Hippocampal metabolism of amino acids by L-amino acid oxidase is involved in fear learning and memory

Amino acids participate directly and indirectly in many important biochemical functions in the brain. We focused on one amino acid metabolic enzyme, L-amino acid oxidase (LAO), and investigated the importance of LAO in brain function using LAO1 knockout (KO) mice. Compared to wild-type mice, LAO1 KO mice exhibited impaired fear learning and memory function in a passive avoidance test. This impairment in LAO1 KO mice coincided with significantly reduced hippocampal acetylcholine levels compared to wild-type mice, while treatment with donepezil, a reversible acetylcholine esterase inhibitor, inhibited this reduction. Metabolomic analysis revealed that knocking out LAO1 affected amino acid metabolism (mainly of phenylalanine [Phe]) in the hippocampus. Specifically, Phe levels were elevated in LAO1 KO mice, while phenylpyruvic acid (metabolite of Phe produced largely by LAO) levels were reduced. Moreover, knocking out LAO1 decreased hippocampal mRNA levels of pyruvate kinase, the enzymatic activity of which is known to be inhibited by Phe. Based on our findings, we propose that LAO1 KO mice exhibited impaired fear learning and memory owing to low hippocampal acetylcholine levels. Furthermore, we speculate that hippocampal Phe metabolism is an important physiological mechanism related to glycolysis and may underlie cognitive impairments, including those observed in Alzheimer’s disease

STUDIES OF SEPARATION BEHAVIOR AND MECHANISM OF PLASTICS, PVC AND PET, BY FLOTATION METHOD

Heretofore, waste disposal by combustion or reclamation treatment has been prevalent. Since plastic is a very convenient material, the amount of waste plastic has been increasing without establishment of a particular recycling method for it.Recycling not only decreases wastes, but protects our environment, too. PVC (polyvinyl chloride) especially generates terrible toxic gases such as dioxin, chlorine and hydrochloride during the combustion process. As both PVC and PET (polyethylene terephthalate) have similar chemical and physical properties(hydrophobicity, specific gravity, etc), it is very difficult to separate them

ROC curve shows the single genus model and genera combination model.

Bifidobacterium and Megasphaera predict vendor A. Phascolarctobacterium and Prevotella predict vendor B. Megamonas, Bacteroides and Ruminococcus predict vendor C. (TIF)</p

Intra-individual (daily fluctuation) fecal microbiome similarity (%) based on ASV level.

(A) Comparison among animals supplied from three vendors by Kruskall-Walis test. (B) Comparison among animals grouped at age by Mann-Whitney test. The black lines show means, with the dot showing each animal’s intra-individual fecal microbiome similarity. (TIF)</p

Fecal microbiome differences among vendors.

(A) PCoA plot based on the Bray-Curtis dissimilarity index using ASV data of 316 samples from healthy marmosets. The points are colored by animal ID, and each eclipse shows each vendor. The PERMANOVA test was conducted when grouped by individuals and vendors. F-value: 48.886, 44.511; R-squared: 0.70967, 0.22144; both had a p-value of <0.001. (B) Box plots showing a comparison of alpha diversity calculated based on Chao1 and Shannon indices among vendors. The box extends from the 25th to 75th percentiles, and the line of middle of the box shows the median. The ends of the whiskers represent the smallest and largest values. The Kruskal-Wallis test was conducted for each comparison; p-value: ****, <0.0001. ***, <0.001. (C) Dendrogram constructed with first and last fecal microbiome over experimental period by ward methods, based on the Bray-Curtis dissimilarity index.</p

Relative abundance and prevalence of bacterial features shared in healthy female marmosets.

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List of anovulatory individuals.

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Comparison of fecal microbiome between normal and anovulatory estrous groups.

(A) Results of the LEfSe comparison between normal estrous group (NE) and anovulatory estrous group (AE) divided by vendors or individual marmosets. Color bar scale shows LDA sore; red means AE abundance, and blue means NE abundance; p-value: ***, Megamonas and Desulfovibrio between NE and AE. The box extends from the 25th to 75th percentiles, and the line in the middle of the box shows the median. The ends of the whiskers represent the smallest and largest values. Kruskal-Wallis test, p-value: ****, Megamonas, Desulfovibrio, and a combination of Megamonas and Desulfovibrio.</p