Sirkadiyalik ritm - Circadian rhythm

Sirkadiyalik ritm
Biologik soat inson.svg
Odam sirkadiyanining (24 soatlik) biologik soatining ba'zi xususiyatlari
Talaffuz
ChastotaniHar 24 soatda bir marta

A sirkadiyalik ritm uyqudan uyg'onish tsiklini tartibga soluvchi va Yerning har bir aylanishida taxminan har 24 soatda takrorlanadigan tabiiy, ichki jarayondir.[1] An ko'rsatadigan har qanday biologik jarayonga murojaat qilishi mumkin endogen, qiziquvchan tebranish taxminan 24 soat. Ushbu 24 soatlik ritmlarni a boshqaradi sirkadiyalik soat va ular keng kuzatilgan o'simliklar, hayvonlar, qo'ziqorinlar va siyanobakteriyalar.[2]

Atama sirkadiyalik dan keladi Lotin taxminan, "atrofida" (yoki "taxminan") ma'nosini anglatadi va diēm, "kun" ma'nosini anglatadi. Biologik vaqtinchalik ritmlarni, masalan kundalik, to'lqin, haftalik, mavsumiy va yillik ritmlar deyiladi xronobiologiya. 24 soatlik tebranishlar bo'lgan jarayonlar odatda ko'proq chaqiriladi kunlik ritmlar; qat'iyan aytganda, endogen tabiati tasdiqlanmasa, ularni sirkadiyalik ritm deb atash kerak emas.[3]

Sirkadiyalik ritmlar endogen ("ichki", o'z-o'zini qo'llab-quvvatlaydigan) bo'lsa-da, ular tashqi muhit yordamida mahalliy muhitga o'rnatiladi (qo'shiladi) zeitgebers (nemis tilidan "vaqt beruvchi"), bu yorug'lik, harorat va oksidlanish-qaytarilish tsikllar. Tibbiyot fanida odamlarda g'ayritabiiy sirkadiyalik ritm ma'lum sirkadiyalik ritm buzilishi.[4]

2017 yilda Fiziologiya yoki tibbiyot bo'yicha Nobel mukofoti bilan taqdirlandi Jeffri C. Xoll, Maykl Rosbash va Maykl V. Yang "sirkadiyalik ritmni boshqaruvchi molekulyar mexanizmlarning kashfiyotlari uchun" mevali chivinlar.[5]

Tarix

Sharqiy va tub amerikalik madaniyatlarda "tabiiy tana aylanishi" haqida bir necha bor eslatib o'tilgan bo'lsa-da, sirkadiy jarayonining dastlabki G'arbdagi qaydlari miloddan avvalgi IV asrga to'g'ri keladi. Androsthenes, ostida xizmat ko'rsatadigan kema kapitani Buyuk Aleksandr tasvirlangan kunduzgi ning barg harakatlari tamarind daraxt.[6] Odamlarda sirkadiy yoki kunduzgi jarayonning kuzatilishi eslatib o'tilgan Xitoy tibbiy matnlari taxminan 13-asrga tegishli, shu jumladan Tush va yarim tunda qo'llanma va Kunduzgi tsikl, oy kuni va yil fasli bo'yicha aku nuqtalarini tanlashda yordam beradigan mnemonik qofiya..[7]

1729 yilda frantsuz olimi Jan-Jak d'Ortuz de Mairan endogen soatni kundalik ogohlantirishlarga ta'siridan ajratish uchun mo'ljallangan birinchi tajribani o'tkazdi. Uning ta'kidlashicha, o'simlik barglari harakatida 24 soatlik naqshlar Mimoza pudica o'simliklar doimiy zulmatda saqlanganda ham davom etdi.[8][9]

1896 yilda Patrik va Gilbert uzoq vaqt davomida uyqusiz qolish vaqtida uyquchanlik ko'payib, taxminan 24 soat davom etishi bilan kamayishini kuzatdilar.[10] 1918 yilda, J.S. Szimanski yorug'lik va harorat o'zgarishi kabi tashqi belgilar bo'lmasa, hayvonlar 24 soatlik faoliyat tartibini saqlab turishga qodir ekanligini ko'rsatdi.[11]

20-asrning boshlarida asalarilarning ritmik ovqatlanish davrida sirkadiyalik ritmlar kuzatilgan. Ogyust Forel, Ingeborg Beling, va Oskar Vahl ushbu ritmning ichki soatga bog'liqligini aniqlash uchun ko'plab tajribalar o'tkazdi.[12] Sirkadiyalik ritmning mavjudligi mustaqil ravishda kashf etilgan mevali chivin 1935 yilda ikkita nemis zoologlari tomonidan, Xans Kalmus va Ervin Bünning.[13][14]

1954 yilda muhim tajriba tomonidan xabar berilgan Kolin Pittendrigh buni namoyish etdi portlash (pupaning kattalarga aylanish jarayoni) yilda Drosophila pseudoobscura sirkadiyalik xatti-harakatlar edi. Uning ta'kidlashicha, ekloslanish ritmida harorat o'ta muhim rol o'ynagan bo'lsa-da, tutilish davri kechiktirilgan, ammo harorat pasayganda to'xtamagan.[15][14]

Atama sirkadiyalik tomonidan yaratilgan Frants Xelberg 1959 yilda.[16] Halbergning asl ta'rifiga ko'ra:

"Sirkadiyan" atamasi kelib chiqqan taxminan (haqida) va o'ladi (kun); bu ma'lum fiziologik davrlar, agar aynan shu uzunlik bo'lmasa, 24 soatga yaqin ekanligini anglatishi mumkin. Bu erda "tsirkadian" barcha "24 soatlik" ritmlarga, ularning davrlari alohida yoki o'rtacha bo'ladimi-yo'qligiga qaramay, 24 soatdan, uzoqroq yoki qisqaroq, bir necha daqiqa yoki soatga farq qilishi mumkin.[17][18]

1977 yilda Xalqaro nomenklatura qo'mitasi Xalqaro xronobiologiya jamiyati rasmiy ravishda ta'rifni qabul qildi:

Sirkadiyan: 24 ± 4 soat ichida 1 tsikl chastotali biologik o'zgarishlarga yoki ritmlarga taalluqli; taxminan (taxminan, taxminan) va o'ladi (kun yoki 24 soat). Izoh: atama 24 soatlik tsiklning ritmini tavsiflaydi, ular chastotada sinxronlashtiriladimi (qabul qilinadi) yoki mahalliy vaqt shkalasi bilan sinxronlashtiriladimi yoki erkin harakat qiladimi, davri 24 soatdan bir oz farqli o'laroq.[19]

