Fitzgerald Paul J
Department of Psychology, Texas A&M University, Room 3200 ILSB, College Station, TX 77843-4235, United States.
Med Hypotheses. 2014 Apr;82(4):462-9. doi: 10.1016/j.mehy.2014.01.026. Epub 2014 Jan 30.
It is well documented that norepinephrine (NE) releasing neurons in the locus coeruleus, a brainstem nucleus that is a major source of NE for the brain, degenerate during the progression of Parkinson's disease (PD). A number of studies also suggest that, as a result, there is less NE released in the brain during disease progression, which may contribute to the pathophysiology and symptomatology of PD. This paper puts forth the novel hypothesis that NE degeneration in PD is preceded by elevated NE signaling, mainly as a result of genetics, and that this elevation is a major etiological factor in the disease. In this scenario, long-term (if not lifelong) elevated NE signaling could eventually invoke compensatory mechanisms that result in noradrenergic, and possibly dopaminergic, cell death. Several lines of evidence are briefly reviewed on the relationship between NE signaling and PD, including studies of: the level of NE; drugs that increase or decrease NE signaling; the relationship between PD and bipolar disorder, hypertension, and obesity, since the latter three conditions may be associated with increased NE signaling; and the relationship between PD and psychological stress, since stress is associated with increased release of NE. Many of these studies support NE degeneration during the disease, although some are consistent with elevated NE signaling during disease progression. Because there are few data on the state of the NE system prior to disease onset, the central point of this paper that NE signaling is elevated prior to development of PD, remains largely hypothetical. If elevated NE signaling really is an etiological factor in this disease, then early identification of susceptible individuals and long-term treatment with NE transmission reducing drugs, may help prevent or slow progression of PD.
有充分文献记载，蓝斑中的去甲肾上腺素（NE）释放神经元会在帕金森病（PD）进展过程中发生退化，蓝斑是脑干中的一个核团，是大脑中NE的主要来源。多项研究还表明，因此在疾病进展过程中大脑中释放的NE减少，这可能导致PD的病理生理学和症状学。本文提出了一个新的假说，即PD中NE的退化之前存在NE信号升高，主要是由遗传因素导致，并且这种升高是该疾病的一个主要病因。在这种情况下，长期（如果不是终身）的NE信号升高最终可能引发代偿机制，导致去甲肾上腺素能，甚至可能是多巴胺能细胞死亡。本文简要回顾了关于NE信号与PD之间关系的几条证据，包括以下方面的研究：NE水平；增加或减少NE信号的药物；PD与双相情感障碍、高血压和肥胖之间的关系，因为后三种情况可能与NE信号增加有关；以及PD与心理压力之间的关系，因为压力与NE释放增加有关。这些研究中的许多都支持疾病期间NE的退化，尽管有些与疾病进展期间NE信号升高一致。由于在疾病发作前关于NE系统状态的数据很少，本文的核心观点即PD发病前NE信号升高在很大程度上仍然是假设性的。如果NE信号升高确实是这种疾病的一个病因，那么早期识别易感个体并使用减少NE传递的药物进行长期治疗，可能有助于预防或减缓PD的进展。
