The Role Of α_2A-adrenoceptors In The Development Of Dendritic Spines Of Medial Prefrontal Cortical Neurons

The prefrontal cortex (PFC) plays a vital role in many higher brain functions. It has been demonstrated that norepinephrine (NE) exerts a beneficial influence on PFC cognitive functions via actions at postsynaptic a2A-adrenoceptors (α2A-ARs). Dendritic spines are tiny protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain, and they play an important role in synaptic transmission and plasticity. Previous studies implicate a role of a2A-ARs in the development of dendrites, but the underlying mechanism is still unclear. Here, we examined the role of a2A-ARs in the development/maturation of dendritic spines of medial prefrontal cortical (mPFC) neurons in culture, using immunostaining, western blotting, confocal laser scanning and RNAi technology. The main results are as follows:1.α2A-ARs are expressed in cultured neurons of mPFC. We used immunofluorescence technology to label mPFC neurons, scanned the neurons with confocal laser scanning microscope, and found that a2A-ARs were richly present in mPFC neurons.2. Stimulation of a2A-ARs, using the selective agonist guanfacine, promoted the growth of dendrites, increased the length and number of dendritic branch, enhanced the expression of PSD95(post-synaptic protein) but not synapsin I (pre-synaptic protein).3. The a2A-AR RNAi plasmid and lentivirus vector were successfully constructed. Western blotting showed that the expression of a2A-AR in mPFC neurons transferred α2A-AR RNAi plasmid or lentivirus vector was significantly decreased, which established a solid basis for analyzing the signaling mechanisms for the promotion of α2A-ARs in maturation of dendritic spines.