Ïîëíàÿ âåðñèÿ ñòðàíèöû  English  

Ðåãóëÿöèÿ õðîìàòèíà è äåïðåññèÿ ó ìûøåé

Lady, 14.04.2006 06:00
Ãðóïïîé ó÷åíûõ èç The University of Texas Southwestern Medical Center ïîëó÷åíû î÷åíü èíòåðåñíûå äàííûå î ðîëè èçìåíåíèé â ñòðóêòóðå õðîìàòèíà â ðåàêöèè îðãàíèçìà íà äëèòåëüíûé ñòðåññ.  êà÷åñòâå ìîäåëè òàêîãî ñòðåññà áûë âûáðàí ñòðåññ ïîä÷èíåíèÿ – ê ãðóïïå ìûøåé ëèíèè ÂL6\ Ñ57 íà ïðîòÿæåíèè 10 äíåé åæåäíåâíî íà 10 ìèíóò ïîäñàæèâàëè ìûøü èç âûñîêî àãðåññèâíîé ëèíèè CD1.  ýòèõ óñëîâèÿõ ìûøè-õîçÿåâà âåëè ñåáÿ ïî îòíîøåíèþ ê «÷óæàêó» êàê ìûøè âòîðîãî ñîðòà. Ïðè ýòîì ó ìûøåé íàáëþäàëîñü èçìåíåíèå ýêñïðåññèè ãåíà íåéðîòðîôè÷åñêîãî ôàêòîðà ìîçãà (BDNF) â ãèïïîêàìïå - óìåíüøèëàñü ýêñïðåññèÿ äâóõ èç ïÿòè àëüòåðíàòèâíûõ òðàíñêðèïòîâ ãåíà BDNF. Êàæäûé èç ýòèõ âàðèàíòîâ ìÐÍÊ BDNF òðàíñêðèáèðóåòñÿ ñ ñâîåãî ïðîìîòîðà è ýêñïåðèìåíòû ñ èììóíîïðåöèïèòàöèåé õðîìàòèíà (ChIP àíàëèç) ïîêàçàëè, ÷òî ñíèæåíèå ýêñïðåññèè ñâÿçàíî ñ óñèëåíèåì ìåòèëèðîâàíèÿ ãèñòîíîâ â îáëàñòè ïðîìîòîðîâ òðàíñêðèïòîâ ñ ñíèæåííîé â óñëîâèÿõ ñòðåññà ýêñïðåññèåé. Ýòîò ýôôåêò áûë îáðàòèìûì - ïîä äåéñòâèåì àíòèäåïðåññàíòà èìèïðàìèíà íàáëþäàëèñü ñíèæåíèå óðîâíÿ ñòðåññà ó ìûøåé è íîðìàëèçàöèÿ ýêñïðåññèè âñåõ òðàíñêðèïòîâ ãåíà BDNF. Íà óðîâíå õðîìàòèíà ýôôåêò èìèïðàìèíà áûë ñâÿçàí ñ ñíèæåíèåì àêòèâíîñòè äåàöåòèëàçû ãèñòîíîâ è ñ ïîâûøåíèåì óðîâíÿ àöåòèëèðîâàíèÿ ãèñòîíîâ - ïðè÷åì ñâåðõýêñïðåññèÿ äåàöåòèëàçû ãèñòîíîâ ïðàêòè÷åñêè ïîëíîñòüþ ñíèìàëî äåéñòâèå èìèïðàìèíà. Âñå ýòî ãîâîðèò î òîì, ÷òî â ðåãóëÿöèè ýêñïðåññèè ãåíîìà â óñëîâèÿõ õðîíè÷åñêîãî ñòðåññà âàæíóþ ðîëü ìîãóò èãðàòü ëîêàëüíûå èçìåíåíèÿ ñòðóêòóðû õðîìàòèíà, ñâÿçàííûå ñ íàðóøåíèåì áàëàíñà ìåæäó ìåòèëèðîâàííîé è àöåòèëèðîâàííîé ôîðìîé ãèñòîíîâ.
http://www.nature.com/neuro/journal/v9/n4/full/nn1659.html

êàòåãîðèÿ - 2
vrida2, 30.01.2022 01:32
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