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A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria

Molecular Neurobiology, University of Groningen, 9747 AG Groningen, The Netherlands
Division of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
Nutricia Research, Nutricia Advanced Medical Nutrition, 3584 CT Utrecht, The Netherlands
Authors to whom correspondence should be addressed.
Nutrients 2016, 8(4), 185;
Received: 26 November 2015 / Revised: 24 February 2016 / Accepted: 22 March 2016 / Published: 26 March 2016
(This article belongs to the Special Issue Nutrition in Cognitive Function)
The inherited metabolic disease phenylketonuria (PKU) is characterized by increased concentrations of phenylalanine in the blood and brain, and as a consequence neurotransmitter metabolism, white matter, and synapse functioning are affected. A specific nutrient combination (SNC) has been shown to improve synapse formation, morphology and function. This could become an interesting new nutritional approach for PKU. To assess whether treatment with SNC can affect synapses, we treated PKU mice with SNC or an isocaloric control diet and wild-type (WT) mice with an isocaloric control for 12 weeks, starting at postnatal day 31. Immunostaining for post-synaptic density protein 95 (PSD-95), a post-synaptic density marker, was carried out in the hippocampus, striatum and prefrontal cortex. Compared to WT mice on normal chow without SNC, PKU mice on the isocaloric control showed a significant reduction in PSD-95 expression in the hippocampus, specifically in the granular cell layer of the dentate gyrus, with a similar trend seen in the cornus ammonis 1 (CA1) and cornus ammonis 3 (CA3) pyramidal cell layer. No differences were found in the striatum or prefrontal cortex. PKU mice on a diet supplemented with SNC showed improved expression of PSD-95 in the hippocampus. This study gives the first indication that SNC supplementation has a positive effect on hippocampal synaptic deficits in PKU mice. View Full-Text
Keywords: synaptic proteins; Hippocampus; PSD-95; nutrient combination; phenylketonuria synaptic proteins; Hippocampus; PSD-95; nutrient combination; phenylketonuria
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Bruinenberg, V.M.; Van Vliet, D.; Attali, A.; De Wilde, M.C.; Kuhn, M.; Van Spronsen, F.J.; Van der Zee, E.A. A Specific Nutrient Combination Attenuates the Reduced Expression of PSD-95 in the Proximal Dendrites of Hippocampal Cell Body Layers in a Mouse Model of Phenylketonuria. Nutrients 2016, 8, 185.

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