Department of Biology, Colby College, 5720 Mayflower Hill, Waterville, ME 04901, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2012 Apr;161(4):355-60. doi: 10.1016/j.cbpa.2011.12.005. Epub 2011 Dec 16.
Melatonin has both neuritogenic and neuroprotective effects in mammalian cell lines such as neuroblastoma cells. The mechanisms of action include receptor-coupled processes, direct binding and modulation of calmodulin and protein kinase C, and direct scavenging of free radicals. While melatonin is produced in invertebrates and has influences on their physiology and behavior, little is known about its mechanisms of action. We studied the influence of melatonin on neuritogenesis in well-differentiated, extensively-arborized crustacean x-organ neurosecretory neurons. Melatonin significantly increased neurite area in the first 24h of culture. The more physiological concentrations, 1 nM and 1 pM, increased area at 48 h also, whereas the pharmacological 1 μM concentration appeared to have desensitizing effects by this time. Luzindole, a vertebrate melatonin receptor antagonist, had surprising and significant agonist-like effects in these invertebrate cells. Melatonin receptors have not yet been studied in invertebrates. However, the presence of membrane-bound receptors in this population of crustacean neurons is indicated by this study. Melatonin also has significant neuroprotective effects, reversing the inhibition of neuritogenesis by 200 and 500 μM hydrogen peroxide. Because this is at least in part a direct action not requiring a receptor, melatonin's protection from oxidative stress is not surprisingly phylogenetically-conserved.
褪黑素在哺乳动物细胞系（如神经母细胞瘤）中具有神经营养和神经保护作用。其作用机制包括受体偶联过程、直接结合并调节钙调蛋白和蛋白激酶 C，以及直接清除自由基。虽然褪黑素在无脊椎动物中产生，并对其生理和行为产生影响，但对其作用机制知之甚少。我们研究了褪黑素对充分分化、广泛分枝的甲壳纲 x 器官神经分泌神经元的神经发生的影响。褪黑素在培养的前 24 小时内显著增加了神经突面积。更生理的浓度，1 nM 和 1 pM，在 48 小时时也增加了面积，而药理学 1 μM 浓度在此时似乎具有脱敏作用。Luzindole，一种脊椎动物褪黑素受体拮抗剂，在这些无脊椎动物细胞中具有惊人的、类似激动剂的作用。褪黑素受体尚未在无脊椎动物中进行研究。然而，本研究表明，甲壳纲神经元中存在膜结合受体。褪黑素还具有显著的神经保护作用，可逆转 200 和 500 μM 过氧化氢对神经突生成的抑制。由于这至少部分是一种不需要受体的直接作用，因此褪黑素对氧化应激的保护在进化上是保守的，这并不奇怪。
