Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Mol Pharmacol. 2009 Jun;2(2):207-14. doi: 10.2174/1874467210902020207.
Bipolar disorder (BD) is a severe psychiatric illness characterized by recurrent manic and depressive episodes, without a characteristic neuropathology or clear etiology. Drugs effective in BD target many key signaling pathways in animal and cell studies. However, their mode of action in the BD brain remains elusive. In the rat brain, some of the mood stabilizers effective in treating mania (lithium, carbamazepine, valproate) or depression (lamotrigine) in BD are reported to decrease transcription of cytosolic phospholipase A(2) and cyclooxygenase-2 and to reduce levels of AP-2 and NF-kappaB, transcription factors of the two enzymes. The anti-manic drugs also decrease arachidonic acid (AA) turnover in brain phospholipids when given chronically to rats. Thus, drugs effective in BD commonly target AA cascade kinetics as well as AA cascade enzymes and their transcription factors in the rat brain. These studies suggest that of BD is associated with increased AA signaling in the brain. Developing therapeutic agents that suppress brain AA signaling could lead to additional treatments for BD. In this review, we discuss the mechanisms of action of mood stabilizers and the effects of docosahexaenoic acid on AA cascade enzymes in relation to BD.
双相情感障碍 (BD) 是一种严重的精神疾病,其特征是反复发作的躁狂和抑郁发作,没有特征性的神经病理学或明确的病因。在动物和细胞研究中有效的治疗 BD 的药物靶向许多关键信号通路。然而,它们在 BD 大脑中的作用机制仍难以捉摸。在大鼠大脑中,一些在 BD 中有效治疗躁狂的心境稳定剂(锂、卡马西平、丙戊酸)或抑郁(拉莫三嗪)被报道可降低细胞质磷脂酶 A(2) 和环氧化酶-2 的转录,并降低 AP-2 和 NF-κB 的水平,这两种酶的转录因子。抗躁狂药物还可减少慢性给予大鼠时大脑磷脂中花生四烯酸 (AA) 的周转率。因此,在 BD 中有效的药物通常靶向 AA 级联动力学以及大鼠脑中的 AA 级联酶及其转录因子。这些研究表明,BD 与大脑中 AA 信号的增加有关。开发抑制大脑 AA 信号的治疗药物可能会为 BD 提供更多的治疗方法。在这篇综述中,我们讨论了心境稳定剂的作用机制以及二十二碳六烯酸 (DHA) 对 AA 级联酶的影响与 BD 的关系。