University of Bordeaux, Institut des Maladies Neurodegeneratives, Bordeaux, France.
Brain. 2011 Aug;134(Pt 8):2321-38. doi: 10.1093/brain/awr166. Epub 2011 Jul 8.
Morphine is endogenously synthesized in the central nervous system and endogenous dopamine is thought to be necessary for endogenous morphine formation. As Parkinson's disease results from the loss of dopamine and is associated with central pain, we considered how endogenous morphine is regulated in the untreated and l-DOPA-treated parkinsonian brain. However, as the cellular origin and overall distribution of endogenous morphine remains obscure in the pathological adult brain, we first characterized the distribution of endogenous morphine-like compound immunoreactive cells in the rat striatum. We then studied changes in the endogenous morphine-like compound immunoreactivity of medium spiny neurons in normal, Parkinson's disease-like and l-DOPA-treated Parkinson's disease-like conditions in experimental (rat and monkey) and human Parkinson's disease. Our results reveal an unexpected dramatic upregulation of neuronal endogenous morphine-like compound immunoreactivity and levels in experimental and human Parkinson's disease, only partially normalized by l-DOPA treatment. Our data suggest that endogenous morphine formation is more complex than originally proposed and that the parkinsonian brain experiences a dramatic upregulation of endogenous morphine immunoreactivity. The functional consequences of such endogenous morphine upregulation are as yet unknown, but based upon the current knowledge of morphine signalling, we hypothesize that it is involved in fatigue, depression and pain symptoms experienced by patients with Parkinson's disease.
吗啡在中枢神经系统内源性合成，内源性多巴胺被认为是内源性吗啡形成所必需的。由于帕金森病是由多巴胺的丧失引起的，并与中枢疼痛有关，我们考虑了未治疗和 l-DOPA 治疗的帕金森病大脑中内源性吗啡是如何调节的。然而，由于内源性吗啡样化合物在病理性成年大脑中的细胞起源和整体分布仍然不清楚，我们首先描述了内源性吗啡样化合物免疫反应性细胞在大鼠纹状体中的分布。然后，我们研究了正常、帕金森病样和 l-DOPA 治疗的帕金森病样条件下中脑多巴胺能神经元内源性吗啡样化合物免疫反应性的变化，这些条件在实验（大鼠和猴子）和人类帕金森病中存在。我们的结果显示，实验和人类帕金森病中神经元内源性吗啡样化合物免疫反应性和水平出人意料地显著上调，仅部分通过 l-DOPA 治疗得到正常化。我们的数据表明，内源性吗啡的形成比最初提出的更为复杂，帕金森病大脑经历了内源性吗啡免疫反应性的显著上调。这种内源性吗啡上调的功能后果尚不清楚，但根据目前对吗啡信号的了解，我们假设它与帕金森病患者所经历的疲劳、抑郁和疼痛症状有关。
