Department of Physiology, University of Tartu Tartu, Estonia.
Front Pharmacol. 2013 Mar 26;4:32. doi: 10.3389/fphar.2013.00032. eCollection 2013.
The studies performed in laboratory animals and psychiatric patients suggest a possible role of limbic system-associated membrane protein (LAMP) in the mechanisms of psychiatric disorders. Stressful manipulations and genetic invalidation have revealed a role of the Lsamp gene in the regulation of anxiety in rodents. Besides that, Lsamp-deficient mice display reduced aggressiveness and impaired adaptation in novel and stressful environments. The behavioral effects of amphetamine were blunted in genetically modified mice. Recent pharmacological and biochemical studies point toward altered function of GABA-, 5-hydroxytryptamine-, and dopaminergic systems in Lsamp-deficient mice. Moreover, we found an association between the gene polymorphisms of LSAMP and major depressive disorder (MDD). Patients suffering from MDD had significantly increased ratio between risk and protective haplotypes of the LSAMP gene compared to healthy volunteers. However, the impact of these haplotypes for the function of LAMP is not clear and remains to be elucidated in future studies.
实验室动物和精神疾病患者的研究表明,边缘系统相关膜蛋白(LAMP)可能在精神疾病的发病机制中发挥作用。应激操作和基因失活揭示了 Lsamp 基因在调节啮齿动物焦虑中的作用。此外,Lsamp 缺陷小鼠表现出攻击性降低和在新的和应激环境中适应能力受损。基因修饰小鼠的安非他命的行为效应减弱。最近的药理学和生化研究表明,Lsamp 缺陷小鼠的 GABA、5-羟色胺和多巴胺能系统的功能发生改变。此外,我们发现 LSAMP 基因的基因多态性与重度抑郁症(MDD)之间存在关联。与健康志愿者相比,患有 MDD 的患者 LSAMP 基因的风险和保护单倍型之间的比值显著增加。然而,这些单倍型对 LAMP 功能的影响尚不清楚,有待进一步研究阐明。