Jayamohananan Hridya, Manoj Kumar Maneesha Kalappurackal, T P Aneesh
Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, India.
Adv Pharm Bull. 2019 Aug;9(3):374-381. doi: 10.15171/apb.2019.044. Epub 2019 Aug 1.
Neurological and psychiatric disorders occur in about 6 percent of the global population indicating a significant amount of people suffering from neurological disorder on a varying range in day to day life. On an extensive view, there is a critical requirement for the development of an alternative biomarker for these conditions. The thwart found in developing a biomarker is the difficulty in identifying a serum biomarker as these are mostly limited to the central nervous system (CNS). Serotonin being a neurotransmitter synthesized in the raphe nuclei of the brain could serve as an alternative biomarker. Here, the limitation is that it's quickly metabolized by the mitochondrial enzyme MAO to 5-hydroxy indole acetic acid (5HIAA). This subsequent metabolite can be used for the analysis of serotonin levels in brain by analysing its concentration in the cerebrospinal fluid (CSF). Many theories suggest that the variations in serotonin level could lead to the development of many neurological and psychiatric disorders like Alzheimer's disease (AD), schizophrenia, depression and so on. A decreased level is noticed in these patients but this could either be due to decreased production or increased reuptake of serotonin from the neuronal synapses. For instance, we know that a patient with depression shows a significant reduction in the levels of 5HIAA, due to the location of the raphe nuclei within regions of memory and cognition. Similarly, it does shows variation in AD and mild cognitive disorder. Evolving of 5HIAA as a biomarker, could be more delicate and enhanced strategy for monitoring these disorders.
神经和精神疾病约占全球人口的6%，这表明在日常生活中有相当数量的人在不同程度上患有神经疾病。从广泛的角度来看，迫切需要为这些疾病开发替代生物标志物。开发生物标志物的一个障碍是难以确定血清生物标志物，因为这些标志物大多局限于中枢神经系统（CNS）。血清素作为一种在大脑中缝核合成的神经递质，可以作为一种替代生物标志物。然而，其局限性在于它会被线粒体酶MAO迅速代谢为5-羟吲哚乙酸（5HIAA）。通过分析脑脊液（CSF）中5HIAA的浓度，可以用于分析大脑中血清素水平。许多理论表明，血清素水平的变化可能导致许多神经和精神疾病的发生，如阿尔茨海默病（AD）、精神分裂症、抑郁症等。在这些患者中观察到血清素水平降低，但这可能是由于血清素产生减少或从神经元突触的再摄取增加所致。例如，我们知道抑郁症患者的5HIAA水平显著降低，这是由于中缝核位于记忆和认知区域内。同样，它在AD和轻度认知障碍中也表现出变化。将5HIAA发展为生物标志物，可能是监测这些疾病更精细和有效的策略。
