因一種染色體變異而患上精神分裂癥的患者會(huì)出現(xiàn)認(rèn)知和精神方面的癥狀,。如今，研究人員在日前在線出版的《自然—神經(jīng)學(xué)》期刊上報(bào)告說(shuō),，神經(jīng)發(fā)育和連接過(guò)程中出現(xiàn)的變化可能與這些癥狀的出現(xiàn)有關(guān)。新發(fā)現(xiàn)為深入理解這些變異的神經(jīng)性后果提供了一些線索,。
在高加索人種中,，12%的精神分裂癥患者與22號(hào)染色體的一段缺失有關(guān),；在22號(hào)染色體的特定部位缺失的人群中，大約30%的人會(huì)出現(xiàn)精神分裂癥,，許多人會(huì)有認(rèn)知缺陷,。Maria Karayiorgou和同事培育了一種染色體微切除的小鼠，并研究其大腦海馬區(qū)的神經(jīng)發(fā)育和連接,。他們報(bào)告說(shuō),，攜帶這種切除的小鼠的神經(jīng)細(xì)胞連接減少了，神經(jīng)細(xì)胞的枝狀生長(zhǎng)狀態(tài)也萎縮了,。他們將這種缺失與微切除所導(dǎo)致的特定酶的喪失聯(lián)系起來(lái),，這種酶與脂肪酸基團(tuán)添加到某種蛋白質(zhì)上有關(guān)。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience,，11, 1302 - 1310,，Maria Karayiorgou，Joseph A Gogos
Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion
Jun Mukai1, Alefiya Dhilla2, Liam J Drew1, Kimberly L Stark3, Luxiang Cao1, Amy B MacDermott1,4, Maria Karayiorgou3 & Joseph A Gogos1,4
Abstract
Individuals with 22q11.2 microdeletions have cognitive deficits and a high risk of developing schizophrenia. Here we provide evidence that primary hippocampal neurons from a mouse model of 22q11.2 deletion (Df(16)A+/- mice) have decreased density of dendritic spines and glutamatergic synapses, as well as impaired dendritic growth. These deficits were prevented by introduction of the enzymatically active ZDHHC8 palmitoyltransferase encoded by a gene in the 22q11.2 locus, and they were also observed in primary cultures from Zdhhc8-deficient mice. Many of these deficits were also present in the hippocampi of adult Df(16)A+/- and Zdhhc8-deficient mice. Finally, we provide evidence that PSD95 is one of the substrates of ZDHHC8. Our analysis reveals that 22q11.2 microdeletion results in deficits in neuronal development and suggests that impaired neuronal protein palmitoylation contributes to many of these deficits.
1 Department of Physiology and Cellular Biophysics, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
2 Department of Pharmacology, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, New York 10032, USA.
3 Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
4 Department of Neuroscience, College of Physicians & Surgeons, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
