuronal. Ma ka ʻaoʻao ʻē aʻe, ua hoʻemi ʻia ka hana spiking a me ka bursting i nā moʻomeheu neuronal mua i loaʻa mai ka lolo ʻiole ma ka hōʻike ʻana i ka GSM-1800 MHz a i ʻole 1800 MHz CW no 15 mau minuke ma kahi SAR o 4.6 W/kg. Ua hoʻohuli hapa wale ʻia kēia inhibition i loko o 30 mau minuke o ka hōʻike ʻana. Ua hoʻokō ʻia ka hoʻopau piha ʻana o nā neurons ma kahi SAR o 9.2 W/kg. Ua hōʻike ka loiloi Dose-response ua ʻoi aku ka maikaʻi o GSM-1800 MHz ma mua o 1800 MHz CW i ka hoʻopau ʻana i ka hana burst, e hōʻike ana he neuronal hilinaʻi nā pane i ka modulation hōʻailona RF.
Ma kā mākou hoʻonohonoho ʻana, ua hōʻiliʻili ʻia nā pane i hoʻoulu ʻia e ka cortical i loko o ke kino i loko o 3 a 6 mau hola ma hope o ka pau ʻana o ka hōʻike ʻana o ke poʻo wale nō 2 hola. Ma kahi noiʻi mua, ua noiʻi mākou i ka hopena o GSM-1800 MHz ma SARACx o 1.55 W/kg a ʻaʻole i loaʻa kahi hopena koʻikoʻi i nā pane cortical i hoʻoulu ʻia e ke kani i nā ʻiole olakino. Maanei, ʻo ka hopena koʻikoʻi wale nō i hoʻoulu ʻia i nā ʻiole olakino ma o ka hōʻike ʻana iā LTE-1800 ma 0.5 W/kg SARACx he piʻi iki ia o ka lōʻihi o ka pane ma ka hōʻike ʻana o nā leo maʻemaʻe. He paʻakikī kēia hopena e wehewehe no ka mea ʻaʻole i hele pū ʻia me ka piʻi ʻana o ka ikaika o ka pane, e hōʻike ana e hana ʻia kēia lōʻihi o ka pane me ka huina like o nā hiki ke hana ʻia e nā neurons cortical. ʻO kekahi wehewehe paha, ʻo ka hōʻike ʻana o LTE e hōʻemi i ka hana o kekahi mau interneurons inhibitory, e like me ka mea i palapala ʻia ma ka ACx mua, kaohi ka inhibition feedforward i ka lōʻihi o nā pane cell pyramidal i hoʻoulu ʻia e ka excitatory thalamic input33,34, 35, 36, 37.
I ka hoʻohālikelike ʻana, i loko o nā ʻiole i hoʻokomo ʻia i ka neuroinflammation i hoʻoulu ʻia e LPS, ʻaʻohe hopena o ka hōʻike ʻana o LTE i ka lōʻihi o ke ahi neuronal i hoʻoulu ʻia e ke kani, akā ua ʻike ʻia nā hopena koʻikoʻi ma ka ikaika o nā pane i hoʻoulu ʻia. ʻO ka ʻoiaʻiʻo, i hoʻohālikelike ʻia me nā pane neuronal i hoʻopaʻa ʻia i loko o nā ʻiole i hōʻike ʻia e LPS-sham, ua hōʻike nā neurons i loko o nā ʻiole i mālama ʻia e LPS i hōʻike ʻia i ka LTE i ka emi ʻana o ka ikaika o kā lākou mau pane, kahi hopena i ʻike ʻia i ka wā e hōʻike ana i nā leo maʻemaʻe a me nā leo kūlohelohe. ʻO ka emi ʻana o ka ikaika o ka pane i nā leo maʻemaʻe i hana ʻia me ka ʻole o ka hoʻohaiki ʻana o ka bandwidth tuning spectral o 75 dB, a ʻoiai ua hana ʻia ma nā ikaika leo āpau, ua hopena ia i ka piʻi ʻana o nā paepae acoustic o nā neurons cortical ma nā alapine haʻahaʻa a me waena.
