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

被引:10
作者
Bruinenberg, Vibeke M. [1 ]
van Vliet, Danique [2 ]
Attali, Amos [3 ]
de Wilde, Martijn C. [3 ]
Kuhn, Mirjam [3 ]
van Spronsen, Francjan J. [2 ]
van der Zee, Eddy A. [1 ]
机构
[1] Univ Groningen, Mol Neurobiol, NL-9747 AG Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Div Metab Dis, NL-9713 GZ Groningen, Netherlands
[3] Nutricia Adv Med Nutr, Nutricia Res, NL-3584 CT Utrecht, Netherlands
关键词
synaptic proteins; Hippocampus; PSD-95; nutrient combination; phenylketonuria; SYNAPTIC-TRANSMISSION; DYSFUNCTION; PKU; DENSITY; BRAIN; MATURATION; PROTEINS; CHILDREN; OUTCOMES; SPINES;
D O I
10.3390/nu8040185
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
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.
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页数:8
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