Einat Haim, Manji Husseini K
College of Pharmacy, Duluth, University of Minnesota, 55812, USA.
Biol Psychiatry. 2006 Jun 15;59(12):1160-71. doi: 10.1016/j.biopsych.2005.11.004. Epub 2006 Feb 2.
Despite extensive research, the molecular/cellular underpinnings of bipolar disorder (BD) remain to be fully elucidated. Recent data has demonstrated that mood stabilizers exert major effects on signaling that regulate cellular plasticity; however, a direct extrapolation to mechanisms of disease demands proof that manipulation of candidate genes, proteins, or pathways result in relevant behavioral changes.
We critique and evaluate the behavioral changes induced by manipulation of cellular plasticity cascades implicated in BD.
Not surprisingly, the behavioral data suggest that several important signaling molecules might play important roles in mediating facets of the complex symptomatology of BD. Notably, the protein kinase C and extracellular signal-regulated kinase cascades might play important roles in the antimanic effects of mood stabilizers, whereas glycogen synthase kinase (GSK)-3 might mediate facets of lithium's antimanic/antidepressant actions. Glucocorticoid receptor (GR) modulation also seems to be capable to inducing affective-like changes observed in mood disorders. And Bcl-2, amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, and inositol homeostasis represent important pharmacological targets for mood stabilizers, but additional behavioral research is needed to more fully delineate their behavioral effects.
Behavioral data support the notion that regulation of cellular plasticity is involved in affective-like behavioral changes observed in BD. These findings are leading to the development of novel therapeutics for this devastating illness.
尽管进行了广泛研究，但双相情感障碍（BD）的分子/细胞基础仍有待充分阐明。最近的数据表明，心境稳定剂对调节细胞可塑性的信号传导有重大影响；然而，要直接推断其疾病机制，需要证明对候选基因、蛋白质或信号通路的操纵会导致相关行为变化。
我们对操纵与BD相关的细胞可塑性级联反应所诱导的行为变化进行了批判和评估。
毫不奇怪，行为数据表明，几种重要的信号分子可能在介导BD复杂症状的各个方面发挥重要作用。值得注意的是，蛋白激酶C和细胞外信号调节激酶级联反应可能在心境稳定剂的抗躁狂作用中发挥重要作用，而糖原合酶激酶（GSK）-3可能介导锂盐抗躁狂/抗抑郁作用的各个方面。糖皮质激素受体（GR）调节似乎也能够诱导心境障碍中观察到的情感样变化。并且Bcl-2、氨基-3-羟基-5-甲基异恶唑-4-丙酸受体和肌醇稳态是心境稳定剂的重要药理学靶点，但需要更多行为学研究来更全面地描述它们的行为效应。
行为数据支持细胞可塑性调节参与BD中观察到的情感样行为变化这一观点。这些发现正促使针对这种毁灭性疾病开发新的治疗方法。
