Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
Schizophr Bull. 2013 Jan;39(1):141-50. doi: 10.1093/schbul/sbr076. Epub 2011 Jul 28.
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.
神经颗粒蛋白（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。NRGN 基因中 rs12807809 的遗传变异最近在全基因组关联研究的荟萃分析中被证实与精神分裂症有关：T 等位基因被发现与精神分裂症在全基因组范围内显著相关。在一个大的健康受试者样本中进行了认知测试和人格问卷。在一个亚样本中，在进行情景记忆编码和检索任务时，使用功能磁共振成像（fMRI）测量大脑激活。所有受试者均对 NRGN rs12807809 进行了基因分型。在大样本中，基因型对人格或认知测量没有影响。T 等位基因纯合子携带者在 fMRI 检索任务中的表现更好。在控制记忆表现后，在前扣带皮层的编码和后扣带区域的检索过程中，出现了明显的大脑激活差异。我们可以证明 NRGN 的 rs12807809 与前扣带和后扣带的神经功能差异有关。这些区域参与情景记忆过程，并且在结构和功能成像以及尸检研究中与精神分裂症的病理生理学有关。
