The Effect of Neurogranin on Neural Correlates of Episodic Memory Encoding and Retrieval
The Effect of Neurogranin on Neural Correlates of Episodic Memory Encoding and Retrieval
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DOI：
10.1093/schbul/sbr076
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发表时间：
2013-01-01
影响因子：
6.6
通讯作者：
Kircher, Tilo
中科院分区：
文献类型：
--
作者：
Krug, Axel;Krach, Soeren;Kircher, Tilo
Neurogranin (NRGN) 是调节神经元中钙调蛋白-Ca(2+) 可用性的主要突触后蛋白。 NRGN 仅在大脑中表达，特别是在树突棘中，并且与空间学习和海马可塑性有关。最近，在全基因组关联研究的荟萃分析中，NRGN基因rs12807809的遗传变异被证实与精神分裂症相关：发现T等位基因在全基因组范围内与精神分裂症显着相关。对大量健康受试者进行了认知测试和性格问卷调查。在子样本中进行情景记忆编码和检索任务期间，通过功能磁共振成像（fMRI）测量大脑激活情况。所有受试者均进行了 NRGN rs12807809 基因分型。在大样本中，基因型对人格或认知测量没有影响。 T 等位基因的纯合子携带者在功能磁共振成像期间的检索任务中表现出更好的表现。在控制记忆表现后，在检索过程中，前扣带皮层的编码区和后扣带皮层的大脑激活差异明显。我们可以证明 NRGN 的 rs12807809 与前扣带回和后扣带回的差异神经功能相关。这些区域涉及情景记忆过程，并在结构和功能成像以及死后研究中与精神分裂症的病理生理学有关。
Neurogranin (NRGN) is the main postsynaptic protein regulating the availability of calmodulin-Ca(2+) in neurons. NRGN is expressed exclusively in the brain, particularly in dendritic spines and has been implicated in spatial learning and hippocampal plasticity. Genetic variation in rs12807809 in the NRGN gene has recently been confirmed to be associated with schizophrenia in a meta-analysis of genome-wide association studies: the T-allele was found to be genome-wide significantly associated with schizophrenia. Cognitive tests and personality questionnaires were administered in a large sample of healthy subjects. Brain activation was measured with functional magnetic resonance imaging (fMRI) during an episodic memory encoding and retrieval task in a subsample. All subjects were genotyped for NRGN rs12807809. There was no effect of genotype on personality or cognitive measures in the large sample. Homozygote carriers of the T-allele showed better performance in the retrieval task during fMRI. After controlling for memory performance, differential brain activation was evident in the anterior cingulate cortex for the encoding and posterior cingulate regions during retrieval. We could demonstrate that rs12807809 of NRGN is associated with differential neural functioning in the anterior and posterior cingulate. These areas are involved in episodic memory processes and have been implicated in the pathophysiology of schizophrenia in structural and functional imaging as well as postmortem studies.