Ron Konopka va Seymur shunga o'xshash soat mutatsiyasini aniqladi Drosophila 1971 yilda gen nomini berish "davr " (per) gen, xulq-atvor ritmikligining birinchi kashf etilgan genetik determinanti.[20] per gen 1984 yilda ikkita tadqiqotchilar guruhi tomonidan ajratilgan. Konopka, Jeffri Xoll, Maykl Roshbash va ularning jamoasi buni ko'rsatdi per lokus sirkadiyalik ritmning markazidir va bu yo'qotish per sirkadiyalik faoliyatni to'xtatadi.[21][22] Shu bilan birga, Maykl V. Yangning jamoasi shunga o'xshash ta'sirlarni qayd etdi perva gen X xromosomasidagi 7,1 kilobaza (kb) oralig'ini qamrab oladi va 4,5 kbli poli (A) + RNKni kodlaydi.[23][24] Ular asosiy genlarni va neyronlarni kashf etishga kirishdilar Drosophila sirkadiy tizim, buning uchun Xoll, Rosbash va Young olganlar Fiziologiya yoki tibbiyot bo'yicha Nobel mukofoti 2017 yil.[5]

Jozef Takaxashi birinchi sutemizuvchilar sirkadiyalik soat mutatsiyasini topdi (soat Δ19) 1994 yilda sichqonlar yordamida.[25][26] Biroq, so'nggi tadqiqotlar shuni ko'rsatadiki, soat xulq-atvor fenotipiga olib kelmaydi (hayvonlar hanuzgacha oddiy tsirkadiyalik ritmlarga ega), bu uning ritm hosil qilishdagi ahamiyatini shubha ostiga qo'yadi.[27][28]

Birinchi inson soati mutatsiyasini Yuta shtatining kengaytirilgan oilasida Kris Jons aniqlagan va genetik jihatdan Ying-Xuy Fu va Lui Ptakeklar tomonidan tavsiflangan. Ta'sirga uchragan shaxslar 4 soatlik yuqori uyqu va boshqa ritmlarga ega bo'lgan o'ta "ertalab laklar" dir. Familial Advanced uyqu fazasining ushbu shakli insonning PER2 oqsilidagi S662➔G aminokislota o'zgarishi natijasida yuzaga keladi.[29][30]

Mezon

Sirkadiy deb atash uchun biologik ritm quyidagi uchta umumiy mezonga javob berishi kerak:[31]

  1. Ritm endogen erkin harakatlanish davriga ega, u taxminan 24 soat davom etadi. Ritm doimiy sharoitda (ya'ni doimiy zulmatda) davom etadi va taxminan 24 soat davom etadi. Ritmning doimiy sharoitdagi davri erkin yugurish davri deb ataladi va yunoncha τ (tau) harfi bilan belgilanadi. Ushbu mezonning asoslari sirkadiyalik ritmlarni oddiy javoblardan kundalik tashqi signallarga ajratishdir. Ritmni aytish mumkin emas endogen agar u sinovdan o'tkazilmasa va tashqi davriy kiritilmasdan davom etsa. Kunduzgi hayvonlarda (kunduzgi soatlarda faol) umuman τ 24 soatdan biroz kattaroq, tungi hayvonlarda (tunda faol) umuman 24 24 soatdan qisqa.
  2. Ritmlar o'ziga jalb qiladi. Ritmni tashqi ta'sir (masalan, yorug'lik va issiqlik) ta'sirida tiklash mumkin, bu jarayon deyiladi qiziqish. Ritmni jalb qilish uchun ishlatiladigan tashqi stimulga deyiladi Zeitgeber yoki "vaqt beruvchi". Sayohat bo'ylab vaqt zonalari inson biologik soatining mahalliy vaqtga moslash qobiliyatini aks ettiradi; bir kishi odatda boshdan kechiradi vaqt mintaqasi o'zgarishi xastaligi oldin ularning sirkadiyalik soatlari mahalliy vaqt bilan sinxronlashtirildi.
  3. Ritmlar haroratni qoplashni namoyish etadi. Boshqacha qilib aytganda, ular fiziologik harorat oralig'ida sirkad davriyligini saqlab turadilar. Ko'pgina organizmlar keng haroratda yashaydilar va issiqlik energiyasidagi farqlar ta'sir qiladi kinetika ularning hujayralaridagi barcha molekulyar jarayonlarning. Vaqtni hisobga olish uchun organizmning sirkadiy soati harorat o'zgarishi deb nomlanuvchi kinetikaga qaramay, taxminan 24 soatlik davriylikni saqlab turishi kerak. The Q10 harorat koeffitsienti bu kompensatsiya ta'sirining o'lchovidir. Agar harorat oshishi bilan Q10 koeffitsienti taxminan 1 bo'lib qolsa, ritm harorat bilan qoplanadi deb hisoblanadi.

Kelib chiqishi

Sirkadiyalik ritmlar organizmlarga atrof-muhitning aniq va muntazam o'zgarishini kutish va tayyorlashga imkon beradi. Shunday qilib, ular organizmlarga atrof-muhit resurslaridan (masalan, yorug'lik va oziq-ovqat) bu kabi mavjudlikni taxmin qila olmaydigan narsalardan yaxshiroq foydalanishga imkon beradi. Shuning uchun sirkadiyalik ritmlar evolyutsiya nuqtai nazaridan organizmlarni tanlab afzalliklarga olib keladi degan fikrlar mavjud. Biroq, ritmiklik tartibga solish va muvofiqlashtirishda muhim ahamiyatga ega ko'rinadi ichki metabolik jarayonlar, bilan muvofiqlashtirganidek atrof-muhit.[32] Bu doimiy laboratoriya sharoitida bir necha yuz avloddan keyin mevali chivinlarda sirkadiyalik ritmlarning saqlanib turishi (merosxo'rligi) tomonidan taklif qilingan,[33] yovvoyi tabiatda doimiy zulmatda bo'lgan jonzotlarda va fiziologik emas, balki xulq-atvorni eksperimental tarzda yo'q qilish orqali bedana.[34][35]

