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

Sánchez CL, Van Swearingen AE, Arrant AE, Biskup CS, Kuhn CM, Zepf FD - Food Nutr Res (2015)

Bottom Line: Both 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.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JARA Brain, RWTH Aachen University, Aachen, Germany.

ABSTRACT

Background: Diet 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.

Objective: The 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).

Design: The 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).

Results: Both 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.

Conclusion: A 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.

No MeSH data available.


Levels of dopamine (DA) in the different brain regions of the mouse after formula administration. Data are represented as mean±S.E.M. Groups of 7–8 mice received either a control condition (BAL), acute tryptophan depletion (ATD), or simplified acute tryptophan depletion (SATD) mixtures. HPC: hippocampus; FC: frontal cortex; Amyg: amygdala; CPu: caudate putamen; NAcc: nucleus accumbens.
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Figure 0006: Levels of dopamine (DA) in the different brain regions of the mouse after formula administration. Data are represented as mean±S.E.M. Groups of 7–8 mice received either a control condition (BAL), acute tryptophan depletion (ATD), or simplified acute tryptophan depletion (SATD) mixtures. HPC: hippocampus; FC: frontal cortex; Amyg: amygdala; CPu: caudate putamen; NAcc: nucleus accumbens.

Mentions: There was no main effect of treatment on brain TYR, DA, or DOPAC (F[2,109]=2.78, p=0.087; F[2,106]=2.06, p=0.154; F[2,106]=0.24, p=0.788, respectively, Figs. 5 and 6). However, a global ANOVA indicated an effect of region in both analytes (TYR: F[4,109]=31.64, p<0.0001; DA: F[4,108]=518.73, p<0.0001; DOPAC: F[4,108]=302.21, p<0.0001). A lower-order ANOVA and Fisher's post-hoc tests indicated that the dopaminergic metabolite DOPAC in the amygdala of SATD-treated mice was significantly higher relative to BAL-treated mice (F[2,21]=4.91, p=0.020). HVA showed a significant effect of treatment, region and treatment×region (Treatment: F[2,107]=6.29, p=0.008; region: F[4,107]=1349.35, p<0.0001; treatment×region: F[8,107]=7.23, p<0.001). The levels of HVA were affected (25–35% depletion, Table 3) in hippocampus, caudate, and nucleus accumbens when SATD was administered. ATD administration reduced HVA content in hippocampus and caudate (Fig. 7).


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

Sánchez CL, Van Swearingen AE, Arrant AE, Biskup CS, Kuhn CM, Zepf FD - Food Nutr Res (2015)

Levels of dopamine (DA) in the different brain regions of the mouse after formula administration. Data are represented as mean±S.E.M. Groups of 7–8 mice received either a control condition (BAL), acute tryptophan depletion (ATD), or simplified acute tryptophan depletion (SATD) mixtures. HPC: hippocampus; FC: frontal cortex; Amyg: amygdala; CPu: caudate putamen; NAcc: nucleus accumbens.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4538305&req=5

Figure 0006: Levels of dopamine (DA) in the different brain regions of the mouse after formula administration. Data are represented as mean±S.E.M. Groups of 7–8 mice received either a control condition (BAL), acute tryptophan depletion (ATD), or simplified acute tryptophan depletion (SATD) mixtures. HPC: hippocampus; FC: frontal cortex; Amyg: amygdala; CPu: caudate putamen; NAcc: nucleus accumbens.
Mentions: There was no main effect of treatment on brain TYR, DA, or DOPAC (F[2,109]=2.78, p=0.087; F[2,106]=2.06, p=0.154; F[2,106]=0.24, p=0.788, respectively, Figs. 5 and 6). However, a global ANOVA indicated an effect of region in both analytes (TYR: F[4,109]=31.64, p<0.0001; DA: F[4,108]=518.73, p<0.0001; DOPAC: F[4,108]=302.21, p<0.0001). A lower-order ANOVA and Fisher's post-hoc tests indicated that the dopaminergic metabolite DOPAC in the amygdala of SATD-treated mice was significantly higher relative to BAL-treated mice (F[2,21]=4.91, p=0.020). HVA showed a significant effect of treatment, region and treatment×region (Treatment: F[2,107]=6.29, p=0.008; region: F[4,107]=1349.35, p<0.0001; treatment×region: F[8,107]=7.23, p<0.001). The levels of HVA were affected (25–35% depletion, Table 3) in hippocampus, caudate, and nucleus accumbens when SATD was administered. ATD administration reduced HVA content in hippocampus and caudate (Fig. 7).

Bottom Line: Both 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.

View Article: PubMed Central - PubMed

Affiliation: Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, JARA Brain, RWTH Aachen University, Aachen, Germany.

ABSTRACT

Background: Diet 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.

Objective: The 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).

Design: The 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).

Results: Both 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.

Conclusion: A 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.

No MeSH data available.