Dendritic spines are tiny protrusions along dendrites that receive excitatory synaptic inputs and compartmentalize postsynaptic responses in the mature brain. It is known that change in spine morphology is associated with brain functions such as learning and memory. α(2A)-Adrenoceptors (α(2A)-ARs) are highly expressed in cortical neurons and play important roles in neuronal differentiation, growth and neurotrophy. However, little is known about the role of α(2A)-ARs in the maturation of dendritic spines. Here, we report that stimulation of α(2A)-ARs promotes the maturation of dendritic spines in cultured neurons of the medial prefrontal cortex of rodents. Our results show that, stimulation of α(2A)-ARs by guanfacine induced significantly more stubby or mushroom spines in cultured mPFC neurons, with an enlargement of the spine head size. In parallel, the expression of PSD95 (a postsynaptic protein) in guanfacine-treated neurons was enhanced, while that of synapsin (a pre-synaptic protein) kept unchanged. These effects of guanfacine were blocked by co-administered yohimbine, a non-selective α(2)-AR antagonist. The present results implicate a prominent role of α(2A)-ARs in regulating the maturation of dendritic spines in the mPFC.
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