Sirkadiyalik ritmlarni rivojlanishiga undagan narsa sirli savol edi. Oldingi gipotezalarda ta'kidlanishicha, fotosensitiv oqsillar va tsirkadiyan ritmlari dastlabki hujayralarda paydo bo'lishi mumkin, bu esa replikatsiya qilinadigan DNKni yuqori darajadagi zararli moddalardan himoya qilishdir. ultrabinafsha kunduzi nurlanish. Natijada, replikatsiya zulmatga tushdi. Biroq, buning dalillari kam, chunki tsirkad ritmiga ega bo'lgan eng sodda organizmlar - siyanobakteriyalar buning aksini qiladi - ular kunduzi ko'proq bo'linadi.[36] So'nggi tadqiqotlar o'rniga oksidlanish-qaytarilish oqsillarining sirkadiyali osilatorlar bilan birgalikda evolyutsiyasi hayotning uchta sohasidagi quyidagi muhim ahamiyatga ega. Ajoyib Oksidlanish hodisasi taxminan 2,3 milliard yil oldin.[2][4] Hozirgi ko'rinish shundan iboratki, atrof-muhitdagi kislorod darajasidagi va ishlab chiqarishdagi sirkadiyalik o'zgarishlar reaktiv kislorod turlari (ROS) kunduzgi yorug'lik mavjud bo'lganda, ehtimol kundalik ravishda oksidlanish-qaytarilish reaktsiyalarini oldini olish uchun sirkadiyalik ritmlarni rivojlantirish zarurati tug'dirgan.

Eng sodda ma'lum sirkadiyalik soatlar bor bakterial sirkadiyalik ritmlar, prokaryot tomonidan misol keltirilgan siyanobakteriyalar. Yaqinda o'tkazilgan tadqiqotlar shuni ko'rsatdiki, sirkadiyalik soat Synechococcus elongatus qayta tiklanishi mumkin in vitro faqat uchta oqsil bilan (KaiA, KaiB, KaiC )[37] ularning markaziy osilatorining Ushbu soat qo'shilganidan keyin bir necha kun davomida 22 soatlik ritmni ushlab turishi ko'rsatilgan ATP. Ning oldingi izohlari prokaryotik sirkadiyalik timekeeper DNKning transkripsiyasi / tarjimasi bilan qayta aloqa mexanizmiga bog'liq edi.[iqtibos kerak ]

Inson gomologidagi nuqson Drosophila "davr "FASPS uyqu buzilishining sababi sifatida gen aniqlandi (Oilaviy rivojlangan uyqu fazasi sindromi ), evolyutsiya orqali molekulyar sirkadiyalik soatning saqlanib qolgan xususiyatini ta'kidlaydi. Hozirgi kunda biologik soatning ko'plab boshqa genetik tarkibiy qismlari ma'lum. Ularning o'zaro ta'siri natijasida gen hujayralarining bir-biriga bog'langan teskari aloqasi mavjud bo'lib, natijada tana hujayralari kunning ma'lum bir vaqti sifatida talqin qiladi.[38]

Hozir ma'lumki, molekulyar sirkadiyalik soat bitta hujayra ichida ishlashi mumkin; ya'ni hujayra-avtonomdir.[39] Bu tomonidan ko'rsatilgan Gen bloki ajratilgan mollyusk bazal retinal neyronlarda (BRN).[40] Shu bilan birga, turli xil hujayralar bir-biri bilan aloqa qilishlari mumkin, natijada elektr signalizatsiyasi sinxronlashtiriladi. Ular bilan interfeys bo'lishi mumkin ichki sekretsiya bezlari gormonlarning vaqti-vaqti bilan chiqarilishiga olib keladigan miyaning. Ushbu gormonlar retseptorlari tanadan uzoqroq masofada joylashgan bo'lishi va turli organlarning periferik soatlarini sinxronlashtirishi mumkin. Shunday qilib, kunning vaqti haqidagi ma'lumot ko'zlar miyadagi soatga boradi va shu orqali tananing qolgan qismidagi soatlar sinxronlashtirilishi mumkin. Masalan, uxlash / uyg'onish, tana harorati, chanqoqlik va ishtaha vaqti biologik soat tomonidan muvofiqlashtirilib boshqariladi.[41][42]

Hayvonlarda ahamiyati

Sirkadiyalik ritmiklik hayvonlarning, shu jumladan odamlarning uxlash va ovqatlanish tartiblarida mavjud. Tana haroratining aniq namunalari ham mavjud, miya to'lqini faoliyat, gormon ishlab chiqarish, hujayralarni qayta tiklash va boshqa biologik faoliyat. Bunga qo'chimcha, fotoperiodizm, organizmlarning fiziologik reaktsiyasi kun yoki tun davomiyligi, o'simliklar va hayvonlar uchun juda muhimdir va sirkadiya tizimi kun uzunligini o'lchash va talqin qilishda muhim rol o'ynaydi. Ob-havo sharoitining mavsumiy davrlarini, oziq-ovqat mavjudligini yoki yirtqich hayvonlarning faolligini o'z vaqtida bashorat qilish ko'plab turlarning yashashi uchun juda muhimdir. Faqatgina parametr bo'lmasa-da, fotoperiodning o'zgaruvchan uzunligi ("kun bo'yi") fiziologiya va xulq-atvorning mavsumiy vaqti uchun, eng muhimi, migratsiya, qish uyqusi va ko'payish vaqtlari uchun eng taxminiy ekologik belgidir.[43]

Sirkadiy buzilishining ta'siri

Sichqonlardagi mutatsiyalar yoki soat genining yo'q qilinishi uyali / metabolik hodisalarning to'g'ri vaqtini ta'minlash uchun tana soatlarining muhimligini ko'rsatdi; mutant sichqonlar giperfagik va semirib ketgan va glyukoza metabolizmini o'zgartirgan.[44] Sichqonlarda Rev-ErbA alfa soat geni dietadan kelib chiqqan semirishni osonlashtiradi va diabetga moyil bo'lgan glyukoza va lipidlardan foydalanish o'rtasidagi muvozanatni o'zgartiradi.[45] Biroq, odamlarda soat geni polimorfizmlari va metabolik sindromni rivojlanishiga moyilligi o'rtasida kuchli bog'liqlik mavjudmi yoki yo'qligi aniq emas.[46][47]

Yorug'lik-qorong'i tsiklning ta'siri

Ritm qorong'ulik va tsikl tsikli bilan bog'liq. To'liq zulmatda bo'lgan hayvonlar, shu jumladan odamlar, uzoq vaqt davomida a bilan ishlaydi erkin ishlaydigan ritm. Ularning uyqu tsikli har bir "kun" oldinga yoki oldinga suriladi, bu ularning "kuni" ga, ularning endogen 24 soatdan qisqa yoki uzoqroq. Har kuni ritmlarni qayta tiklaydigan atrof-muhit signallari zeitgeberlar deb nomlanadi (nemis tilidan "vaqt ajratuvchilar").[48] Umuman ko'r er osti sutemizuvchilar, masalan. ko'r mol kalamush Spalaks sp., tashqi stimul yo'qligida o'zlarining endogen soatlarini saqlab turishga qodir. Ularda tasvir hosil qiluvchi ko'zlar etishmasa ham, ularning fotoreseptorlari (yorug'likni aniqlaydigan) hanuzgacha ishlaydi; ular vaqti-vaqti bilan ham sirt qilishadi.[sahifa kerak ][49]

