Sano Hiromi, Nagai Yumiko, Miyakawa Tsuyoshi, Shigemoto Ryuichi, Yokoi Mineto
Molecular Neurogenetics Unit, HMRO, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Neurochem. 2008 Apr;105(2):546-56. doi: 10.1111/j.1471-4159.2007.05152.x. Epub 2007 Dec 6.
Cyclic nucleotide phosphodiesterase 10A (PDE10A) is a member of phosphodiesterase families that degrade cAMP and/or cGMP in distinct intracellular sites. PDE10A has a dual activity on hydrolysis of both cAMP and cGMP, and is prominently expressed in the striatum and the testis. Previous studies suggested that PDE10A is involved in regulation of locomotor activity and potentially related to psychosis, but concrete physiological roles of PDE10A remains elusive yet. In this study, we genetically inactivated PDE10A2, a prominent isoform of PDE10A in the brain, in mice, and demonstrate that PDE10A2 deficiency results in increased social interaction without any major influence on different other behaviors, along with increased levels of striatal cAMP. We also demonstrate that PDE10A2 is selectively distributed in medium spiny neurons, but not interneurons, of the striatal complex. Thus, our results establish a physiological role for PDE10A2 in regulating cAMP pathway and social interaction, and suggest that cAMP signaling cascade in striatal medium spiny neurons might be involved in regulating social interaction behavior in mice.
环核苷酸磷酸二酯酶10A（PDE10A）是磷酸二酯酶家族的一员，可在不同的细胞内位点降解环磷酸腺苷（cAMP）和/或环磷酸鸟苷（cGMP）。PDE10A对cAMP和cGMP的水解均具有双重活性，且在纹状体和睾丸中显著表达。先前的研究表明，PDE10A参与运动活动的调节，并且可能与精神病有关，但PDE10A具体的生理作用仍不清楚。在本研究中，我们通过基因手段使小鼠脑中PDE10A的主要亚型PDE10A2失活，并证明PDE10A2缺陷导致社交互动增加，而对其他不同行为没有任何重大影响，同时纹状体cAMP水平升高。我们还证明，PDE10A2选择性地分布在纹状体复合体的中型多棘神经元中，而非中间神经元中。因此，我们的结果确立了PDE10A2在调节cAMP途径和社交互动中的生理作用，并表明纹状体中型多棘神经元中的cAMP信号级联可能参与调节小鼠的社交互动行为。