ʻO ka emi ʻana o ka ikaika o ka pane i hoʻāla ʻia e hōʻike ana ua like ka hopena o ka hōʻailona LTE ma SARACx o 0.5 W/kg i nā holoholona i mālama ʻia me LPS me ko GSM-1800 MHz i hoʻopili ʻia ma ʻekolu manawa kiʻekiʻe aʻe o SARACx (1.55 W/kg) 28. No ka hōʻailona GSM, ʻo ka hōʻike ʻana o ke poʻo i ka LTE-1800 MHz e hōʻemi paha i ka hoʻonāukiuki neuronal i nā neurons ACx iole i hoʻopilikia ʻia e ka neuroinflammation LPS. Ma ke ʻano o kēia kuhiakau, ua ʻike pū mākou i kahi ʻano e hōʻemi ana i ka hilinaʻi hoʻāʻo o nā pane neuronal i ka vocalization (Fig. 4h) a me ka emi ʻana o ka hana spontaneous (Fig. 4i). Eia nō naʻe, ua paʻakikī ke hoʻoholo i loko o vivo inā hōʻemi ka hōʻailona LTE i ka hoʻonāukiuki intrinsic neuronal a i ʻole e hōʻemi i ka hoʻokomo synaptic, no laila e kaohi ana i nā pane neuronal i ACx.
ʻO ka mea mua, ʻo kēia mau pane nāwaliwali paha ma muli o ka hoʻemi ʻia ʻana o ka excitability o nā cell cortical ma hope o ka hōʻike ʻana iā LTE 1800 MHz. Ke kākoʻo nei i kēia manaʻo, ua hoʻemi ʻo GSM-1800 MHz a me 1800 MHz-CW i ka hana pahū i ka wā i hoʻopili pololei ʻia i nā moʻomeheu mua o nā neurons cortical rat me nā pae SAR o 3.2 W/kg a me 4.6 W/kg, kēlā me kēia, akā ua koi ʻia kahi pae SAR paepae e hōʻemi nui i ka hana pahū. Ke kākoʻo nei no ka hoʻemi ʻia ʻana o ka excitability intrinsic, ua ʻike pū mākou i nā helu haʻahaʻa o ka puhi koke ʻana i nā holoholona i hōʻike ʻia ma mua o nā holoholona i hōʻike ʻia ma ke ʻano hoʻopunipuni.
ʻO ka lua, hiki i ka hōʻike ʻana o LTE ke hoʻopilikia i ka hoʻoili synaptic mai nā thalamo-cortical a i ʻole cortical-cortical synapses. Hōʻike nā moʻolelo he nui i kēia manawa, ma ka auditory cortex, ʻaʻole i hoʻoholo wale ʻia ka laulā o ka hoʻonohonoho spectral e nā projections thalamic afferent, akā hāʻawi nā pilina intracortical i ka hoʻokomo spectral hou i nā wahi cortical39,40. I kā mākou mau hoʻokolohua, ʻo ka ʻoiaʻiʻo ua hōʻike ʻo cortical STRF i nā bandwidths like i nā holoholona i hōʻike ʻia a me nā holoholona i hōʻike ʻia me ka sham i hōʻike pololei ʻole ʻia ʻaʻole nā ​​​​hopena o ka hōʻike LTE he hopena i ka pilina cortical-cortical. Hōʻike pū kēia i ka pilina kiʻekiʻe ma nā wahi cortical ʻē aʻe i hōʻike ʻia ma SAR ma mua o ke ana ʻia ma ACx (Fig. 2) ʻaʻole paha ke kuleana no nā pane i hoʻololi ʻia i hōʻike ʻia ma aneʻi.
Maanei, ʻo ka hapa nui o nā hoʻopaʻa leo cortical i hōʻike ʻia e LPS i hōʻike i nā paepae kiʻekiʻe i hoʻohālikelike ʻia me nā holoholona LPS-sham-exposed. No ka mea ua manaʻo ʻia ua kāohi nui ʻia ka paepae acoustic cortical e ka ikaika o ka thalamo-cortical synapse39,40, hiki ke kānalua ʻia ua hoʻemi hapa ʻia ka hoʻoili ʻana o thalamo-cortical e ka hōʻike ʻana, ʻo ia hoʻi ka presynaptic (hoʻemi ʻia ka hoʻokuʻu ʻana o ka glutamate) a i ʻole ka pae postsynaptic (hoʻemi ʻia ka helu receptor a i ʻole ka pilina).