Odatda, bir yoki ikkita konsolidatsiyalangan uyqu epizodiga ega bo'lgan erkin harakatlanuvchi organizmlar tashqi signallardan himoyalangan muhitda bo'lishadi, ammo ritm tabiatdagi 24 soatlik qorong'ulik tsikliga bog'liq emas. Bunday holda, uyquni uyg'otish ritmi boshqa sirkadiyaliklar bilan fazadan chiqib ketishi mumkin ultradian metabolik, gormonal, CNS elektr yoki neyrotransmitter ritmlari kabi ritmlar.[50]

So'nggi tadqiqotlar dizayniga ta'sir ko'rsatdi kosmik kemalar atrof-muhit, chunki yorug'lik-qorong'i tsiklni taqlid qiluvchi tizimlar astronavtlar uchun juda foydali ekanligi aniqlandi.[51]

Arktika hayvonlari

Norvegiyalik tadqiqotchilar Tromsø universiteti ba'zi ekanligini ko'rsatdi Arktika hayvonlari (ptarmigan, kiyik ) sirkadiyalik ritmlarni faqat kunning quyoshi va quyosh botishi bo'lgan qismlarida ko'rsating. Kiyiklarning bir tadqiqotida hayvonlar 70 daraja shimol kuzda, qishda va bahorda sirkadiyalik ritmlarni namoyish etdi, ammo yozda emas. Bug'u yoqilgan Svalbard da Shimoliy 78 daraja bunday ritmlarni faqat kuzda va bahorda namoyish etdi. Tadqiqotchilar boshqa Arktika hayvonlari ham yozning doimiy yorug'ida va qishda doimiy qorong'ida sirkadiyalik ritmlarni namoyish etmasligi mumkin deb taxmin qilishmoqda.[52]

Shimoliy Alyaskada 2006 yilda o'tkazilgan tadqiqotlar shuni aniqladiki, kunlik hayot tuproqli sincaplar va tungi kirpiklar 82 kun va tun davomida quyosh nurlari bilan sirkadiyalik ritmlarni qat'iyan saqlab turing. Tadqiqotchilarning fikriga ko'ra, bu ikkita kemiruvchi quyosh va ufq orasidagi aniq masofa kuniga bir marta eng qisqa va shuning uchun ularni jalb qilish (sozlash) uchun etarli signalga ega.[53]

Kelebek va kuya

Ning kuzgi migratsiyasi navigatsiyasi Sharqiy Shimoliy Amerika monarxi kapalagi (Danaus pleksippus) Meksikaning markazida o'zlarining qishlash joylarida antennalaridagi sirkadiyalik soatga bog'liq bo'lgan vaqtni qoplaydigan quyosh kompasidan foydalanadilar.[54][55] Shuningdek, sirkadiyalik ritm ma'lum bir kuya turlarida juftlashish xatti-harakatlarini boshqarishi ham ma'lum Spodoptera littoralis, bu erda urg'ochilar aniq ishlab chiqaradilar feromon tunda juftlashishni boshlash uchun erkak sirkadiyalik ritmni o'ziga jalb qiladi va tiklaydi.[56]

O'simliklarda

Kechayu kunduz uxlab yotgan daraxt

O'simliklarning tsirkadiyan ritmlari o'simlikka qaysi fasl va qachon gullashini changlatuvchilarni jalb qilishning eng yaxshi imkoniyati to'g'risida aytib beradi. Ritmlarni ko'rsatadigan xatti-harakatlarga barglar harakati, o'sishi, unib chiqishi, stomatal / gaz almashinuvi, fermentlar faolligi, fotosintez faolligi va parfyum emissiyasi va boshqalar kiradi.[57] Sirkadiyalik ritmlar o'simlik atrofdagi muhitning yorug'lik aylanishi bilan sinxronlash uchun majburlashi natijasida paydo bo'ladi. Ushbu ritmlar ichki hosil bo'ladi va o'zini o'zi ta'minlaydi va atrof-muhit harorati bo'yicha nisbatan doimiydir. Muhim xususiyatlarga ikkita o'zaro ta'sir qiluvchi transkripsiya-tarjima teskari aloqa davri kiradi: protein-oqsillarning o'zaro ta'sirini osonlashtiradigan PAS domenlarini o'z ichiga olgan oqsillar; va soatni har xil yorug'lik sharoitlariga moslashtiradigan bir nechta fotoreseptorlar. Atrof muhitdagi o'zgarishlarni kutish o'simlikning fiziologik holatini mos ravishda o'zgartirishga, adaptiv ustunlik berishga imkon beradi.[58] O'simliklarning tsirkadiyan ritmlarini yaxshiroq anglash qishloq xo'jaligida, masalan, dehqonlarga hosilni yig'ib-terib olishda yordam berish va ob-havo tufayli katta yo'qotishlarga qarshi kurashishda yordam beradi.

Nur - bu o'simliklar o'zlarining ichki soatlarini atrof-muhit bilan sinxronlashtiradigan va turli xil fotoreseptorlar tomonidan seziladigan signaldir. Qizil va ko'k yorug'lik bir nechta fitoxromlar orqali va kriptoxromlar. Bitta fitoxrom, phyA, qorong'ida o'sgan ko'chatlarning asosiy fitoxromidir, ammo nurda tezda parchalanib, Cry1 hosil qiladi. B-E fitoxromlari nurda o'stirilgan ko'chatlarda asosiy fitoxrom bo'lgan fit bilan barqarorroq bo'ladi. Kriptoxrom (qichqiriq) geni ham sirkadiyalik soatning nurga sezgir tarkibiy qismidir va u fotoreseptor sifatida ham, soatning endogen yurak stimulyatori mexanizmining bir qismi sifatida ham ishtirok etadi deb o'ylashadi. 1-2 kriptoxromlari (ko'k-UVA bilan bog'liq) butun yorug'lik sharoitida soat uzunligini saqlab turishga yordam beradi.[57][58]

