Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
Molecular and Developmental Neurobiology Research Group, Universitat de Lleida - IRBLleida, Office 1.13, Lab. 1.06. Avda. Rovira Roure, 80, 25198, Lleida, Spain.
Sci Rep. 2018 Feb 27;8(1):3703. doi: 10.1038/s41598-018-22030-4.
The Fibronectin Leucine-Rich Transmembrane protein 2 (FLRT2) has been implicated in several hormone -and sex-dependent physiological and pathological processes (including chondrogenesis, menarche and breast cancer); is known to regulate developmental synapses formation, and is expressed in the hippocampus, a brain structure central for learning and memory. However, the role of FLRT2 in the adult hippocampus and its relevance in sex-dependent brain functions remains unknown. We here used adult single-allele FLRT2 knockout (FLRT2) mice and behavioral, electrophysiological, and molecular/biological assays to examine the effects of FLRT2 haplodeficiency on synaptic plasticity and hippocampus-dependent learning and memory. Female and male FLRT2 mice presented morphological features (including body masses, brain shapes/weights, and brain macroscopic cytoarchitectonic organization), indistinguishable from their wild type counterparts. However, in vivo examinations unveiled enhanced hippocampus-dependent spatial memory recall in female FLRT2 animals, concomitant with augmented hippocampal synaptic plasticity and decreased levels of the glutamate transporter EAAT2 and beta estrogen receptors. In contrast, male FLRT2 animals exhibited deficient memory recall and decreased alpha estrogen receptor levels. These observations propose that FLRT2 can regulate memory functions in the adulthood in a sex-specific manner and might thus contribute to further research on the mechanisms linking sexual dimorphism and cognition.
纤连蛋白富亮氨酸跨膜蛋白 2（FLRT2）参与了多种激素和性别依赖性的生理和病理过程（包括软骨生成、月经初潮和乳腺癌）；已知其可调节发育性突触形成，并在海马体中表达，海马体是学习和记忆的重要脑区。然而，FLRT2 在成年海马体中的作用及其与性别依赖性脑功能的相关性仍不清楚。我们使用成年单等位基因 FLRT2 敲除（FLRT2）小鼠以及行为、电生理和分子/生物学检测方法，研究了 FLRT2 单等位基因缺失对突触可塑性和海马体依赖性学习记忆的影响。雌性和雄性 FLRT2 小鼠的形态特征（包括体重、脑形状/重量和脑宏观细胞结构组织）与野生型小鼠无异。然而，体内检测显示雌性 FLRT2 动物的海马体依赖性空间记忆召回能力增强，同时伴有海马体突触可塑性增强和谷氨酸转运体 EAAT2 及β雌激素受体水平降低。相比之下，雄性 FLRT2 动物表现出记忆召回缺陷和α雌激素受体水平降低。这些观察结果表明，FLRT2 可以以性别特异性的方式调节成年期的记忆功能，因此可能有助于进一步研究性别二态性和认知之间的联系机制。
