Positive Effects of Tryptophan and Serotonin on Cognition during Aging and Related-Diseases

Abstract

[eng] The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays a role in a variety of physiological processes such as food intake, activity rhythms, sexual behaviour and emotional states as a result of its activity in various structures of the central nervous system. Among this functional heterogeneity, the serotonergic system plays a significant role on cognitive function, in particular by interacting with the cholinergic, glutamatergic, dopaminergic or GABAergic systems. Serotonin release increases in hippocampus during working memory task and extensive evidence suggests that different serotonin receptors have a differential a role in learning and memory. Serotonin is biosynthesized from the essential amino acid tryptophan and the effective amount of serotonin in vivo depends on the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in the synthesis of serotonin. The TPH activity increases after tryptophan ingestion, which shows that this rate-limiting enzyme is far from being saturated in normal conditions, and shows that the synthesis of serotonin can be modulated by tryptophan ingestion. Increased biodisponibility of tryptophan can increase the amount of serotonin in the brain which can improve cognitive performance. In fact, the greater conversion of tryptophan to serotonin in regions such as the hippocampus is consistent with its role as a key structure involved in cognitive functions such as learning and memory. The synthesis of serotonin decreases with age, partly as a consequence of reduced plasma tryptophan by its degradation to kynurenic acid derivatives; and partly due to the proved susceptibility of TPH enzyme to oxidative damage by reactive oxygen species. In this way, a reduced TPH activity could explain the decrease in serotonin brain in aging. Thus, some studies suggest that treatments aimed at modulating the tryptophan in the brain, as well as modulating the activity of TPH enzyme produce a restorative effect of cognitive functions, which are impaired in aging. Accordingly with the free radical theory of aging, dietary antioxidants manipulations are expected to counteract the rate of production of free radicals and the associated damage. In this manner, the administration of antioxidants may restore TPH activity and thus serotonergic functions in brain. This chapter deals with the effects of tryptophan as well as some strategies or treatments that modify serotonin levels on cognitive processes during aging and neurodegenerative diseases.