Markaziy osilator o'zini o'zi ushlab turuvchi ritmni hosil qiladi va uni kunning turli vaqtlarida faol bo'lgan ikkita o'zaro ta'sir qaytaruvchi ko'chadan boshqaradi. Ertalabki tsikl CCA1 (Circadian va Clock-Associated 1) va LHY (kech cho'zilgan gipokotil) dan iborat bo'lib, ular atrofdagi sirkadiyalik ritmlarni tartibga soluvchi MYB transkripsiyasi omillarini kodlaydi. Arabidopsis, shuningdek PRR 7 va 9 (Pseudo-Response Regulators.) Kechki tsikl GI (Gigantea) va ELF4 dan iborat bo'lib, ikkalasi ham gullash vaqtining genlarini boshqarishda ishtirok etadi.[59][60] CCA1 va LHY haddan tashqari ta'sirlanganda (doimiy yorug'lik yoki qorong'i sharoitda) o'simliklar aritmik holga keladi va mRNK signallari kamayadi va salbiy teskari aloqa aylanishiga yordam beradi. CCA1 va LHY ning gen ekspresiyasi tebranadi va erta tongda eng yuqori darajaga etadi TOC1 geni erta kechqurun ifoda tebranadi va eng yuqori nuqtaga etadi. Ilgari ushbu uchta gen salbiy eksklyuziv tsiklni modellashtiradi, unda haddan tashqari ifoda etilgan CCA1 va LHY TOC1ni repressiya qiladi va haddan tashqari ifoda etilgan TOC1 CCA1 va LHY ning ijobiy regulyatori hisoblanadi.[58] 2012 yilda Endryu Millar va boshqalar tomonidan TOC1 aslida CCA1, LHY va PRR7 va 9 ning nafaqat ertalabki tsiklda, balki GI va ELF4 da ham kechqurun repressor bo'lib xizmat qilishi ko'rsatilgan. Ushbu topilma va keyingi hisoblash modellashtirish TOC1 geni funktsiyalar va o'zaro ta'sirlar o'simlik tsirkadiy soatining uch baravar salbiy komponent sifatida qayta tuzilishini taklif qiladi repressilator sutemizuvchilarda soatni tavsiflovchi ijobiy / manfiy elementlarning teskari aloqasi o'rniga model.[61]

2018 yilda tadqiqotchilar PRR5 va TOC1 hnRNA tug'ma transkriptlarining ekspressioni A.thaliana-da ritmik ravishda qayta ishlangan mRNA transkriptlari bilan bir xil tebranish sxemasiga mos kelishini aniqladilar. LNKs PRR5 va TOC1 ning 5 mintaqasi bilan bog'lanib, RNAP II va boshqa transkripsiya omillari bilan o'zaro ta'sir qiladi. . Bundan tashqari, RVE8-LNKlarning o'zaro ta'siri, ruxsat etilgan histon-metilasyon naqshini (H3K4me3) o'zgartirishga imkon beradi va giston modifikatsiyasining o'zi soat geni ekspresiyasining tebranishiga parallel.[62]

Ilgari o'simlikning tsirkadiy ritmini tashqi muhitning qorong'i va qorong'u davrlariga mos kelishi o'simlikka ijobiy ta'sir ko'rsatishi mumkinligi aniqlangan edi.[63] Tadqiqotchilar uch xil nav bo'yicha tajribalar o'tkazib, shunday xulosaga kelishdi Arabidopsis talianasi. Ushbu navlardan biri odatiy 24 soatlik tsirkadiyalik tsiklga ega edi.[63] Qolgan ikkita nav mutatsiyaga uchragan, ulardan biri sirkadiyalik tsikl 27 soatdan ortiq, bittasi oddiy sirkadiyalik tsikl tsikli 20 soatdan iborat.[63]

24 soatlik tsirkad tsikli bilan ishlaydigan Arabidopsis uch xil muhitda o'stirildi.[63] Ushbu muhitlarning birida 20 soatlik yorug'lik va qorong'i tsikl (10 soat yorug'lik va 10 soat qorong'i), ikkinchisida 24 soat yorug'lik va qorong'i tsikl (12 soat yorug'lik va 12 soat qorong'i) va yakuniy muhit 28 soatlik qorong'i va qorong'i tsiklga ega edi (14 soat yorug'lik va 14 soat qorong'i).[63] Ikkita mutatsiyaga uchragan o'simliklar 20 soatlik yorug'lik va qorong'u tsiklga ega bo'lgan muhitda ham, 28 soatlik yorug'lik va qorong'i tsiklga ega bo'lgan muhitda o'stirildi.[63] 24 soatlik yorug'lik va qorong'i tsiklga ega bo'lgan muhitda 24 soatlik tsirkadiy ritm tsikli bilan arabidopsisning xilma-xilligi eng yaxshi o'sganligi aniqlandi.[63] Umuman olganda, barcha navlari aniqlandi Arabidopsis talianasi ko'proq xlorofill darajalariga ega va yorug'lik va qorong'u tsikllar o'zlarining tsirkadiy ritmiga mos keladigan muhitda o'sishni oshirgan.[63]

Tadqiqotchilar buning sababi Arabidopsisning sirkadiyalik ritmini uning atrof-muhitiga mos kelishi o'simlikning tong va shom tushishiga yaxshiroq tayyorlanishiga va shu bilan uning jarayonlarini yaxshiroq sinxronlashtirishga imkon berishi mumkin deb taxmin qilishdi.[63] Ushbu tadqiqotda xlorofillni boshqarishda yordam beradigan genlar tong otgandan bir necha soat o'tgach eng yuqori darajaga ko'tarilganligi aniqlandi.[63] Bu metabolik shafaq deb nomlanuvchi taklif qilingan hodisaga mos keladi.[64]

Metabolik tong gipotezasiga ko'ra, fotosintez natijasida hosil bo'lgan qandlar tsirkad ritmini va ba'zi fotosintez va metabolizm yo'llarini boshqarishda yordam beradi.[64][65] Quyosh ko'tarilishi bilan ko'proq yorug'lik paydo bo'ladi, bu odatda ko'proq fotosintez sodir bo'lishiga imkon beradi.[64] Fotosintez natijasida hosil bo'lgan shakar PRR7ni siqib chiqaradi.[66] Ushbu PRR7 repressiyasi keyinchalik CCA1 ekspressionining kuchayishiga olib keladi.[66] Boshqa tomondan, fotosentetik shakar darajasining pasayishi PRR7 ekspressionini oshiradi va CCA1 ekspressionini pasaytiradi.[64] CCA1 va PRR7 o'rtasidagi ushbu teskari aloqa metabolik tongni keltirib chiqaradigan narsa.[64][67]

Yilda Drosophila

Sutemizuvchilarning asosiy markazlari va Drosophila miya (A) va sirkadiy tizim Drosophila (B).

