Improved cognition, mild anxiety-like behavior and decreased motor performance in pyridoxal phosphatase-deficient mice
Jeanclos E., Albersen M., Ramos R. J. J., Raab A., Wilhelm C., Hommers L., Lesh K. Yu., Verhoeven-Duif N. M., Gohla A.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Vol.1865, Issue1, P. 193-205
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1016/j.bbadis.2018.08.018
Аннотация:
Pyridoxal 5′-phosphate (PLP) is an essential cofactor in the catalysis of ~140 different enzymatic reactions. A pharmacological elevation of cellular PLP concentrations is of interest in neuropsychiatric diseases, but whole-body consequences of higher intracellular PLP levels are unknown. To address this question, we have generated mice allowing a conditional ablation of the PLP phosphatase PDXP. Ubiquitous PDXP deletion increased PLP levels in brain, skeletal muscle and red blood cells up to 3-fold compared to control mice, demonstrating that PDXP acts as a major regulator of cellular PLP concentrations in vivo. Neurotransmitter analysis revealed that the concentrations of dopamine, serotonin, epinephrine and glutamate were unchanged in the brains of PDXP knockout mice. However, the levels of γ-aminobutyric acid (GABA) increased by ~20[%], demonstrating that elevated PLP levels can drive additional GABA production. Behavioral phenotyping of PDXP knockout mice revealed improved spatial l
Ключевые слова:
Motor performance; Neuropsychiatric diseases; Neurotransmitter biosynthesis; Pyridoxal phosphatase; Vitamin B6; γ-Aminobutyric acid (GABA)
4 aminobutyric acid; dopamine; epinephrine; glutamic acid; neomycin; pyridoxal 5 phosphate; serotonin; agents interacting with transmitter, hormone or drug receptors; Pdxp protein, mouse; phosphatase; pyridoxal 5 phosphate; pyridoxine; 4 aminobutyric acid brain level; agar gel electrophoresis; amino acid metabolism; animal cell; animal experiment; animal tissue; anxiety; Article; biceps femoris muscle; biosynthesis; body weight; brain; brain circulus arteriosus; brain cortex; brain region; breeding; cerebellum; cervical spine dislocation; cognition; erythrocyte; escape latency; exploratory behavior; gene deletion; gene targeting; genotype; glycogen muscle level; grip strength; high performance liquid chromatography; hind paw; homologous recombination; in vivo study; inverted screen test; knockout mouse; liquid chromatography-mass spectrometry; locomotion; memory; mesencephalon; motor dysfunction; motor performance; mouse; muscle weakness; nerve cell; nonhuman; phenotype; priority journ
Язык текста: Английский
ISSN: 0925-4439
Jeanclos E.
Albersen M.
Ramos R. J. J.
Raab A.
Wilhelm C.
Hommers L.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Verhoeven-Duif N. M.
Gohla A.
Йеанcлос Е.
Алберсен М.
Рамос Р. Й. Й.
Рааб А.
Wилхелм C.
Хоммерс Л.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Верхоевен-Дуиф Н. М.
Гохла А.
Improved cognition, mild anxiety-like behavior and decreased motor performance in pyridoxal phosphatase-deficient mice
Текст визуальный непосредственный
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Elsevier Science Publisher B.V.
Vol.1865, Issue1 P. 193-205
2019
Статья
Motor performance Neuropsychiatric diseases Neurotransmitter biosynthesis Pyridoxal phosphatase Vitamin B6 γ-Aminobutyric acid (GABA)
4 aminobutyric acid dopamine epinephrine glutamic acid neomycin pyridoxal 5 phosphate serotonin agents interacting with transmitter, hormone or drug receptors Pdxp protein, mouse phosphatase pyridoxal 5 phosphate pyridoxine 4 aminobutyric acid brain level agar gel electrophoresis amino acid metabolism animal cell animal experiment animal tissue anxiety Article biceps femoris muscle biosynthesis body weight brain brain circulus arteriosus brain cortex brain region breeding cerebellum cervical spine dislocation cognition erythrocyte escape latency exploratory behavior gene deletion gene targeting genotype glycogen muscle level grip strength high performance liquid chromatography hind paw homologous recombination in vivo study inverted screen test knockout mouse liquid chromatography-mass spectrometry locomotion memory mesencephalon motor dysfunction motor performance mouse muscle weakness nerve cell nonhuman phenotype priority journ
Pyridoxal 5′-phosphate (PLP) is an essential cofactor in the catalysis of ~140 different enzymatic reactions. A pharmacological elevation of cellular PLP concentrations is of interest in neuropsychiatric diseases, but whole-body consequences of higher intracellular PLP levels are unknown. To address this question, we have generated mice allowing a conditional ablation of the PLP phosphatase PDXP. Ubiquitous PDXP deletion increased PLP levels in brain, skeletal muscle and red blood cells up to 3-fold compared to control mice, demonstrating that PDXP acts as a major regulator of cellular PLP concentrations in vivo. Neurotransmitter analysis revealed that the concentrations of dopamine, serotonin, epinephrine and glutamate were unchanged in the brains of PDXP knockout mice. However, the levels of γ-aminobutyric acid (GABA) increased by ~20[%], demonstrating that elevated PLP levels can drive additional GABA production. Behavioral phenotyping of PDXP knockout mice revealed improved spatial l