Doctoral Program in Biomedical Engineering, Faculty of Sciences and Technology, University of Coimbra, 3000-548 Coimbra, Portugal.
Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, 3000-548 Coimbra, Portugal.
Int J Mol Sci. 2023 Mar 22;24(6):6010. doi: 10.3390/ijms24066010.
Tryptophan (Tryp) is an essential amino acid and the precursor of several neuroactive compounds within the central nervous system (CNS). Tryp metabolism, the common denominator linking serotonin (5-HT) dysfunctions and neuroinflammation, is involved in several neuropsychiatric conditions, including neurological, neurodevelopmental, neurodegenerative, and psychiatric diseases. Interestingly, most of those conditions occur and progress in a sex-specific manner. Here, we explore the most relevant observations about the influence of biological sex on Tryp metabolism and its possible relation to neuropsychiatric diseases. Consistent evidence suggests that women have a higher susceptibility than men to suffer serotoninergic alterations due to changes in the levels of its precursor Tryp. Indeed, female sex bias in neuropsychiatric diseases is involved in a reduced availability of this amino acid pool and 5-HT synthesis. These changes in Tryp metabolism could lead to sexual dimorphism on the prevalence and severity of some neuropsychiatric disorders. This review identifies gaps in the current state of the art, thus suggesting future research directions. Specifically, there is a need for further research on the impact of diet and sex steroids, both involved in this molecular mechanism as they have been poorly addressed for this topic.
色氨酸（Tryp）是一种必需氨基酸，也是中枢神经系统（CNS）中几种神经活性化合物的前体。色氨酸代谢是将 5-羟色胺（5-HT）功能障碍和神经炎症联系起来的共同因素，参与了多种神经精神疾病，包括神经、神经发育、神经退行性和精神疾病。有趣的是，大多数这些疾病以性别特异性的方式发生和进展。在这里，我们探讨了生物学性别对色氨酸代谢的影响的最相关观察结果，以及其与神经精神疾病的可能关系。一致的证据表明，由于其前体色氨酸水平的变化，女性比男性更容易受到 5-羟色胺能改变的影响。事实上，神经精神疾病中的女性性别偏好在某种程度上涉及到这种氨基酸库和 5-HT 合成的减少。色氨酸代谢的这些变化可能导致一些神经精神疾病的发病和严重程度出现性别二态性。本综述确定了当前研究现状中的差距，从而提出了未来的研究方向。具体来说，需要进一步研究饮食和性激素对这一分子机制的影响，因为这两个因素在这个主题中都没有得到很好的解决。