E like me nā hopena o GSM-1800 MHz, ua hana ʻia nā pane neuronal i hoʻololi ʻia e LTE ma ke ʻano o ka neuroinflammation i hoʻoulu ʻia e LPS, i hōʻike ʻia e nā pane microglial. Hōʻike nā hōʻike o kēia manawa e hoʻoikaika nui ana ka microglia i ka hana o nā pūnaewele neuronal i loko o nā lolo maʻamau a me nā pathological41,42,43. ʻO ko lākou hiki ke hoʻololi i ka neurotransmission ʻaʻole ia e pili wale i ka hana ʻana o nā hui a lākou e hana ai e hiki ai ke kaupalena i ka neurotransmission, akā ma ke kiʻekiʻe o ka neʻe ʻana o kā lākou mau kaʻina hana cellular. I loko o ka cortex cerebral, ʻo ka hoʻonui ʻia a me ka emi ʻana o ka hana o nā pūnaewele neuronal e hoʻoulu ai i ka hoʻonui wikiwiki ʻana o ka microglial spatial domain ma muli o ka ulu ʻana o nā kaʻina hana microglial44,45. Ma ke ʻano kūikawā, ua hoʻolimalima ʻia nā protrusions microglial kokoke i nā synapses thalamocortical i hoʻāla ʻia a hiki ke kāohi i ka hana o nā synapses excitatory ma o nā mīkini e pili ana i ka hana adenosine kūloko i hoʻopili ʻia e microglia.
I loko o nā ʻiole i mālama ʻia me ka LPS i waiho ʻia i ka GSM-1800 MHz me SARACx ma 1.55 W/kg, ua emi ka hana o nā neurons ACx me ka ulu ʻana o nā kaʻina hana microglial i hōʻailona ʻia e nā wahi koʻikoʻi i hoʻoluʻu ʻia e Iba1 ma ka ACx28 Increase. Hōʻike kēia ʻike e hiki i ka hoʻoponopono hou ʻana o ka microglial i hoʻoulu ʻia e ka hōʻike ʻana o GSM ke kōkua ikaika i ka hōʻemi ʻana o ka GSM i nā pane neuronal i hoʻoulu ʻia e ke kani. Ke kūʻē nei kā mākou noiʻi o kēia manawa i kēia kuhiakau ma ke ʻano o ka hōʻike ʻana o ke poʻo LTE me SARACx i kaupalena ʻia i 0.5 W/kg, ʻoiai ʻaʻole mākou i ʻike i ka hoʻonui ʻana i ka ʻāpana spatial i uhi ʻia e nā kaʻina hana microglial. Eia naʻe, ʻaʻole kēia e kāpae i kekahi hopena o ka hōʻailona LTE ma ka microglia i hoʻāla ʻia e LPS, kahi e hoʻopilikia ai i ka hana neuronal. Pono nā haʻawina hou aʻe e pane i kēia nīnau a e hoʻoholo i nā ʻano hana e hoʻololi ai ka neuroinflammation acute i nā pane neuronal i ka hōʻailona LTE.
I ko mākou ʻike, ʻaʻole i aʻo ʻia ka hopena o nā hōʻailona LTE ma ke kaʻina hana hoʻolohe ma mua. Ua hōʻike kā mākou mau haʻawina mua 26,28 a me ke aʻo ʻana o kēia manawa i ke ʻano o ka mumū koʻikoʻi, ʻo ka hōʻike ʻana o ke poʻo wale nō iā GSM-1800 MHz a i ʻole LTE-1800 MHz i hopena i nā hoʻololi hana i nā pane neuronal ma ACx, e like me ka mea i hōʻike ʻia e ka piʻi ʻana o ka paepae lohe. No nā kumu nui ʻelua ma ka liʻiliʻi, ʻaʻole pono e hoʻopilikia ʻia ka hana cochlear e kā mākou hōʻike LTE. ʻO ka mea mua, e like me ka mea i hōʻike ʻia ma ke aʻo dosimetry i hōʻike ʻia ma ke Kiʻi 2, aia nā pae kiʻekiʻe loa o SAR (kokoke i 1 W/kg) ma ka cortex dorsomedial (ma lalo o ka antenna), a emi nui lākou i ka neʻe ʻana o kekahi ma ka ʻaoʻao a me ka ʻaoʻao. ʻO ka ʻāpana ventral o ke poʻo. Hiki ke manaʻo ʻia he 0.1 W/kg ma ka pae o ka pinna rat (ma lalo o ke kahawai pepeiao). ʻO ka lua, i ka wā i hōʻike ʻia ai nā pepeiao puaʻa guinea no 2 mau mahina ma GSM 900 MHz (5 mau lā/pule, 1 hola/lā, SAR ma waena o 1 a me 4 W/kg), aia ʻaʻohe loli i ʻike ʻia i ka nui o ka huahana distortion otoacoustic Thresholds for Emission and Auditory Brainstem Responses 47. Eia kekahi, ʻo ka hoʻopili pinepine ʻana o ke poʻo i ka GSM 900 a i ʻole 1800 MHz ma kahi SAR kūloko o 2 W/kg ʻaʻole i hoʻopilikia i ka hana o nā cell lauoho waho cochlear i nā ʻiole olakino 48,49. Hōʻike kēia mau hopena i ka ʻikepili i loaʻa i loko o ke kanaka, kahi i hōʻike ai nā noiʻi ʻaʻohe hopena mau o ka hoʻopili ʻana o 10- a 30-minuke i ka EMF mai nā kelepona paʻalima GSM i ka hana auditory e like me ka loiloi ʻana ma ka cochlear 50,51,52​​a i ʻole ka pae brainstem 53,54.
