Cellular Function Imaging Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Japan.
J Neurosci Res. 2013 Jun;91(6):737-44. doi: 10.1002/jnr.23209. Epub 2013 Mar 4.
The vascular serotonergic system in the brain has been implicated in the pathophysiology of migraine, however, involvement of the serotonergic nervous system of the brain parenchyma in the pathophysiology remains unclear. To investigate whether the brain parenchymal serotonergic nervous system is involved in the etiology of migraine, we prepared an experimental model of migraine by generation of cortical spreading depression (SD), characterized by spreading of neuronal/glial membrane depolarization accompanied by temporal elevation of the cerebral blood flow (CBF) throughout the cerebral cortical hemisphere in rats, which underwent pharmacological treatment for degeneration of serotonergic neurons in the dorsal raphe nucleus. We show here that (1) significant degeneration of serotonergic neurons in the dorsal raphe nucleus and serotonergic fibers in the cerebral cortex was observed in treated rats, (2) spreading velocity of the CBF changes was significantly increased in these rats, and (3) calculated width of the depolarization wave was significantly extended in these rats. These results indicate that the dorsal raphe serotonergic neurons modulate cortical spreading depression and might be involved in migraine pathology via a similar mechanism.
脑内的血管 5-羟色胺能系统与偏头痛的病理生理学有关，然而，脑实质的 5-羟色胺能神经系统在病理生理学中的参与仍不清楚。为了研究脑实质 5-羟色胺能神经系统是否参与偏头痛的病因，我们通过皮层扩散性抑制（CSD）的产生来制备偏头痛的实验模型，该模型的特征是神经元/神经胶质膜去极化的传播伴随着整个大脑皮质半球的脑血流（CBF）的暂时升高，这些大鼠接受了药物处理以导致中缝背核中 5-羟色胺能神经元的退化。我们在这里表明：（1）在接受治疗的大鼠中观察到中缝背核中的 5-羟色胺能神经元和大脑皮质中的 5-羟色胺能纤维明显退化；（2）这些大鼠的 CBF 变化的传播速度显著增加；（3）这些大鼠的去极化波的计算宽度显著延长。这些结果表明，中缝背核 5-羟色胺能神经元调节皮层扩散性抑制，并且可能通过类似的机制参与偏头痛的病理过程。
