Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains

Zhang, Wynne Q.; Smolik, Corey M.; Barba-Escobedo, Priscilla A.; Gamez, Monica; Sanchez, Jesus J.; Javors, Martin A.; Daws, Lynette C.; Gould, Georgianna G.

doi:10.1016/j.neuropharm.2014.10.024

Cited by 51 publications

(48 citation statements)

References 86 publications

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“…Some indications present in literature suggest that B6 can differ from BTBR in their response to neurotransmitter manipulations. For instance, a comparison of acute tryptophan depletion, a method to deplete serotonin, both B6 and BTBR WT's show a decrease in serotonin but the tryptophan depletion only altered social interaction and social novelty behaviors in B6 and not in BTBR (Zhang et al, 2015). Furthermore, administration of the serotonin agonist 3-chlorophenylpiperazine (CCP) in WT B6 has not affected locomotor activity nor performance of the B6 in learning and memory paradigm (Vetulani et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background

Bruinenberg

Goot

Vliet

et al. 2016

Front. Behav. Neurosci.

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To unravel the role of gene mutations in the healthy and the diseased state, countless studies have tried to link genotype with phenotype. However, over the years, it became clear that the strain of mice can influence these results. Nevertheless, identical gene mutations in different strains are often still considered equals. An example of this, is the research done in phenylketonuria (PKU), an inheritable metabolic disorder. In this field, a PKU mouse model (either on a BTBR or C57Bl/6 background) is often used to examine underlying mechanisms of the disease and/or new treatment strategies. Both strains have a point mutation in the gene coding for the enzyme phenylalanine hydroxylase which causes toxic concentrations of the amino acid phenylalanine in blood and brain, as found in PKU patients. Although the mutation is identical and therefore assumed to equally affect physiology and behavior in both strains, no studies directly compared the two genetic backgrounds to test this assumption. Therefore, this study compared the BTBR and C57Bl/6 wild-type and PKU mice on PKU-relevant amino acid- and neurotransmitter-levels and at a behavioral level. The behavioral paradigms were selected from previous literature on the PKU mouse model and address four domains, namely (1) activity levels, (2) motor performance, (3) anxiety and/or depression-like behavior, and (4) learning and memory. The results of this study showed comparable biochemical changes in phenylalanine and neurotransmitter concentrations. In contrast, clear differences in behavioral outcome between the strains in all four above-mentioned domains were found, most notably in the learning and memory domain. The outcome in this domain seem to be primarily due to factors inherent to the genetic background of the mouse and much less by differences in PKU-specific biochemical parameters in blood and brain. The difference in behavioral outcome between PKU of both strains emphasizes that the consequence of the PAH mutation is influenced by other factors than Phe levels alone. Therefore, future research should consider these differences when choosing one of the genetic strains to investigate the pathophysiological mechanism underlying PKU-related behavior, especially when combined with new treatment strategies.

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Section: Discussionmentioning

confidence: 99%

The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background

Bruinenberg

Goot

Vliet

et al. 2016

Front. Behav. Neurosci.

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“…Normal patterns but unusually long bouts of self-grooming have been demonstrated in several mutant mouse models of autism, including Shank3 (Peca et al 2011), Cntnap2 (Penagarikano et al 2011), Neurexin1α (Etherton et al 2009), and Neuroligin1 (Blundell et al 2010). High levels of self-grooming have been well-replicated in the BTBR mouse model of idiopathic autism (Yang et al 2007; McFarlane et al 2008; Yang et al 2009; Pobbe et al 2010; Silverman et al 2010a; Amodeo et al 2012, 2014b; Zhang et al 2015), while the BALB inbred mouse line does not display repetitive self-grooming (Silverman et al 2010b). Recent work in transgenic rats reported perseverative chewing behavior in Fmr1 KO rats (Hamilton et al 2014).…”

Section: Mouse Behavioral Assays Relevant To the Diagnostic And Assmentioning

confidence: 97%

Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics

Kazdoba

Leach

Yang

et al. 2015

Current Topics in Behavioral Neurosciences

110

118

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Animal models provide preclinical tools to investigate the causal role of genetic mutations and environmental factors in the etiology of autism spectrum disorder (ASD). Knockout and humanized knock-in mice, and more recently knockout rats, have been generated for many of the de novo single gene mutations and copy number variants (CNVs) detected in ASD and comorbid neurodevelopmental disorders. Mouse models incorporating genetic and environmental manipulations have been employed for preclinical testing of hypothesis-driven pharmacological targets, to begin to develop treatments for the diagnostic and associated symptoms of autism. In this review, we summarize rodent behavioral assays relevant to the core features of autism, preclinical and clinical evaluations of pharmacological interventions, and strategies to improve the translational value of rodent models of autism.

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“…The BTBR inbred mouse strain, which shows many autism-relevant behavioral phenotypes, shows decreased baseline SERT binding throughout the brain and increased 5-HT 1A activity in the hippocampus (Gould et al, 2011, Gould et al, 2014). Further, short-term tryptophan supplementation as well as acute treatment with the serotonin reuptake inhibitor fluoxetine or the 5-HT 1A partial agonist buspirone result in increased sociability in BTBR mice (Chadman, 2011, Gould et al, 2011, Gould et al, 2014, Zhang et al, 2015). …”

Section: Mouse Models Of Asd Risk With Abnormal 5-htmentioning

confidence: 99%

The serotonin system in autism spectrum disorder: From biomarker to animal models

2016

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Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.

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Acute dietary tryptophan manipulation differentially alters social behavior, brain serotonin and plasma corticosterone in three inbred mouse strains

Cited by 51 publications

References 86 publications

The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background

The Behavioral Consequence of Phenylketonuria in Mice Depends on the Genetic Background

Translational Mouse Models of Autism: Advancing Toward Pharmacological Therapeutics

The serotonin system in autism spectrum disorder: From biomarker to animal models

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