Simplified dietary acute tryptophan depletion: effects of a novel amino acid mixture on the neurochemistry of C57BL/6J mice

Abstract

BackgroundDiet and nutrition can impact on the biological processes underpinning neuropsychiatric disorders. Amino acid (AA) mixtures lacking a specific neurotransmitter precursor can change the levels of brain serotonin (5-HT) or dopamine (DA) in the central nervous system. The availability of these substances within the brain is determined by the blood–brain barrier (BBB) that restricts the access of peripheral AA into the brain. AA mixtures lacking tryptophan (TRP) compete with endogenous TRP for uptake into the brain across the BBB, which in turn leads to a decrease in central nervous 5-HT synthesis.ObjectiveThe present study compared the effects of a simplified acute tryptophan depletion (SATD) mixture in mice on blood and brain serotonergic and dopaminergic metabolites to those of a commonly used acute tryptophan depletion mixture (ATD Moja-De) and its TRP-balanced control (BAL).DesignThe SATD formula is composed of only three large neutral AAs: phenylalanine (PHE), leucine (LEU), and isoleucine (ILE). BAL, ATD Moja-De, or SATD formulas were delivered to adult male C57BL/6J mice by gavage. TRP, monoamines, and their metabolites were quantified in blood and brain regions (hippocampus, frontal cortex, amygdala, caudate putamen, and nucleus accumbens).ResultsBoth ATD Moja-De and SATD significantly decreased levels of serum and brain TRP, as well as brain 5-HIAA and 5-HT compared with BAL. SATD reduced HVA levels in caudate but did not alter total DA levels or DOPAC. SATD decreased TRP and serotonergic metabolites comparably to ATD Moja-De administration.ConclusionA simplified and more palatable combination of AAs can manipulate serotonergic function and might be useful to reveal underlying monoamine-related mechanisms contributing to different neuropsychiatric disorders.

Cortico‐limbic connectivity in MAOA‐L carriers is vulnerable to acute tryptophan depletion

“…Tryptophan levels in blood serum decreased to about a third after ATD. Such a reduction of tryptophan confers to diminished central 5‐HT availability [Sánchez et al, ]. In the BAL condition, serum tryptophan after BAL increased to about the 6‐fold level of before beverage intake, similarly to a previous study by Dingerkus et al [2002].…”

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

“…Tryptophan is a substrate for the large neutral amino-acid transporter system and competes for transport with several other amino acids essential for brain function. This competition for transport is the basis for some acute tryptophan depletion diets (e.g., [ 10 ]). It is generally accepted that most of our tryptophan is bound to plasma albumin and hence is unavailable for transport into the brain.…”

Estudo Do L-Triptofano Na Depressão Ocorrida Pela Doença De Alzheimer Em Modelos Experimentais

“…A existência de glicocorticoides ou corticosteroides também pode estar envolvida na depressão, visto que seu excesso restringe os níveis de dopamina 13,14 . A serotonina ou 5-hidroxitriptamina (5-HT) é sintetizada nos neurônios da rafe presentes no tronco cerebral através da hidroxilação e descarboxilação do L-triptofanoaminoácido essencial considerado o único precursor da 5-HT produzido tanto no sistema nervoso central (SNC) quanto perifericamente, além de ter função na formação das proteínas e metabólitos como a quinurenina [15][16][17] . Por meio de uma rede difusa dentro do SNC o sistema serotoninérgico é encarregado por regular diversas funções, entre elas, o sono, apetite, temperatura, humor e cognição 16 .…”