ArticleThe international journal of neuropsychopharmacology2011
5-Hydroxytryptophan during critical postnatal period improves cognitive performances and promotes dendritic spine maturation in genetic mouse model of phenylketonuria.
Article in The international journal of neuropsychopharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Trial
- Article
- Serotonergic modulation of excitatory synapse development and plasticity.Molecules and cells · 2026Review
- Article
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Serotonin dysfunction in ADHD.Journal of neurodevelopmental disorders · 2025Review
- Early life psychosocial stress increases binge-like ethanol consumption and CSF1R inhibition prevents stress-induced alterations in microglia and brain macrophage population density.Brain, behavior, & immunity - health · 2025Article
- Transcriptome Profiling of Phenylalanine-Treated Human Neuronal Model: Spotlight on Neurite Impairment and Synaptic Connectivity.International journal of molecular sciences · 2024Article
- Serotonergic Modulation of the Excitation/Inhibition Balance in the Visual Cortex.International journal of molecular sciences · 2023Article
- Cognitive Functioning in Adults with Phenylketonuria in a Cohort of Spanish Patients.Behavioural neurology · 2023Article
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
- Role of age and neuroinflammation in the mechanism of cognitive deficits in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse.Brain sciences · 2020Article
- Psychiatric and Cognitive Aspects of Phenylketonuria: The Limitations of Diet and Promise of New Treatments.Frontiers in psychiatry · 2019Review
- Article
- AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria.Journal of inherited metabolic disease · 2018Article
- Maternal phenylketonuria syndrome: studies in mice suggest a potential approach to a continuing problem.Pediatric research · 2018Article
- Targeting mGlu5 Metabotropic Glutamate Receptors in the Treatment of Cognitive Dysfunction in a Mouse Model of Phenylketonuria.Frontiers in neuroscience · 2018Article
- Unbalance between Excitation and Inhibition in Phenylketonuria, a Genetic Metabolic Disease Associated with Autism.International journal of molecular sciences · 2017Article
- Early-onset behavioral and neurochemical deficits in the genetic mouse model of phenylketonuria.PloS one · 2017Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Although phenylketonuria (PKU) is the most common genetic cause of mental retardation, the cellular mechanisms underlying impaired brain function are still unclear. Using PAHenu2 mice (ENU2), the genetic mouse model of PKU, we previously demonstrated that high phenylalanine levels interfere with brain tryptophan hydroxylase activity by reducing the availability of serotonin (5-hydroxytryptamine, 5-HT), crucial for maturation of neuronal connectivity in the prefrontal cortex (PFC), around the third postnatal week, a critical period for cortical maturation. 5-Hydroxytryptophan (5-HTP), the product of tryptophan hydroxylation, is known to be a better treatment to increase brain 5-HT levels. In this study we investigated the role of 5-HT during the early postnatal period in cognitive disturbances and in cortical dendritic alterations of PKU subjects by restoring temporarily (postnatal days 14-21) physiological brain levels of 5-HT in ENU2 through 5-HTP treatment. In adult ENU2 mice early 5-HTP treatment reverses cognitive deficits in spatial and object recognition tests accompanied by an increase in spine maturation of pyramidal neurons in layer V of the prelimbic/infralimbic area of the PFC, although locomotor deficits are not recovered by treatment. Taken together, our results support the hypothesis that mental retardation in PKU depends on reduced availability of brain 5-HT during critical developmental periods that interferes with cortical maturation and point to 5-HTP supplementation as a highly promising additional tool to heal PKU patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.