Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Cognitive and Behavioral Sciences, Tehran University of Medical Sciences, Tehran, Iran.
J Mol Endocrinol. 2023 Jul 20;71(2). doi: 10.1530/JME-22-0161. Print 2023 Aug 1.
Arylalkylamine N-acetyltransferase (AANAT), a rate-limiting enzyme in melatonin synthesis, is present in extra-pineal tissues such as the hippocampus. The hippocampal AANAT activity in amyloid β (Aβ) neurotoxicity has not been exactly defined. Adult male rats received bilateral intra-CA1 Aβ administration. The hippocampus tissue sampling was performed 2, 12, and 24 h after Aβ injection in the morning and night. The inflammation was monitored using tumor necrosis factor-alpha (TNF-α) immunohistochemistry. The AANAT enzyme activity and melatonin levels were measured using western blotting and high-performance liquid chromatography. The sampling in the morning vs night showed no significant differences in the AANAT activity. The Aβ increased the area of TNF-α positive staining 24 h after injection, which indicated the induction of an inflammatory context. It was accompanied by a significant reduction in AANAT activity and hippocampal melatonin. A reverse correlation was also detected between TNF-α and AANAT activity in the 24-h group. The TNF-α positive area was significantly increased in the 24-h group as compared to the 12-h group. Data showed that inflammatory processes began 12 h after the Aβ injection and augmented 24 h later. In the second experiment, the impact of Aβ injection on hippocampus AANAT activity was examined in the pinealectomized (PIN×) animals. The PIN× per se did not affect the hippocampal AANAT and melatonin levels. However, there was a significant decrease in hippocampal melatonin in the PIN×+Aβ group. The findings suggest the accompanying hippocampal inflammatory context and AANAT enzyme activity reduction in early stages after Aβ administration. Understanding the underlying mechanism of the decreased AANAT activity may suggest new treatment strategies.
芳香族烷基胺 N-乙酰基转移酶（AANAT）是褪黑素合成的限速酶，存在于松果体外的组织中，如海马体。在淀粉样β（Aβ）神经毒性中，海马体的 AANAT 活性尚未得到明确界定。成年雄性大鼠接受双侧 CA1 内 Aβ 给药。海马组织采样在 Aβ 注射后早晨和晚上的 2、12 和 24 小时进行。使用肿瘤坏死因子-α（TNF-α）免疫组织化学监测炎症。使用 Western blot 和高效液相色谱法测量 AANAT 酶活性和褪黑素水平。与早晨相比，夜间采样显示 AANAT 活性没有明显差异。Aβ 在注射后 24 小时增加了 TNF-α 阳性染色的面积，表明诱导了炎症环境。这伴随着 AANAT 活性和海马褪黑素的显著降低。在 24 小时组中还检测到 TNF-α 和 AANAT 活性之间的反向相关性。与 12 小时组相比，24 小时组的 TNF-α 阳性面积显著增加。数据表明，炎症过程在 Aβ 注射后 12 小时开始，并在 24 小时后加剧。在第二个实验中，研究了 Aβ 注射对去松果体（PIN×）动物海马体 AANAT 活性的影响。PIN× 本身不会影响海马体的 AANAT 和褪黑素水平。然而，在 PIN×+Aβ 组中，海马体褪黑素含量显著降低。研究结果表明，在 Aβ 给药后早期，伴随海马体炎症环境和 AANAT 酶活性降低。了解降低的 AANAT 活性的潜在机制可能提示新的治疗策略。