Sirkadiyalik ritm va yorug'likni sezishning molekulyar mexanizmi eng yaxshi tushuniladi Drosophila. Soat genlari topilgan Drosophilava ular soat neyronlari bilan birgalikda harakat qilishadi. Ikkita noyob ritm mavjud, ulardan biri lyuklash jarayonida (deyiladi) portlash ) kukladan, ikkinchisi esa juftlash paytida.[68] Soat neyronlari markaziy miyada alohida klasterlarda joylashgan. Eng yaxshi tushunilgan soat neyronlari bu katta va kichik lateral ventral neyronlar (l-LNvs va s-LNvs). optik lob. Ushbu neyronlar pigmentlarning tarqaladigan omilini (PDF) ishlab chiqaradi, bu neyropeptid bo'lib, u har xil soat neyronlari o'rtasida sirkadiyalik neyromodulyator vazifasini bajaradi.[69]

Soat genlari va oqsillarning molekulyar o'zaro ta'siri Drosophila sirkadiyalik ritm.

Drosophila sirkadiyalik ritm transkripsiya-tarjima teskari aloqasi orqali amalga oshiriladi. Asosiy soat mexanizmi o'zaro bog'liq ikkita teskari aloqa tsiklidan iborat, ya'ni PER / TIM tsikli va CLK / CYC tsikli.[70] CLK / CYC tsikli kun davomida sodir bo'ladi va transkripsiyasini boshlaydi per va tim genlar. Ammo ularning oqsillari shom tushguncha past bo'lib qoladi, chunki kunduzi ham faollashadi ikkilamchi vaqt (dbt) gen. DBT oqsili monomerik PER oqsillarining fosforlanishiga va aylanishiga olib keladi.[71][72] TIM, shuningdek, quyosh botguncha shaggy tomonidan fosforillanadi. Quyosh botganidan keyin DBT yo'qoladi, shuning uchun PER molekulalari TIM bilan barqaror bog'lanadi. PER / TIM dimer tunda bir necha marta yadroga kiradi va CLK / CYC dimerlari bilan bog'lanadi. Bound PER CLK va CYC ning transkripsiya faolligini to'liq to'xtatadi.[73]

Erta tongda yorug'lik yig'lamoq geni va uning oqsili CRY TIM ning parchalanishiga olib keladi. Shunday qilib PER / TIM dimer ajralib chiqadi va bog'lanmagan PER beqaror bo'ladi. PER progressiv fosforillanish va oxir-oqibat degradatsiyaga uchraydi. PER va TIM yo'qligi faollashtirishga imkon beradi clk va tsikl genlar. Shunday qilib, keyingi sirkadiyalik tsiklni boshlash uchun soat tiklanadi.[74]

PER-TIM modeli

Ushbu oqsil modeli Drozofiladagi PER va TIM oqsillarining tebranishlari asosida ishlab chiqilgan.[75] Uning asosi PER modeliga asoslangan bo'lib, u erda per gen va uning oqsili biologik soatga qanday ta'sir qilishi tushuntirildi.[76] Model, per va tim genlarining transkripsiyasiga (salbiy teskari aloqani ta'minlash orqali) va ushbu ikki oqsilning ko'p fosforlanishiga ta'sir qiluvchi yadro PER-TIM kompleksini shakllantirishni o'z ichiga oladi. Ushbu ikkita oqsilning sirkadiyali tebranishlari, agar ular unga bog'liq bo'lmasa ham, qorong'u qorong'i tsikl bilan sinxronlashadi.[77][75] Ikkala PER va TIM oqsillari ham fosforillanadi va ular PER-TIM yadro kompleksini hosil qilgandan so'ng ular per va tim mRNA ekspressionini to'xtatish uchun yadro ichiga qaytadilar. Ushbu inhibisyon oqsilgacha davom etadi yoki mRNK parchalanmaydi.[75] Bu sodir bo'lganda, kompleks inhibisyonni chiqaradi. Bu erda TIM oqsilining parchalanishi yorug'lik bilan tezlashishi haqida ham aytib o'tish mumkin.[77]

Sutemizuvchilarda

Ning o'zgarishi eskinogramma yorug'lik va zulmatning sirkadiyalik ritmlarga ta'sirini va shu bilan bog'liq bo'lgan narsalarni tasvirlash fiziologiya va orqali xatti-harakatlar supraxiyazmatik yadro odamlarda

Birlamchi sirkadiyalik soat yilda sutemizuvchilar da joylashgan supraxiyazmatik yadro (yoki yadrolari) (SCN), alohida guruhlarning juftligi hujayralar joylashgan gipotalamus. SCNni yo'q qilish muntazam ravishda uyqudan uyg'onish ritmining yo'qligiga olib keladi. SCN yorug'lik haqida ma'lumotni ko'z orqali oladi. The retina ko'zda "klassik" mavjud fotoreseptorlar ("tayoqchalar "va"konuslar "), odatiy ko'rish uchun ishlatiladi. Ammo retinada ixtisoslashgan ham mavjud ganglion hujayralari to'g'ridan-to'g'ri fotosensitiv va to'g'ridan-to'g'ri SCN-ga loyihalashadi, bu erda ular ushbu asosiy sirkadiyalik soatni jalb qilishda (sinxronlashtirishda) yordam beradi.[78]

Ushbu hujayralar fotopigmentni o'z ichiga oladi melanopsin va ularning signallari the deb nomlangan yo'ldan boradi retinohipotalamik trakt, SCN ga olib boradi. Agar SCN dan hujayralar olib tashlansa va o'stirilsa, tashqi belgilar bo'lmasa, ular o'zlarining ritmini saqlab turadilar.[79]

SCN kecha va kunduz davomiyligi haqidagi ma'lumotlarni retinadan oladi, uni sharhlaydi va epifiz bezi, a kabi shakllangan mayda inshoot qarag'ay konusi va joylashgan epitalamus. Bunga javoban epifal gormonni chiqaradi melatonin.[80] Kechasi melatonin sekretsiyasi va kunduzi havo pasayadi va uning mavjudligi tun bo'yi haqida ma'lumot beradi.

