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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.


Serum levels of tryptophan (TRP), serotonin (5-HT), and tyrosine (TYR) in 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. *p<0.05 compared with BAL.
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Figure 0001: Serum levels of tryptophan (TRP), serotonin (5-HT), and tyrosine (TYR) in 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. *p<0.05 compared with BAL.

Mentions: The contents of the AAs TRP and TYR and the neurotransmitter 5-HT were measured in serum of male C57BL/6J mice treated with BAL, ATD, or SATD (Fig. 1). Animals treated with either ATD or SATD showed significantly decreased serum TRP content relative to controls (F[2,23]=6.85, p=0.005). However, no treatment effect of ATD or SATD on serum TYR was detected (F[2,23]=1.86, p=0.181). Circulating 5-HT concentrations were not significantly different between either SATD or ATD treatments versus BAL administration (F[2,23]=0.04, p=0.965).


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)

Serum levels of tryptophan (TRP), serotonin (5-HT), and tyrosine (TYR) in 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. *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 0001: Serum levels of tryptophan (TRP), serotonin (5-HT), and tyrosine (TYR) in 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. *p<0.05 compared with BAL.
Mentions: The contents of the AAs TRP and TYR and the neurotransmitter 5-HT were measured in serum of male C57BL/6J mice treated with BAL, ATD, or SATD (Fig. 1). Animals treated with either ATD or SATD showed significantly decreased serum TRP content relative to controls (F[2,23]=6.85, p=0.005). However, no treatment effect of ATD or SATD on serum TYR was detected (F[2,23]=1.86, p=0.181). Circulating 5-HT concentrations were not significantly different between either SATD or ATD treatments versus BAL administration (F[2,23]=0.04, p=0.965).

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.