Synaptic Adhesion Molecules, sleep and transcription of Neuroligin-2

Abstract

[eng] Sleep is a homeostatic resting process characterized by the activation of particular brain areas and specific electroencephalographic (EEG) architecture. Changes on neuronal synchronization typical of sleep will depend on plastic processes involving many synaptic molecules. Neurotransmitter receptors and synaptic adhesion molecules (SAMs) are proteins involved in shaping variations in neuronal activity. In fact, it has been seen that many SAMs and receptors are altered by sleep deprivation and that the loss of these molecules alters the EEG signal and sleep states. Therefore, it has been crucial to integrate on a review article all the information regarding the role of SAMs on regulating sleep, as well as the effect of prolonged wakefulness on their expression. Neuroligin (NLGN) is a protein family especially important because elements of this system can determine if a synapse is excitatory or inhibitory, what can be crucial for changes in neuronal activity during sleep. NLGN1 recruits glutamate receptors addressing the synapse specialization into an excitatory one, whereas NLGN2 recruits GABA or glycine receptors converting the synapse into inhibitory. Consequently, a laboratory section was devoted to analyse the presence of sleep-related transcriptional regulatory elements on Nlgn2 gene promoter, as well as and the functionality of some of them. On a selected region of Nlgn2 promoter, it was seen that CLOCK and BMAL1, RORα and RORβ had no activating effect on Eboxes and RORE, respectively. Nonetheless, these regulatory elements have been found in other promoter regions, which would be also interesting to analyse. Similarly, several other sleeprelated regulatory elements (GRE, CRE, Dbp, PPAR) were described in different promoter regions of Nlgn2 gene, a functionality in transcriptional activation that should be tested as well in the future. In conclusion, this study suggests that NLGN2 may be regulated by sleep-related factors which have been seen to change with sleep homeostasis and circadian variations. Therefore, taking into account the information compiled in the review and possible role of sleep-related regulatory elements on Nlgn2 gene, SAMs seem to have an important role on shaping sleep plastic changes and architecture.