Bir necha tadkikotlar shuni ko'rsatdiki, epifel melatonin sirkadiyalik faoliyat turlarini va boshqa jarayonlarni modulyatsiya qilish uchun SCN ritmliligi bilan oziqlanadi. Biroq, ushbu mulohazaning mohiyati va tizim darajasidagi ahamiyati noma'lum.[81]

Odamlarning sirkadiyalik ritmlari Yerning 24 soatiga nisbatan bir oz qisqaroq va uzoqroq muddatlarga ega bo'lishi mumkin. Garvard tadqiqotchilari inson sub'ektlarini hech bo'lmaganda 23,5 soatlik tsiklga va 24,65 soatlik tsiklga (ikkinchisi sayyoradagi tabiiy quyosh kecha-kunduz tsikliga) jalb qilish mumkinligini ko'rsatdilar. Mars ).[82]

Odamlar

Ko'zlar quyoshdan nur olganda epifizda melatonin ishlab chiqarilishi inhibe qilinadi va ishlab chiqarilgan gormonlar odamni bedor tutadi. Ko'zlarga yorug'lik tushmasa, epifizda melatonin hosil bo'lib, odam charchaydi.

Sirkadiyalik ritmlarni o'rganish bo'yicha dastlabki tadqiqotlar shuni ko'rsatdiki, ko'pchilik odamlar kunduzgi yorug'lik va vaqtni saqlash kabi tashqi ta'sirlardan ajratilganda 25 soatga yaqin kunni afzal ko'rishadi. Biroq, ushbu tadqiqot noto'g'ri edi, chunki u ishtirokchilarni sun'iy nurdan himoya qila olmadi. Mavzular (soat kabi) va kunduzgi yorug'likdan himoyalangan bo'lsa-da, tadqiqotchilar ichki elektr chiroqlarning fazani kechiktiradigan ta'siridan xabardor emas edilar.[83][shubhali ] Mavzularga uyg'onganda yorug'likni yoqishga va uxlashni xohlaganda uni o'chirishga ruxsat berildi. Kechqurun elektr nuri ularning sirkadiy fazasini kechiktirdi.[84] 1999 yilda o'tkazilgan yanada qat'iy tadqiqot Garvard universiteti insonning tabiiy ritmini 24 soat 11 daqiqaga yaqinroq deb taxmin qildi: ga juda yaqin quyosh kuni.[85] Ushbu tadqiqotga muvofiq, 2010 yildagi so'nggi tadqiqotlar bo'lib, unda erkaklarnikiga qaraganda (24.09 soat) ayollar uchun bir oz qisqaroq (24.09 soat) bo'lgan tsirkad davri bilan jinsiy farqlar aniqlandi.[86] Ushbu tadqiqotda ayollar erkaklarnikidan ko'ra erta uyg'onishga moyil edilar va erkaklarnikiga qaraganda ertalabki mashg'ulotlarga ko'proq ustunlik berishadi, ammo bu farqlarning asosiy biologik mexanizmlari noma'lum.[86]

Biologik markerlar va effektlar

Sutemizuvchilarning sirkadiyan ritmining vaqtini o'lchash uchun klassik faz belgilari:

Haroratni o'rganish uchun mavzular hushyor turishi kerak, ammo rektumdagi harorat doimiy ravishda olinib turganda, yaqin qorong'ida tinch va yarim egiluvchan bo'lishi kerak. O'zgarishlar odatdagidek juda yaxshi xronotiplar, kattalardagi odamlarning o'rtacha harorati odatdagi uyg'onish vaqtidan taxminan ikki soat oldin taxminan soat 5:00 da minimal darajaga etadi. Baehr va boshq.[89] yosh kattalarda kunlik tana harorati ertalabki turlar uchun soat 04:00 da (soat 4 da), ammo kechqurun turlari uchun soat 06:00 da (soat 6 da) sodir bo'lganligi aniqlandi. Ushbu minimal ko'rsatkich ertalabki turlar uchun taxminan sakkiz soatlik uyqu davrining o'rtalarida sodir bo'lgan, ammo kechqurun uyg'onishga yaqinroq bo'lgan.

Melatonin tizimda yo'q yoki kunduzi aniqlanmaydi. Uning xira nurda boshlanishi, xira nurli melatonin boshlanishi (DLMO), taxminan soat 21:00 da (21:00) qon yoki tupurik bilan o'lchash mumkin. Uning asosiy qismi metabolit shuningdek, ertalab siydik bilan o'lchanishi mumkin. Ikkala DLMO va qonda yoki tupurikda gormon mavjudligining o'rta nuqtasi (o'z vaqtida) sirkadiyalik belgilar sifatida ishlatilgan. Ammo, yangi tadqiqotlar shuni ko'rsatadiki, melatonin ofset ishonchli marker bo'lishi mumkin. Benlousif va boshq.[87] melatonin fazasi markerlari eng past haroratga qaraganda ancha barqaror va uxlash vaqti bilan ko'proq bog'liqligini aniqladi. Ularning fikriga ko'ra, uyquni qoplash va melatonin bilan qoplash uyqu boshlanishidan ko'ra faza markerlari bilan ko'proq bog'liqdir. Bundan tashqari, melatonin darajasining pasayish bosqichi melatonin sintezining tugashiga qaraganda ancha ishonchli va barqarordir.

Sirkadiyalik ritmga ko'ra sodir bo'ladigan boshqa fiziologik o'zgarishlar kiradi yurak urish tezligi va ko'plab uyali jarayonlar ", shu jumladan oksidlovchi stress, hujayra metabolizmi immunitet va yallig'lanish reaktsiyalari, epigenetik o'zgartirish, gipoksiya /giperoksiya javob berish yo'llari, endoplazmatik retikulyar stress, avtofagiya va tartibga solish ildiz hujayrasi atrof-muhit. "[90] Yigitlarni o'rganish paytida, yurak urish tezligi uxlash vaqtida o'rtacha eng past ko'rsatkichga va uyg'onganidan ko'p o'tmay eng yuqori ko'rsatkichga erishishi aniqlandi.[91]

Oldingi tadqiqotlarga zid ravishda, tana haroratining psixologik testlarda ishlashga ta'siri yo'qligi aniqlandi. Bu, avvalgi tadqiqotlarda ko'rib chiqilgan funktsiyalarning boshqa sohalariga nisbatan yuqori bilim funktsiyasi uchun evolyutsion bosim tufayli yuzaga kelishi mumkin.[92]

"Asosiy soat" dan tashqarida

Oz-ozdan mustaqil sirkadiyalik ritmlar suprachiasmatik yadrolardan (SCN) tashqaridagi tanadagi ko'plab organlar va hujayralarda uchraydi, "master soat". Darhaqiqat, nevrolog olim Jozef Takaxashi va uning hamkasblari 2013 yilgi maqolasida "tanadagi deyarli har bir hujayrada sirkadiyalik soat bor" deb ta'kidlagan edi.[93] Masalan, periferik osilator deb ataladigan bu soatlar buyrak usti bezidan topilgan, qizilo'ngach, o'pka, jigar, oshqozon osti bezi, taloq, timus va teri.[94][95][96] Xushbo'y lampochkaning mavjudligiga oid ba'zi dalillar mavjud[97] va prostata[98] hech bo'lmaganda madaniylashtirilganda tebranishlarga duch kelishi mumkin.

