Objective:To observe the relationship between hippocampal neuron injury in rats with phenylketonuria and the brain-derived growth factor(BDNF)/tyrosine kinase receptor B(TrkB) pathway, and to explore the possible mechanism of hippocampal neuron injury. Methods:Twenty-four rats were divided into control group and phenylketonuria group by random number method with 12 rats in each group. Urine test was conducted with 10%FeCl3 liquid chromogenic analysis. Tyrosine and phenylalanine levels in cerebral cortex and serum were determined by HPLC-fluorescence detection. Pathological changes in the CA1 region of the hippocampus were observed by HE staining. Levels of cysteine-containing aspartate proteolytic enzyme 3(Caspase-3), b-lymphocytoma-2(bcl-2), BDNF, TrkB, phosphorylated extracellular regulatory protein kinase(p-erk), and phosphorylated serine/threonine kinase(P-Akt) proteins in hippocampus were determined by Western blot. Results:The urine of rats in phenylketonuria group was strongly positive. The levels of phenylalanine in the cerebral cortex and serum in the phenylketonuria group were significantly higher than those of the control group(P<0.05), while the levels of phenylalanine in the cerebral cortex and serum in the phenylketonuria group were significantly lower than those of the control group(P<0.05). In phenylketonuria group, the tissue structure in CA1 area of the hippocampus was disordered, and the cell structure was fuzzy and disordered. The degeneration and necrosis of neurons were observed. The number of apoptic cells in the CA1 region of hippocampus in phenylketonuria group was higher than that of the control group(P<0.05). The levels of Caspase-3, Bcl-2, BDNF, TrkB, p-erk and p-akt protein in hippocampus of the phenylketonuria group were higher than those of the control group(P<0.05). Conclusion:The mechanism of hippocampal neurons injury in phenylketonuria rats may be related to the BDNF/TrkB pathway.
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