Ma kā mākou noiʻi, ua ʻike ʻia nā loli hoʻā neuronal i hoʻoulu ʻia e LTE i loko o vivo 3 a 6 mau hola ma hope o ka pau ʻana o ka hōʻike ʻana. Ma kahi noiʻi mua ma ka ʻāpana dorsomedial o ka cortex, ʻaʻole ʻike hou ʻia kekahi mau hopena i hoʻokumu ʻia e GSM-1800 MHz i ʻike ʻia ma 24 mau hola ma hope o ka hōʻike ʻana ma 72 mau hola ma hope o ka hōʻike ʻana. ʻO kēia ke ʻano me ka hoʻonui ʻana o nā kaʻina hana microglial, ka hoʻohaʻahaʻa ʻana o ka gene IL-1ß a me ka hoʻololi ʻana ma hope o ka unuhi ʻana o nā mea loaʻa AMPA. Ke noʻonoʻo nei he haʻahaʻa ka waiwai SAR o ka auditory cortex (0.5W/kg) ma mua o ka ʻāina dorsomedial (2.94W/kg26), ʻike ʻia nā loli i ka hana neuronal i hōʻike ʻia ma ʻaneʻi he transient.
Pono kā mākou ʻikepili e noʻonoʻo i nā palena SAR kūpono a me nā kuhi o nā waiwai SAR maoli i loaʻa i loko o ka cortex cerebral o nā mea hoʻohana kelepona paʻalima. ʻO nā kūlana o kēia manawa i hoʻohana ʻia e pale aku i ka lehulehu e hoʻonohonoho i ka palena SAR i 2 W/kg no ka ʻike ʻana o ke poʻo a i ʻole ke kino i nā alapine lekiō ma ka pae RF 100 kHz a me 6 GHz.
Ua hana ʻia nā simulations dosage me ka hoʻohana ʻana i nā hiʻohiʻona poʻo kanaka like ʻole e hoʻoholo ai i ka omo ʻana o ka mana RF i nā ʻiʻo like ʻole o ke poʻo i ka wā o ke kamaʻilio ʻana o ke poʻo maʻamau a i ʻole ke kelepona paʻalima. Ma waho aʻe o ke ʻano like ʻole o nā hiʻohiʻona poʻo kanaka, hōʻike kēia mau simulations i nā ʻokoʻa koʻikoʻi a i ʻole nā ​​​​​​mea kānalua i ka helu ʻana i ka ikehu i omo ʻia e ka lolo ma muli o nā ʻano anatomical a histological paha e like me ke ʻano o waho a i loko paha o ke poʻo, ka mānoanoa, a i ʻole ka nui o ka wai. ʻOkoʻa loa nā ʻiʻo poʻo like ʻole e like me ka makahiki, ke kāne, a i ʻole ke kanaka 56,57,58. Eia kekahi, ʻo nā ʻano kelepona paʻalima, e like me ke kūlana o loko o ka antenna a me ke kūlana o ke kelepona paʻalima e pili ana i ke poʻo o ka mea hoʻohana, e hoʻohuli ikaika i ka pae a me ka hoʻolaha ʻana o nā waiwai SAR i loko o ka cerebral cortex 59,60. Eia nō naʻe, i ka noʻonoʻo ʻana i nā hoʻolaha SAR i hōʻike ʻia ma ka cerebral cortex kanaka, i hoʻokumu ʻia mai nā hiʻohiʻona kelepona paʻalima e hoʻopuka ana i nā alapine lekiō ma ka pae 1800 MHz 58, 59, 60, ʻike ʻia ʻo nā pae SAR i loaʻa i loko o ka auditory cortex kanaka he hapalua wale nō o ka cerebral cortex kanaka. ʻO kā mākou noiʻi (SARACx 0.5 W/kg). No laila, ʻaʻole e hoʻopiʻi kā mākou ʻikepili i nā palena o kēia manawa o nā waiwai SAR e pili ana i ka lehulehu.
