The neural network undergoes remodeling in response to neural activity and interventions, such as antidepressants. Cell adhesion molecules that link pre- and post-synaptic membranes are responsible not only for the establishment of the neural circuitry, but also for the modulation of the strength of each synaptic connection. Among the various classes of synaptic cell adhesion molecules, a non-clustered protocadherin, Arcadlin/Paraxial protocadherin/Protocadherin-8 (Acad), is unique in that it is induced quickly in response to neural activity. Although the primary structure of Arcadlin implies its cell adhesion activity, it weakens the adhesion of N-cadherin. Furthermore, Arcadlin reduces the dendritic spine density in cultured hippocampal neurons. In order to gain an insight into the function of Arcadlin in the brain, we examined the dendritic morphologies of the hippocampal neurons in Acad^−/− mice. Acad^−/− mice showed a higher spine density than wild-type mice. Following an electroconvulsive seizure (ECS), which strongly induces Arcadlin in the hippocampus, the spine density gradually decreased for 8 h. ECS did not reduce the spine density of CA1 apical dendrites in Acad^−/− mice. Daily intraperitoneal injection of the antidepressant fluoxetine (25 mg/kg/day) for 18 days resulted in the induction of Arcadlin in the hippocampus. This treatment reduced spine density in the dentate gyrus and CA1. Chronic fluoxetine treatment did not suppress spine density in Acad^−/− mice, suggesting that fluoxetine-induced decrease in spine density is largely due to Arcadlin. The present findings confirm the spine-repulsing activity of Arcadlin and its involvement in the remodeling of hippocampal neurons in response to antidepressants.

响应于神经活动和干预措施（例如抗抑郁药），神经网络将进行重塑。连接突触前和突触后膜的细胞粘附分子不仅负责神经回路的建立，而且还负责调节每个突触连接的强度。在各种类型的突触细胞粘附分子中，非聚集的原钙粘蛋白Arcadlin /旁轴原钙粘蛋白/ Procadcadherin-8（Acad）是独特的，因为它可以响应神经活动而快速诱导。虽然Arcadlin的一级结构暗示其细胞粘附活性，但它会减弱N-钙粘蛋白的粘附。此外，Arcadlin可降低培养的海马神经元中的树突棘密度。为了深入了解Arcadlin在大脑中的功能，Acad ^-/-小鼠。Acad ^-/-小鼠的脊柱密度比野生型小鼠高。电痉挛性癫痫发作（ECS）强烈诱导海马中的Arcadlin发作后，脊柱密度逐渐降低8小时。ECS并未降低Acad ^-/-小鼠中CA1顶端树突的脊柱密度。每天腹膜内注射抗抑郁药氟西汀（25 mg / kg /天），持续18天，导致海马中Arcadlin的诱导。这种治疗降低了齿状回和CA1中的脊柱密度。慢性氟西汀治疗不能抑制Acad ^-/-的脊柱密度小鼠，表明氟西汀诱导的脊柱密度降低很大程度上归因于Arcadlin。本研究结果证实了Arcadlin的抗脊柱活动及其在抗抑郁药应答中参与海马神经元重塑的作用。