Department of Psychiatry, University of Oxford, Oxford, UK.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Transl Psychiatry. 2018 Oct 22;8(1):229. doi: 10.1038/s41398-018-0288-2.
Transgenic mice overexpressing the type I isoform of neuregulin 1 (Nrg1; NRG1) have alterations in hippocampal gamma oscillations and an age-emergent deficit in hippocampus-dependent spatial working memory. Here, we examined the molecular and morphological correlates of these findings. Microarrays showed over 100 hippocampal transcripts differentially expressed in Nrg1 mice, with enrichment of genes related to neuromodulation and, in older mice, of genes involved in inflammation and immunity. Nrg1 mice had an enlarged hippocampus with a widened dentate gyrus. The results show that Nrg1 type I impacts on hippocampal gene expression and structure in a multifaceted and partly age-related way, complementing the evidence implicating Nrg1 signaling in aspects of hippocampal function. The findings are also relevant to the possible role of NRG1 signaling in the pathophysiology of schizophrenia or other disorders affecting this brain region.
过表达神经调节蛋白 1 （NRG1）I 型的转基因小鼠表现出海马γ 振荡的改变和海马依赖的空间工作记忆的年龄出现缺陷。在这里，我们研究了这些发现的分子和形态学相关性。微阵列显示，Nrg1 小鼠的海马体中有 100 多个转录本差异表达，与神经调节相关的基因富集，在老年小鼠中，与炎症和免疫相关的基因富集。Nrg1 小鼠的海马体体积增大，齿状回变宽。结果表明，Nrg1I 型以多方面且部分与年龄相关的方式影响海马体的基因表达和结构，补充了 NRG1 信号在海马体功能方面的作用的证据。这些发现也与 NRG1 信号在影响该脑区的精神分裂症或其他疾病的病理生理学中的可能作用有关。