I ka hopena, hōʻike kā mākou noiʻi ʻana he hoʻokahi wale nō poʻo o ka hōʻike ʻana i ka LTE-1800 MHz e hoʻopilikia i nā pane neuronal o nā neurons cortical i nā stimuli sensory. E like me nā ʻano mua o nā hopena o ka hōʻailona GSM, hōʻike kā mākou mau hopena e ʻokoʻa nā hopena o ka hōʻailona LTE ma ka hana neuronal ma ke kūlana olakino. Hoʻonui ka neuroinflammation acute i nā neurons i ka LTE-1800 MHz, e hopena ana i ka hoʻololi ʻana o ka hana cortical o nā stimuli auditory.
Ua hōʻiliʻili ʻia nā ʻikepili i 55 mau lā o ka makahiki mai ka cortex cerebral o 31 mau ʻiole kāne Wistar makua i loaʻa ma ka hale hana ʻo Janvier. Ua hoʻokomo ʻia nā ʻiole i loko o kahi hale i kāohi ʻia e ka haʻahaʻa (50-55%) a me ka mahana (22-24 °C) me kahi pōʻaiapuni mālamalama/pouli o 12 h/12 ​​​​h (nā kukui e hoʻā ana i ka hola 7:30am) me ke komo manuahi ʻana i ka meaʻai a me ka wai. Ua hana ʻia nā hoʻokolohua āpau e like me nā alakaʻi i hoʻokumu ʻia e ka ʻAha Kūkākūkā o nā Kaiāulu ʻEulopa (2010/63/EU Council Directive), e like me nā mea i wehewehe ʻia ma ka Society for Neuroscience Guidelines for the Use of Animals in Neuroscience Research. Ua ʻae ʻia kēia protocol e ke Komite Ethics Paris-Sud a me Center (CEEA N°59, Project 2014-25, National Protocol 03729.02) me ka hoʻohana ʻana i nā kaʻina hana i hōʻoia ʻia e kēia komite 32-2011 a me 34-2012.
Ua hoʻomaʻamaʻa ʻia nā holoholona i nā keʻena kolone no ka liʻiliʻi he 1 pule ma mua o ka mālama ʻana iā LPS a me ka hōʻike ʻana (a i ʻole ka hōʻike hoʻopunipuni) iā LTE-EMF.
Ua hoʻokomo ʻia he iwakāluakūmālua mau ʻiole i loko o ka ʻōpū (ip) me ka E. coli LPS (250 µg/kg, serotype 0127:B8, SIGMA) i hoʻoheheʻe ʻia me ka sterile endotoxin-free isotonic saline 24 mau hola ma mua o ka LTE a i ʻole ka hoʻolaha ʻana i ka sham (n no kēlā me kēia hui). = 11). I loko o nā ʻiole kāne Wistar 2 mahina, ua hoʻopuka kēia lāʻau LPS i kahi pane neuroinflammatory i hōʻailona ʻia ma ka cortex cerebral e kekahi mau genes pro-inflammatory (tumor necrosis factor-alpha, interleukin 1ß, CCL2, NOX2, NOS2) i hoʻonui ʻia i 24 mau hola ma hope o ka hoʻokomo ʻana o LPS, me ka hoʻonui ʻana o 4- a me 12-fold i nā pae o nā transcripts e hoʻopili ana i ka enzyme NOX2 a me interleukin 1ß, kēlā me kēia. I kēia manawa 24-h, ua hōʻike ka cortical microglia i ke ʻano cell "dense" maʻamau i manaʻo ʻia e ka LPS-triggered pro-inflammatory activation o nā cell (Kiʻi 1), kahi i kūʻē i ka LPS-triggered activation e nā poʻe ʻē aʻe. ʻO ka hoʻoulu ʻana o ka pro-inflammatory cellular e pili ana i 24, 61.
