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This study aimed to investigate and determine the best deep learning (DL) model to predict breast cancer (BC) with dedicated breast positron emission tomography (dbPET) images.Of the 1598 women who underwent dbPET examination between April 2015 and August 2020, a total of 618 breasts on 309 examinations for 284 women who were diagnosed with BC or non-BC were analyzed in this retrospective study. The Xception-based DL model was trained to predict BC or non-BC using dbPET images from 458 breasts of 109 BCs and 349 non-BCs, which consisted of mediallateral and craniocaudal maximum intensity projection images, respectively. It was tested using dbPET images from 160 breasts of 43 BC and 117 non-BC. Two expert radiologists and two radiology residents also interpreted them. Sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were calculated.Our DL model had a sensitivity and specificity of 93% and 93%, respectively, while radiologists had a sensitivity and specificity of 77-89% and 79-100%, respectively. Diagnostic performance of our model (AUC = 0.937) tended to be superior to that of residents (AUC = 0.876 and 0.868, p = 0.073 and 0.073), although not significantly different. Moreover, no significant differences were found between the model and experts (AUC = 0.983 and 0.941, p = 0.095 and 0.907).Our DL model could be applied to dbPET and achieve the same diagnostic ability as that of experts.

We investigated the effects of fermented rice bran (FRB) administration in two groups of C57BL/6J mice. The first group was fed with a high-fat diet, and the second group was fed with a high-fat diet supplemented with the FRB for 8 weeks. FRB supplementation suppressed the high-fat-induced weight gain and considerable alterations in the intestinal microbiota profile in the second group. Among 27 bacterial genera detected in the FRB, only

The effect of Lactobacillus plantarum SNK12 (CPLP) supplementation on mRNA levels of hippocampal neurotrophic factors and gamma aminobutyric acid receptors (GABAR) was tested. In Experiment 1, stress-free, unsupplemented and CPLP (4 × 108 cells/head)-supplemented male C57BL/6J (B6) mice were the experimental animals. In Experiment 2, intruder (male, B6) mice [negative control; unsupplemented, sub-chronic mild social defeat stress (sCSDS)-induced; and CPLP-supplemented, sCSDS-induced] were exposed to aggressor mice (adult male Slc:ICR). mRNA levels of neurotrophic factors and GABAR in hippocampal samples of these mice were analyzed. In CPLP-supplemented mice of both experiments, mRNA levels of bdnf, nt-3, and GABAR were upregulated. Moreover, a tendency toward the improvement of habituation ability (Experiment 1) and behavior (Experiment 2) was observed in mice, which may be associated with upregulated neurotrophic factors and GABAR. We demonstrated that oral supplementation of CPLP to stress-free and stress-induced mice upregulated mRNA levels of hippocampal neurotrophic factors and GABAR.

A 71-year-old man was hospitalized because of low back pain and weakness in both lower limbs. He presented with fever and stiff neck, and his cerebrospinal fluid sample contained blood. MRI revealed intramedullary and epidural hemorrhages in the spinal cord. Microhemorrhages occurred frequently in the central nervous system over a short period. A brain biopsy was performed. The diagnosis was primary lymphomatoid granulomatosis (LYG) of the central nervous system (grade 2). As a result of lymphocytic infiltration to the vascular walls in LYG, hemorrhages occurred in multiple sites in the central nervous system. The biopsy of samples from the sites of microhemorrhages proved useful for diagnosis even in the absence of mass lesions.

The gut microbiota is involved in the pathogenesis of stress-related disorders. Probiotics can benefit the central nervous system via the microbiota–gut–brain axis, which raises the possibility that probiotics are effective in managing depression. In the present study, we examined the effects of heat-killed Lactobacillus helveticus strain MCC1848 in subchronic and mild social defeat stress (sCSDS) model mice (a widely used animal model of depression). MCC1848 supplementation significantly enhanced the interaction time in the social interaction test and sucrose preference ratio in the sucrose preference test, suggesting that MCC1848 improved anxiety- or depressive-like behaviors in sCSDS mice. The gene expression profile analysis of the nucleus accumbens, which plays an important role in stress resilience, indicated that MCC1848 ameliorated sCSDS-induced gene expression alterations in signal transduction or nervous system development. These findings suggest that MCC1848 supplementation is useful as a preventive strategy for chronic-stress-induced depression. Overview of anti-anxiety or depressant-like effects of heat-killed L. helevticus MCC1848.

