icu天使綜合征(編輯修改稿)
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【文章內(nèi)容簡(jiǎn)介】 respectively. The imprinting control region (ICR) for the PWS–AS locus consists of two parts, with the more centromeric ponent functioning as the AS ICR. The two ICRs direct the allelespecific expression of imprinted genes within these regions (indicated by arrows。 not all genes in the region are shown). The SNRPN (small nuclear ribonucleoprotein polypeptide N)–SNURF (SNRPN upstream reading frame) gene produces a long and plex transcript that leads to the expression of not only SNURF–SNRPN, but also several small nucleolar RNAs (snoRNAs). This transcript is also thought to inhibit the expression of UBE3A from the paternal allele through an antisense mechanism. UBE3A expression has been shown to be regulated by MeCP2 (methylCpGbinding protein 2), as UBE3A mRNA levels are reduced in MeCP2deficient cells. This downregulation of expression correlates with a biallelic production of UBE3A antisense RNA and changes in chromatin structure, with increased acetylation and methylation of H3K4 (histone 3 lysine 4), and reduced methylation of H2K9 at the PWS–AS imprinting centre87. This indicates that MeCP2 might mediate the interpretation of imprinted DNAmethylation marks in this region, in bination with other chromatinbinding proteins. b | MeCP2 can also regulate gene expression and maternal imprinting through formation of a silent chromatin loop. The yellow and blue arrows indicate MeCP2interacting sequences that have been identified by chromatin immunoprecipitation. When MeCP2 is present (left panel), it interacts with sequences that are near the imprinted DLX5 (distalless homebox 5) and DLX6 genes and define the boundaries of an 11kb chromatin loop, the formation of which is induced by MeCP2 binding88. This leads to an integration of DLX5 and DLX6 into a loop of silent, methylated chromatin, and represses their expression. In neurons that are deficient for MeCP2 (right panel), the chromatin in this region is structured into a distinct conformation that corresponds to active chromatin loops, which are delimited by sequences (indicated by purple and orange arrows) that interact with chromatin factors. Therefore, in MeCP2deficient neurons, the expression of DLX5 and DLX6 is no longer repressed, which results in the overexpression of these genes. Part b is modified with permission from Nature Genetics Ref. 88 169。 (2005) Macmillan Publishers Ltd.2 LTP的機(jī)制 （作者bluebacopa）1973 年，Bliss 等在海兔海馬的單突觸傳入通路上給與短串強(qiáng)直刺激后，使突觸后細(xì)胞的興奮，突觸后電位出現(xiàn)長(zhǎng)達(dá)數(shù)天乃至數(shù)周的振幅增大，這種現(xiàn)象稱之為長(zhǎng)時(shí)程突觸增強(qiáng)（LTP）。從此，LTP 受到了神經(jīng)科學(xué)家的廣泛重視，認(rèn)為是學(xué)習(xí)和記憶的基本神經(jīng)基礎(chǔ)。191983 年，科學(xué)家發(fā)現(xiàn)NMDA（N—甲基—D—門冬氨酸）受體通道復(fù)合體在LTP 過(guò)程中起著重要作用。關(guān) 于LTP的誘導(dǎo)和形成機(jī)制，文獻(xiàn)上研究和討論最多的是哺乳動(dòng)物海馬CA1區(qū)的LTP。有關(guān)機(jī)制可以簡(jiǎn)略概括為：當(dāng)突觸前的傳入纖維受到高頻刺激時(shí)，興奮性 神經(jīng)遞質(zhì)谷氨酸從突觸前膜到突觸間隙，和突觸后膜上的N M D A受體結(jié)合，激活N M D A受體，使阻礙鈣離子內(nèi)流的鎂離子被移除，大量鈣離子內(nèi)流，激活細(xì)胞內(nèi)的一系列分子過(guò)程，最終形成LTP。關(guān)于LTP與LTD的分子機(jī)制,一般認(rèn)為突觸前谷氨酸(Glu)釋放與突觸后NMDA受體結(jié)合后導(dǎo)致的突 觸后 Ca2+的量的多少以及PPI活性的強(qiáng)弱有關(guān),例如高頻刺激引起高濃度Ca,激活CaCaM激酶Ⅱ,突觸蛋白磷酸化,導(dǎo)致LTP。而低頻刺激引起低濃度 Ca,優(yōu)先激活磷蛋白磷酸酶,使突觸蛋白去磷酸化,導(dǎo)致LTD。最近的觀察發(fā)現(xiàn),在LTP和LTD發(fā)生前,PPI由于內(nèi)源性抑制物 1(inhibitor1)的存在而處于低水平的或潛在的磷酸化狀態(tài)。當(dāng)?shù)皖l刺激時(shí)激活A(yù)MPA受體,使Ca2+輕
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