Heinla Indrek, Leidmaa Este, Kongi Karina, Pennert Airi, Innos Jürgen, Nurk Kaarel, Tekko Triin, Singh Katyayani, Vanaveski Taavi, Reimets Riin, Mandel Merle, Lang Aavo, Lilleväli Kersti, Kaasik Allen, Vasar Eero, Philips Mari-Anne
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu Tartu, Estonia.
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu Tartu, Estonia ; Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry Munich, Germany.
Front Neurosci. 2015 Jun 8;9:205. doi: 10.3389/fnins.2015.00205. eCollection 2015.
Limbic system associated membrane protein (Lsamp) gene is involved in behavioral adaptation in social and anxiogenic environments and has been associated with a broad spectrum of psychiatric diseases. Here we studied the activity of alternative promoters of Lsamp gene in mice in three rearing conditions (standard housing, environmental enrichment and social isolation) and in two different genetic backgrounds (129S6/SvEv and C57BL/6). Isolation had no effect on the expression levels of Lsamp. Environmental enrichment elevated the expression levels of Lsamp 1b transcript specifically in the hippocampus in B6 mice, and the same tendency existed across both mouse lines and both transcripts. Furthermore, we showed that the density of cells exhibiting 1b promoter activity is remarkably higher in the subgranular zone of the dentate gyrus in the hippocampal formation which is a specific area of enrichment-induced neurogenesis in adult rodents. On the contrary to 1b, 1a promoter is selectively active in the pyramidal and granule cell layers. We provide evidence that Lsamp modulates enrichment-induced activation of Bdnf as the enrichment-induced elevation of Bdnf in the hippocampus is significantly diminished in Lsamp-deficient mice; furthermore, a significant correlation was found between the expression levels of Lsamp and Bdnf transcripts in the hippocampus and frontal cortex. Significant strain differences in Lsamp expression were detected in the hippocampus, frontal cortex and thalamus that could be related to the different behavioral phenotype of B6 and 129Sv mice. Our data provides further evidence that LSAMP is implicated in the hippocampal connectivity and plasticity thereby modulating adaptability in changing environments.
边缘系统相关膜蛋白（Lsamp）基因参与社交和焦虑环境中的行为适应，并与多种精神疾病有关。在此，我们研究了在三种饲养条件（标准饲养、环境丰富和社会隔离）下以及两种不同遗传背景（129S6/SvEv和C57BL/6）的小鼠中Lsamp基因可变启动子的活性。隔离对Lsamp的表达水平没有影响。环境丰富特异性地提高了B6小鼠海马中Lsamp 1b转录本的表达水平，并且在两个小鼠品系和两种转录本中都存在相同的趋势。此外，我们发现，在海马结构齿状回的颗粒下区，表现出1b启动子活性的细胞密度显著更高，该区域是成年啮齿动物中富集诱导神经发生的特定区域。与1b相反，1a启动子在锥体细胞层和颗粒细胞层中选择性活跃。我们提供的证据表明，Lsamp调节富集诱导的Bdnf激活，因为在Lsamp缺陷小鼠中，海马中富集诱导的Bdnf升高显著降低；此外，在海马和额叶皮质中，Lsamp和Bdnf转录本的表达水平之间发现了显著相关性。在海马、额叶皮质和丘脑中检测到Lsamp表达存在显著的品系差异，这可能与B6和129Sv小鼠不同行为表型有关。我们的数据进一步证明，LSAMP与海马的连接性和可塑性有关，从而调节在不断变化的环境中的适应性。
