Adachi Naoki, Yoshimura Aya, Chiba Shuichi, Ogawa Shintaro, Kunugi Hiroshi
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda City, Hyogo, Japan.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
Neurosci Lett. 2018 Jan 1;662:44-50. doi: 10.1016/j.neulet.2017.10.006. Epub 2017 Oct 6.
Brain-derived neurotrophic factor (BDNF) critically controls the fate and function of the neuronal network and has received much attention as a target of many brain diseases. Dopaminergic system dysfunction has also been implicated in a variety of neuropsychiatric diseases. Rotigotine, a non-ergot dopamine receptor agonist, is used in the treatment of Parkinson's disease and restless legs syndrome. To investigate the effects of rotigotine on neuronal functions both in vivo and in vitro, rats and primary cortical neurons were administered rotigotine, and the mRNA and protein expression levels of BDNF, its receptor TrkB and downstream signaling molecules, and synaptic proteins were determined. We found that BDNF protein was increased in the cortex and hippocampus of rats after 7days of rotigotine treatment. In contrast, BDNF mRNAs were reduced 6h after rotigotine treatment in cultured neurons presumably through the transient suppression of neuronal activity. We identified differential expression of D1, D2, and D3 receptors in the rat brain and cultured neurons. The observed increase in the expression of BDNF protein in the cortex and hippocampus after subchronic administration of rotigotine suggests that it may exert its medical effect in part through improving BDNF function in the brain. In addition, our results highlight the complex relationships between rotigotine and BDNF expression, which depend on the brain region, time course, and dose of the drug.
脑源性神经营养因子（BDNF）对神经网络的命运和功能起着关键的调控作用，作为多种脑部疾病的靶点备受关注。多巴胺能系统功能障碍也与多种神经精神疾病有关。罗替戈汀是一种非麦角类多巴胺受体激动剂，用于治疗帕金森病和不宁腿综合征。为了研究罗替戈汀在体内和体外对神经元功能的影响，给大鼠和原代皮层神经元施用罗替戈汀，并测定BDNF及其受体TrkB、下游信号分子和突触蛋白的mRNA和蛋白表达水平。我们发现，罗替戈汀治疗7天后，大鼠皮层和海马中的BDNF蛋白增加。相反，在培养的神经元中，罗替戈汀治疗6小时后，BDNF mRNA减少，这可能是由于神经元活动的短暂抑制所致。我们确定了大鼠脑和培养神经元中D1、D2和D3受体的差异表达。亚慢性施用罗替戈汀后，皮层和海马中BDNF蛋白表达增加，这表明它可能部分通过改善脑中BDNF的功能发挥其医学作用。此外，我们的结果突出了罗替戈汀与BDNF表达之间复杂的关系，这种关系取决于脑区、时间进程和药物剂量。
