因一种染色体变异而患上精神分裂症的患者会出现认知和精神方面的症状。如今,研究人员在日前在线出版的《自然—神经学》期刊上报告说,神经发育和连接过程中出现的变化可能与这些症状的出现有关。新发现为深入理解这些变异的神经性后果提供了一些线索。
在高加索人种中,12%的精神分裂症患者与22号染色体的一段缺失有关;在22号染色体的特定部位缺失的人群中,大约30%的人会出现精神分裂症,许多人会有认知缺陷。Maria Karayiorgou和同事培育了一种染色体微切除的小鼠,并研究其大脑海马区的神经发育和连接。他们报告说,携带这种切除的小鼠的神经细胞连接减少了,神经细胞的枝状生长状态也萎缩了。他们将这种缺失与微切除所导致的特定酶的丧失联系起来,这种酶与脂肪酸基团添加到某种蛋白质上有关。(生物谷Bioon.com)
生物谷推荐原始出处:
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.