Teridagi osilatorlar nurga ta'sir etsa-da, tizimli ta'sir isbotlanmagan.[99] Bundan tashqari, masalan, jigar hujayralari kabi ko'plab osilatorlar yorug'likdan tashqari, masalan, oziqlantirish kabi kirishga javob berishi aniqlangan.[100]

Nur va biologik soat

Yorug'lik biologik soatni qayta tiklaydi fazali javob egri chizig'i (XXR). Vaqtga qarab, yorug'lik sirkadiyalik ritmni oshirishi yoki kechiktirishi mumkin. Ham XXR, ham talab qilinadi yorug'lik turlardan turlarga farq qiladi va soatlarni qayta tiklash uchun yorug'likning past darajalari talab qilinadi tungi kemiruvchilar odamlarga qaraganda.[101]

Uzunroq yoki qisqaroq tsikllar

Odamlar ustida olib borilgan turli xil tadqiqotlar majburiy uyqu / uyg'onish davrlarini 24 soatdan farq qiladi, masalan Nataniel Kleitman 1938 yilda (28 soat) va Derk-Yan Dijk va Charlz Chezler 1990-yillarda (20 soat). Because normal people cannot entrain to such abnormal day/night rhythms,[102] this is referred to as a forced desynchrony protocol. Under such a protocol, sleep and wake episodes are uncoupled from the body's endogenous circadian period, which allows researchers to assess the effects of circadian phase (i.e. the relative timing of the circadian cycle) on aspects of sleep and wakefulness including uyqu kechikishi and other functions - both physiological, behavioral, and cognitive.[103][104][105][106][107]

Inson salomatligi

A short nap during the day does not affect circadian rhythms.

Timing of medical treatment in coordination with the body clock, chronotherapeutics, may significantly increase efficacy and reduce drug toxicity or adverse reactions.[108]

A number of studies have concluded that a short period of sleep during the day, a power-nap, does not have any measurable effect on normal circadian rhythms but can decrease stress and improve productivity.[109][110][111]

Health problems can result from a disturbance to the circadian rhythm.[112] Circadian rhythms also play a part in the retikulyar faollashtiruvchi tizim, which is crucial for maintaining a state of consciousness. A reversal[tushuntirish kerak ] in the sleep–wake cycle may be a sign or complication of uremiya,[113] azotemiya yoki buyrakning o'tkir shikastlanishi.[114][115]

Studies have also shown that light has a to'g'ridan-to'g'ri ta'sir on human health because of the way it influences the circadian rhythms.[116]

Indoor lighting

Lighting requirements for circadian regulation are not simply the same as those for vision; planning of indoor lighting in offices and institutions is beginning to take this into account.[117] Animal studies on the effects of light in laboratory conditions have until recently considered light intensity (nurlanish ) but not color, which can be shown to "act as an essential regulator of biological timing in more natural settings".[118]

Obesity and diabetes

Semirib ketish va diabet are associated with lifestyle and genetic factors. Among those factors, disruption of the circadian clockwork and/or misalignment of the circadian timing system with the external environment (e.g., light–dark cycle) might play a role in the development of metabolic disorders.[112]

Smenali ish or chronic vaqt mintaqasi o'zgarishi xastaligi have profound consequences for circadian and metabolic events in the body. Animals that are forced to eat during their resting period show increased body mass and altered expression of clock and metabolic genes.[119][tibbiy ma'lumotnoma kerak ] In humans, shift work that favors irregular eating times is associated with altered insulin sensitivity and higher body mass. Shift work also leads to increased metabolic risks for cardio-metabolic syndrome, hypertension, and inflammation.[120]

Airline pilots and cabin crew

Due to the work nature of airline pilots, who often cross several time zones and regions of sunlight and darkness in one day, and spend many hours awake both day and night, they are often unable to maintain sleep patterns that correspond to the natural human circadian rhythm; this situation can easily lead to charchoq. The NTSB cites this as contributing to many accidents[121] and has conducted several research studies in order to find methods of combating fatigue in pilots.[122]

Buzilish

Disruption to rhythms usually has a negative effect. Many travelers have experienced the condition known as vaqt mintaqasi o'zgarishi xastaligi, with its associated symptoms of charchoq, disorientation, and uyqusizlik.[123]

A number of other disorders, for example bipolyar buzilish va ba'zilari uyqu buzilishi kabi kechiktirilgan uyqu fazasi buzilishi (DSPD), are associated with irregular or pathological functioning of circadian rhythms.[124]

Disruption to rhythms in the longer term is believed to have significant adverse health consequences for peripheral organs outside the brain, in particular in the development or exacerbation of cardiovascular disease.[112][125] Blue LED lighting suppresses melatonin production five times more than the orange-yellow high-pressure sodium (HPS) light; a metal halide lamp, which is white light, suppresses melatonin at a rate more than three times greater than HPS.[126] Depression symptoms from long term nighttime light exposure can be undone by returning to a normal cycle.[127]

Effect of drugs

Studies conducted on both animals and humans show major bidirectional relationships between the circadian system and abusive drugs. It is indicated that these abusive drugs affect the central circadian pacemaker. Individuals suffering from substance abuse display disrupted rhythms. These disrupted rhythms can increase the risk for substance abuse and relapse. It is possible that genetic and/or environmental disturbances to the normal sleep and wake cycle can increase the susceptibility to addiction.[128]

It is difficult to determine if a disturbance in the circadian rhythm is at fault for an increase in prevalence for substance abuse or if other environmental factors such as stress are to blame.Changes to the circadian rhythm and sleep occur once an individual begins abusing drugs and alcohol. Once an individual chooses to stop using drugs and alcohol, the circadian rhythm continues to be disrupted.[128]

The stabilization of sleep and the circadian rhythm might possibly help to reduce the vulnerability to addiction and reduce the chances of relapse.[128]

Circadian rhythms and clock genes expressed in brain regions outside the supraxiyazmatik yadro may significantly influence the effects produced by drugs such as kokain.[iqtibos kerak ] Moreover, genetic manipulations of clock genes profoundly affect cocaine's actions.[129]

Jamiyat va madaniyat

2017 yilda, Jeffri C. Xoll, Maykl V. Yang va Maykl Rosbash taqdirlandi Fiziologiya yoki tibbiyot bo'yicha Nobel mukofoti "for their discoveries of molecular mechanisms controlling the circadian rhythm".[130][131]

Shuningdek qarang

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