Effects of acute and long-term chronic social stress and aging on cognition: involvement of novel synaptic cell adhesion molecules

Cell adhesion molecules (CAMs) play a pivotal role in synaptic plasticity and memory as they influence development, maintenance and remodelling of synaptic contacts. Novel synaptic CAMs, including neuroplastin, nectin, SynCAM, and neurexin/neuroligin, may be promising candidates for studies on cognition as they are synapse-specific and able to form and modulate new synapses. Furthermore, it is widely accepted that chronic stress (CS) and aging impair cognitive functions. The aims of the current study are (I) to assess the impact of aging and CS on cognitive performance, and (II) to study the contribution of CAMs in these processes. We subjected male CD1 mice to chronic social stress (CSS) and tested cognitive performance at different ages in a variety of behavioral paradigms. Brains were removed at different time points for analysis of hippocampal CAM expression levels, dendritic spine morphology and electrophysiological properties of hippocampal principal neurons. We were able to show that CSS has both short- and long-term effects on cognitive performance, which correlate with structural and functional parameters. CSS worsened memory performance both in the Morris Water Maze and during object recognition. These effects could still be observed 12 months after CSS. In addition, we could correlate these cognitive differences with altered CAM dynamics. Following acquisition, Nectin1, Nectin3 and Nlgn1 were found to be differenzially regulated in the hippocampus and prefrontal