Activation of alpha 2A adrenoceptors alters dendritic spine development and the expression of spinophilin in cultured cortical neurones.

alpha2 adrenoceptors have been shown to regulate the development of dendrites in mammalian cortical neurones. In this study we have investigated how agonists of alpha2 adrenoceptors affect length and density of dendritic spines in cultured cortical neurones from C57/B6 mice. A twenty-four hour incubation of 14 day old cultured neurones with UK 14304, an alpha2-adrenoceptor agonist, resulted in a significant increase in the average length and density of dendritic spines. Furthermore, incubation of neurones with the selective alpha 2A agonist guanfacine resulted in 1.2-fold increase in spine length and 1.8-fold increase in spine density. These effects were blocked by RX 821002 and BRL 44408, alpha2- and alpha 2A-adrenoceptor antagonists, respectively. The observed changes in the density and length of dendritic spines were correlated with increased expression of spinophilin, a key cytoskeletal protein in the formation and maintenance of dendritic spines, and a decrease in the phosphorylation of spinophilin on serine residues. The latter finding points to a possible mechanism by which adrenoceptors may regulate spinophilin function in dendritic spine development and structure in cortical neurones in vitro.