Ua hana ʻia ka hōʻike ʻana i ke poʻo wale nō i ka LTE EMF me ka hoʻohana ʻana i ka hoʻonohonoho hoʻokolohua i hoʻohana mua ʻia e loiloi i ka hopena o GSM EMF26. Ua hana ʻia ka hōʻike ʻana i ka LTE 24 mau hola ma hope o ka hoʻokomo ʻana o LPS (11 mau holoholona) a i ʻole ka lāʻau LPS ʻole (5 mau holoholona). Ua hoʻomaʻamaʻa māmā ʻia nā holoholona me ketamine/xylazine (ketamine 80 mg/kg, ip; xylazine 10 mg/kg, ip) ma mua o ka hōʻike ʻana e pale i ka neʻe ʻana a e hōʻoia i ke poʻo o ka holoholona i loko o ka antenna loop e hoʻopuka ana i ka hōʻailona LTE Kahi hana hou ma lalo. ʻO ka hapalua o nā ʻiole mai ka hale like i lawelawe ʻia ma ke ʻano he mau kaohi (11 mau holoholona i hōʻike ʻia me ka sham, mai loko mai o 22 mau ʻiole i mālama mua ʻia me LPS): ua kau ʻia lākou ma lalo o ka antenna loop a ua hoʻonohonoho ʻia ka ikehu o ka hōʻailona LTE i ka ʻole. Ua like nā kaumaha o nā holoholona i hōʻike ʻia a me nā holoholona i hōʻike ʻia me ka sham (p = 0.558, unpaired t-test, ns). Ua kau ʻia nā holoholona i hoʻomaʻamaʻa ʻia a pau ma luna o kahi pad hoʻomehana metala ʻole e mālama i ko lākou mahana kino ma kahi o 37 ° C ma o ka hoʻokolohua. E like me ka Ma nā hoʻokolohua ma mua, ua hoʻonohonoho ʻia ka manawa hōʻike i 2 mau hola. Ma hope o ka hōʻike ʻana, e kau i ka holoholona ma luna o kahi pā hoʻomehana ʻē aʻe i loko o ka lumi hana. Ua hoʻopili ʻia ke kaʻina hana hōʻike like i 10 mau ʻiole olakino (ʻaʻole i mālama ʻia me LPS), ʻo ka hapalua o ia mau mea i hōʻike hoʻopunipuni ʻia mai ka hale like (p = 0.694).
Ua like ka ʻōnaehana hōʻike me nā ʻōnaehana 25, 62 i wehewehe ʻia ma nā haʻawina mua, me ka mea hana alapine lekiō i pani ʻia e hana i ka LTE ma kahi o nā kahua electromagnetic GSM. I ka pōkole, ua hoʻopili ʻia kahi mea hana RF (SMBV100A, 3.2 GHz, Rohde & Schwarz, Kelemānia) e hoʻopuka ana i kahi kahua electromagnetic LTE - 1800 MHz i kahi mea hoʻonui mana (ZHL-4W-422+, Mini-Circuits, USA), kahi circulator (D3 1719-N, Sodhy, Palani), kahi mea hoʻohui ʻelua ala (CD D 1824-2, − 30 dB, Sodhy, Palani) a me kahi mea hoʻokaʻawale mana ʻehā ala (DC D 0922-4N, Sodhy, Palani), e ʻae ana i ka Expose i ʻehā mau holoholona i ka manawa like. ʻO kahi mika mana (N1921A, Agilent, USA) i hoʻopili ʻia i kahi mea hoʻohui bidirectional i ʻae i ke ana mau a me ka nānā ʻana i ka mana hanana a me ka mana i hōʻike ʻia i loko o ka hāmeʻa. Ua hoʻopili ʻia kēlā me kēia hopena i kahi antenna loop (Sama-Sistemi srl; Roma), e hiki ai ke hōʻike hapa ʻia ke poʻo o ka holoholona. ʻO ka antenna loop he kaapuni paʻi me ʻelua mau laina metala (dielectric constant εr = 4.6) i kālai ʻia ma luna o kahi substrate epoxy insulating. Ma kekahi ʻaoʻao, aia ka hāmeʻa he uea 1 mm ākea e hana ana i kahi apo i kau ʻia kokoke i ke poʻo o ka holoholona. E like me nā haʻawina ma mua26,62, ua hoʻoholo ʻia ka helu absorption kikoʻī (SAR) ma ka helu me ka hoʻohana ʻana i kahi kumu hoʻohālike helu helu a me kahi ʻano manawa palena ʻokoʻa (FDTD)63,64,65. Ua hoʻoholo pū ʻia lākou ma ka hoʻokolohua ma kahi kumu hoʻohālike homogeneous rat me ka hoʻohana ʻana i nā probes Luxtron e ana i ka piʻi ʻana o ka mahana. I kēia hihia, ua helu ʻia ʻo SAR ma W/kg me ka hoʻohana ʻana i ke ʻano: SAR = C ΔT/Δt, kahi ʻo C ka mana wela ma J/(kg K), ΔT, ma °K a me Δt Hoʻololi mahana, manawa ma kekona. Ua hoʻohālikelike ʻia nā waiwai SAR i hoʻoholo ʻia me nā waiwai SAR hoʻokolohua i loaʻa me ka hoʻohana ʻana i kahi kumu hoʻohālike homogeneous, ʻoi aku hoʻi ma nā wahi lolo ʻiole like. ʻO ka ʻokoʻa ma waena o nā ana SAR helu a me nā waiwai SAR i ʻike ʻia e ka hoʻokolohua ʻoi aku ka liʻiliʻi ma mua o 30%.
