Limits...
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 5-hydroxyindoleacetic acid (5-HIAA) 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. *p<0.05 compared with BAL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4538305&req=5

Figure 0004: Levels of 5-hydroxyindoleacetic acid (5-HIAA) 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. *p<0.05 compared with BAL.

Mentions: A significant decrease of brain TRP levels was shown after SATD and ATD administration (F[2,109]=13.98, p<0.001; F[4,109]=12.97, p<0.0001, for an effect of treatment and region, respectively). A global ANOVA showed a main effect of treatment, region, and treatment×region on brain 5-HT and its metabolite 5-HIAA (Treatment: F[2,108]=41.11, p<0.0001; F[2,108]=50.44, p<0.0001; region: F[4,108]=65.79, p<0.0001; F[4,108]=211.50, p<0.0001; treatment×region: F[8,108]=2.40, p=0.023; F[8,108]=20.23, p<0.0001, respectively). Fisher's post-hoc tests showed the reductions in the brain 5-HT and 5-HIAA contents of mice after dietary SATD or ATD treatment relative to control condition (see Figs. 2–4 for a summary). While brain 5-HT concentrations were reduced by 20–35% after dietary administration of both SATD and ATD (Table 3) when compared with BAL, 5-HIAA exhibited a significantly higher decline (around 40–55%, p<0.0001). Globally, dietary administration of the new SATD mixture caused greater 5-HT-related depletion magnitude when compared with the ATD Moja-De formula (Table 2).


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 5-hydroxyindoleacetic acid (5-HIAA) 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. *p<0.05 compared with BAL.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 0004: Levels of 5-hydroxyindoleacetic acid (5-HIAA) 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. *p<0.05 compared with BAL.
Mentions: A significant decrease of brain TRP levels was shown after SATD and ATD administration (F[2,109]=13.98, p<0.001; F[4,109]=12.97, p<0.0001, for an effect of treatment and region, respectively). A global ANOVA showed a main effect of treatment, region, and treatment×region on brain 5-HT and its metabolite 5-HIAA (Treatment: F[2,108]=41.11, p<0.0001; F[2,108]=50.44, p<0.0001; region: F[4,108]=65.79, p<0.0001; F[4,108]=211.50, p<0.0001; treatment×region: F[8,108]=2.40, p=0.023; F[8,108]=20.23, p<0.0001, respectively). Fisher's post-hoc tests showed the reductions in the brain 5-HT and 5-HIAA contents of mice after dietary SATD or ATD treatment relative to control condition (see Figs. 2–4 for a summary). While brain 5-HT concentrations were reduced by 20–35% after dietary administration of both SATD and ATD (Table 3) when compared with BAL, 5-HIAA exhibited a significantly higher decline (around 40–55%, p<0.0001). Globally, dietary administration of the new SATD mixture caused greater 5-HT-related depletion magnitude when compared with the ATD Moja-De formula (Table 2).

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.