Gawryluk Jeremy W, Young L Trevor
Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T 2A1,
Curr Top Behav Neurosci. 2011;5:139-65. doi: 10.1007/7854_2010_71.
Signal transduction pathways and genes associated with cellular life and death have received much attention in bipolar disorder (BPD) and provide scientists with molecular targets for understanding the biological basis of BPD. In this chapter, we describe the signal transduction pathways involved in the molecular biology of BPD and the indications for the mechanisms of disease and treatment. We discuss the BPD literature with respect to the disease itself and the effects of mood stabilizer treatment on cellular receptors, including G-protein-coupled receptors, glutamate receptors, and tyrosine receptor kinase. We also discuss the intracellular alterations observed in BPD to second messenger systems, such as cyclic adenosine monophosphate (cAMP), protein kinase A, phosphoinositide pathways, glycogen synthase kinase-3, protein kinase B, Wnt, and arachidonic acid. We describe how receptor activation and modulation of second messengers occurs, and how transcription factors are activated and altered in this disease (e.g., the transcription factors ?-catenin, cAMP response element binding protein, heat shock transcription factor-1, and activator protein-1). Abnormalities in intracellular signal transduction pathways could generate a functional discrepancy in numerous neurotransmitter systems, which may explain the varied clinical symptoms observed in BPD. The influence of mood stabilizers on transcription factors may be important in connecting the regulation of gene expression to neuroplasticity and cellular resilience.
与细胞生死相关的信号转导通路和基因在双相情感障碍（BPD）中备受关注，为科学家理解BPD的生物学基础提供了分子靶点。在本章中，我们描述了BPD分子生物学中涉及的信号转导通路以及疾病机制和治疗的指征。我们讨论了关于BPD疾病本身以及心境稳定剂治疗对细胞受体（包括G蛋白偶联受体、谷氨酸受体和酪氨酸受体激酶）影响的文献。我们还讨论了在BPD中观察到的细胞内第二信使系统的改变，如环磷酸腺苷（cAMP）、蛋白激酶A、磷酸肌醇途径、糖原合酶激酶-3、蛋白激酶B、Wnt和花生四烯酸。我们描述了受体激活和第二信使调节是如何发生的，以及在这种疾病中转录因子是如何被激活和改变的（例如，转录因子β-连环蛋白、cAMP反应元件结合蛋白、热休克转录因子-1和激活蛋白-1）。细胞内信号转导通路的异常可能在众多神经递质系统中产生功能差异，这可能解释了在BPD中观察到的各种临床症状。心境稳定剂对转录因子的影响可能在将基因表达调控与神经可塑性和细胞复原力联系起来方面很重要。