Hōʻike ka Kiʻi 2a i ka hoʻolaha SAR i loko o ka lolo ʻiole i loko o ke kumu hoʻohālike ʻiole, kahi e kūlike me ka hoʻolaha ma ke ʻano o ke kaumaha o ke kino a me ka nui o nā ʻiole i hoʻohana ʻia i kā mākou noiʻi. ʻO ka awelika o ka lolo SAR he 0.37 ± 0.23 W/kg (awelika ± SD). ʻOi aku ka kiʻekiʻe o nā waiwai SAR ma ka ʻāpana cortical ma lalo pono o ka antenna loop. ʻO ka SAR kūloko ma ACx (SARACx) he 0.50 ± 0.08 W/kg (awelika ± SD) (Kiʻi 2b). ʻOiai he like nā kaumaha o ke kino o nā ʻiole i hōʻike ʻia a he mea liʻiliʻi nā ʻokoʻa o ka mānoanoa o ke poʻo, manaʻo ʻia ka SAR maoli o ACx a i ʻole nā ​​​​wahi cortical ʻē aʻe e like loa ma waena o kekahi holoholona i hōʻike ʻia a me kekahi.
I ka hopena o ka hōʻike ʻana, ua hoʻohui ʻia nā holoholona me nā dosis hou o ketamine (20 mg/kg, ip) a me xylazine (4 mg/kg, ip) a hiki i ka ʻike ʻole ʻia o nā neʻe reflex ma hope o ke kuʻi ʻana i ka wāwae hope. Ua hoʻokomo ʻia kahi anesthetic kūloko (Xylocain 2%) ma ke ʻano subcutaneous i loko o ka ʻili a me ka ʻiʻo temporalis ma luna o ke poʻo, a ua kau ʻia nā holoholona ma luna o kahi ʻōnaehana hoʻomehana metala ʻole. Ma hope o ke kau ʻana i ka holoholona i loko o ke kiʻi stereotaxic, ua hana ʻia kahi craniotomy ma luna o ka cortex temporal hema. E like me kā mākou noiʻi mua66, e hoʻomaka ana mai ka hui ʻana o nā iwi parietal a me ka temporal, ʻo ka puka he 9 mm ka laulā a me 5 mm ke kiʻekiʻe. Ua wehe pono ʻia ka dura ma luna o ka ACx ma lalo o ka mana binocular me ka hōʻino ʻole i nā kīʻaha koko. I ka hopena o ke kaʻina hana, ua kūkulu ʻia kahi kumu i loko o ka sima acrylic niho no ka hoʻopaʻa ʻana o ke poʻo o ka holoholona i ka wā e hoʻopaʻa ai. E kau i ke kiʻi stereotaxic e kākoʻo ana i ka holoholona i loko o kahi keʻena attenuation acoustic (IAC, kumu hoʻohālike AC1).
