Gulisano Walter, Bizzoca Antonella, Gennarini Gianfranco, Palmeri Agostino, Puzzo Daniela
Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
Section of Physiology, Department of Basic Medical Sciences, Neuroscience and Sensory Organs, University of Bari, Bari, Italy.
Mol Cell Neurosci. 2017 Jun;81:64-71. doi: 10.1016/j.mcn.2016.12.003. Epub 2016 Dec 28.
Cell adhesion molecules (CAMs) have a pivotal role in building and maintaining synaptic structures during brain development participating in axonal elongation and pathfinding, glial guidance of neuronal migration, as well as myelination. CAMs expression persists in the adult brain particularly in structures undergoing postnatal neurogenesis and involved in synaptic plasticity and memory as the hippocampus. Among the neural CAMs, we have recently focused on F3/Contactin, a glycosylphosphatidyl inositol-anchored glycoprotein belonging to the immunoglobulin superfamily, involved in neuronal development, synaptic maintenance and organization of neuronal networks. Here, we discuss our recent data suggesting that F3/Contactin exerts a role in hippocampal synaptic plasticity and memory in adult and aged mice. In particular, we have studied long-term potentiation (LTP), spatial and object recognition memory, and phosphorylation of the transcription factor cAMP-Responsive-Element Binding protein (CREB) in a transgenic mouse model of F3/Contactin overexpression. We also investigated whether F3/Contactin might influence neuronal apoptosis and the production of amyloid-beta peptide (Aβ), known to be one of the main pathogenetic hallmarks of Alzheimer's disease (AD). In conclusion, a further understanding of F3/Contactin role in synaptic plasticity and memory might have interesting clinical outcomes in cognitive disorders, such as aging and AD, offering innovative therapeutic opportunities.
细胞黏附分子（CAMs）在大脑发育过程中构建和维持突触结构方面发挥着关键作用，参与轴突伸长和路径寻找、神经元迁移的胶质引导以及髓鞘形成。CAMs的表达在成人大脑中持续存在，特别是在经历出生后神经发生且参与突触可塑性和记忆的结构中，如海马体。在神经CAMs中，我们最近聚焦于F3/Contactin，它是一种糖基磷脂酰肌醇锚定糖蛋白，属于免疫球蛋白超家族，参与神经元发育、突触维持和神经网络的组织。在这里，我们讨论我们最近的数据，这些数据表明F3/Contactin在成年和老年小鼠的海马体突触可塑性和记忆中发挥作用。特别是，我们在F3/Contactin过表达的转基因小鼠模型中研究了长时程增强（LTP）、空间和物体识别记忆以及转录因子环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化。我们还研究了F3/Contactin是否可能影响神经元凋亡以及淀粉样β肽（Aβ）的产生，已知Aβ是阿尔茨海默病（AD）的主要致病标志之一。总之，进一步了解F3/Contactin在突触可塑性和记忆中的作用可能在认知障碍（如衰老和AD）中产生有趣的临床结果，提供创新的治疗机会。