Ua loaʻa nā ʻikepili mai nā hoʻopaʻa leo multi-unit i loko o ka cortex auditory mua o 20 mau ʻiole, me 10 mau holoholona i mālama mua ʻia me LPS. Ua loaʻa nā hoʻopaʻa leo extracellular mai kahi pūʻulu o 16 mau electrodes tungsten (TDT, ø: 33 µm, < 1 MΩ) i haku ʻia me ʻelua lālani o 8 mau electrodes i hoʻokaʻawale ʻia he 1000 µm kaʻawale (350 µm ma waena o nā electrodes i ka lālani hoʻokahi). Ua hoʻokomo ʻia kahi uea kālā (ø: 300 µm) no ka hoʻokumu ʻana ma waena o ka iwi temporal a me ka dura contralateral. ʻO kahi i manaʻo ʻia o ka ACx mua he 4-7 mm ma hope o ka bregma a me 3 mm ventral i ka suture supratemporal. Ua hoʻonui ʻia ka hōʻailona maka i 10,000 mau manawa (TDT Medusa) a laila hana ʻia e kahi ʻōnaehana loaʻa ʻikepili multi-channel (RX5, TDT). Ua kānana ʻia nā hōʻailona i hōʻiliʻili ʻia mai kēlā me kēia electrode (610-10,000 Hz) e unuhi i ka hana multi-unit (MUA). Ua hoʻonohonoho pono ʻia nā pae hoʻoulu no kēlā me kēia. ʻO ka electrode (e nā mea kākau like i hoʻopōkole ʻia i nā kūlana i hōʻike ʻia a i ʻole i hōʻike ʻia) e koho i ka hiki ke hana nui loa mai ka hōʻailona. Ua hōʻike ka nānā ʻana ma ka pūnaewele a me ka pūnaewele ʻole o nā ʻano nalu ua hōʻiliʻili ʻia ka MUA ma ʻaneʻi i nā hiki ke hana i hana ʻia e 3 a 6 mau neurons kokoke i nā electrodes. I ka hoʻomaka ʻana o kēlā me kēia hoʻokolohua, ua hoʻonohonoho mākou i ke kūlana o ka pūʻulu electrode i hiki i ʻelua lālani o ʻewalu mau electrodes ke laʻana i nā neurons, mai nā pane alapine haʻahaʻa a kiʻekiʻe i ka wā i hana ʻia ai ma ke kuhikuhi rostral.
Ua hoʻokumu ʻia nā mea hoʻoulu leo ​​leo ma Matlab, i hoʻouna ʻia i kahi ʻōnaehana hoʻouna leo e pili ana i ka RP2.1 (TDT) a hoʻouna ʻia i kahi mea hoʻolele leo Fostex (FE87E). Ua kau ʻia ka mea hoʻolele leo he 2 cm mai ka pepeiao ʻākau o ka ʻiole, ma kahi mamao i hana ai ka mea hoʻolele leo i kahi alapine pālahalaha (± 3 dB) ma waena o 140 Hz a me 36 kHz. Ua hana ʻia ka hoʻoponopono ʻana o ka mea hoʻolele leo me ka hoʻohana ʻana i ka walaʻau a me nā leo maʻemaʻe i hoʻopaʻa ʻia me kahi microphone Bruel lāua ʻo Kjaer 4133 i hoʻopili ʻia me kahi preamplifier B&K 2169 a me ka mea hoʻopaʻa leo kikohoʻe Marantz PMD671. Ua hoʻoholo ʻia ke kahua Spectral Time Receptive Field (STRF) me ka hoʻohana ʻana i 97 mau alapine leo gamma, e uhi ana i 8 (0.14–36 kHz) octaves, i hōʻike ʻia ma ke ʻano maʻamau ma 75 dB SPL ma 4.15 Hz. Hoʻoholo ʻia ka Frequency Response Area (FRA) me ka hoʻohana ʻana i ka hoʻonohonoho like o nā leo a hōʻike ʻia ma ke ʻano maʻamau ma 2 Hz mai 75 a 5 dB SPL. ʻO kēlā me kēia hōʻike ʻia ke alapine (frequency) i ʻewalu manawa ma kēlā me kēia ikaika.
Ua loiloi ʻia hoʻi nā pane i nā stimuli kūlohelohe. Ma nā haʻawina i hala, ua ʻike mākou ʻaʻole i hoʻopuka pinepine nā leo leo iole i nā pane ikaika ma ACx, me ka nānā ʻole i ka neuronal optimal frequency (BF), ʻoiai ʻo xenograft-specific (e.g., songbird a guinea pig vocalizations) maʻamau ka palapala leo holoʻokoʻa. No laila, ua hoʻāʻo mākou i nā pane cortical i nā leo leo i nā puaʻa guinea (ua pili ka whistle i hoʻohana ʻia ma 36 i 1 s o nā stimuli, i hōʻike ʻia he 25 mau manawa).

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