Background Periodontopathic bacteria such as Porphyromonas gingivalis produce several metabolites, including lipopolysaccharide (LPS) and n-butyric acid (BA). Past work suggested that periodontal infection may cause cognitive impairment in mice. Aims To elucidate the mechanisms by which metabolites such as LPS and BA, resulting from Porphyromonas gingivalis activity, induce immunological and physiological abnormalities in mice. Methods In the present work, 28 male ICR mice were placed in an open-field arena and the total distance (cm/600 s) they covered was recorded. Based on their moving distances, mice were divided into 4 groups (n = 7) and injected the following substances into their gingival tissues for 32 consecutive days: saline (C), 5 mmol/L of BA (B), 1 μg/mouse of LPS (L), and BA-LPS (BL) solutions. Distances covered by mice were also measured on days 14 and 21, with their habituation scores considered as “(moving distance on day 14 or 21)/(moving distance on day 0)”. Afterwards, mice were dissected, and hippocampal gene expression and the concentrations of short-chain fatty acids, neurotransmitters and cytokines in their blood plasma and brains were analyzed. In addition, mouse brain and liver tissues were fixed and visually assessed for histopathological abnormalities. Results Group BL had significantly higher habituation scores than C and B on day 14. LPS induced higher habituation scores on day 21. LPS induced significant decreases in the mRNA levels of interleukin (IL)-6 and brain-derived neurotrophic factors, and an increase in neurotrophic tyrosine kinase receptor type 2. In both plasma and brain, LPS induced a significant acetate increase. Moreover, LPS significantly increased acetylcholine in brain. In plasma alone, LPS and BA significantly decreased monocyte chemoattractant protein 1 (MCP-1). However, while LPS significantly decreased tyrosine, BA significantly increased it. Lastly, LPS significantly decreased IL-6 and tumor necrosis factor in plasma. No histopathological abnormalities were detected in liver or brain tissues of mice. Conclusion We showed that injections of LPS and/or BA induced mice to move seemingly tireless and that both LPS and BA injections strongly induced a reduction of MCP-1 in blood plasma. We concluded that LPS and BA may have been crucial to induce and/or aggravate abnormal behavior in mice.

The intestinal ecosystem is involved in the pathogenesis of mood disorders such as depression. Intestinal microbes can affect the central nervous system through the gut-brain axis, which raises the possibility of using probiotics for preventing depression. In this study, we examined the effect of heat-inactivated Lactobacillus gasseri CP2305 (CP2305) in a subchronic and mild social defeat stress (sCSDS) mouse model. sCSDS suppressed food intake. However, dietary CP2305 intake rescued it, suggesting that CP2305 improved the decreased appetite in sCSDS mice. sCSDS did not alter the gene expression of brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 in the hippocampus. However, dietary CP2305 provided following sCSDS increased the gene expression of these neurotrophins in the hippocampus. These findings suggest that CP2305 supplementation would aid in preventing psychosocial stress-induced disorders.

Recently, it has been found that the gut microbiota influences functions of the host brain by affecting monoamine metabolism. The present study focused on the relationship between the gut microbiota and the brain amino acids. Specific pathogen-free (SPF) and germ-free (GF) mice were used as experimental models. Plasma and brain regions were sampled from mice at 7 and 16 weeks of age, and analysed for free d- and l-amino acids, which are believed to affect many physiological functions. At 7 weeks of age, plasma concentrations of d-aspartic acid (d-Asp), l-alanine (l-Ala), l-glutamine (l-Gln) and taurine were higher in SPF mice than in GF mice, but no differences were found at 16 weeks of age. Similar patterns were observed for the concentrations of l-Asp in striatum, cerebral cortex and hippocampus, and l-arginine (l-Arg), l-Ala and l-valine (l-Val) in striatum. In addition, the concentrations of l-Asp, d-Ala, l-histidine, l-isoleucine (l-Ile), l-leucine (l-Leu), l-phenylalanine and l-Val were significantly higher in plasma of SPF mice when compared with those of GF mice. The concentrations of l-Arg, l-Gln, l-Ile and l-Leu were significantly higher in SPF than in GF mice, but those of d-Asp, d-serine and l-serine were higher in some brain regions of GF mice than in those of SPF mice. In conclusion, the concentration of amino acids in the host brain seems to be dependent on presence of the gut microbiota. Amino acid metabolism in the host brain may be modified by manipulating microbiota communities.

The gut microbiota is involved in the pathogenesis of stress-related disorders. Probiotics can benefit the central nervous system via the microbiota-gut-brain axis, which raises the possibility that probiotics are effective in managing depression. In the present study, we examined the effects of heat-killed

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.

Dried bonito dashi, a traditional Japanese fish stock, enhances palatability of various dishes because of its specific flavor. Daily intake of dashi has also been shown to improve mood status such as tension-anxiety in humans. This study aimed at investigating beneficial effects of dashi ingestion on anxiety/depression-like behaviors and changes in amino acid levels in the brain and plasma in rats. Male Wistar rats were given either dried bonito dashi or water for long-term (29 days; Experiment 1) or single oral administration (Experiment 2). Anxiety and depression-like behaviors were tested using the open field and forced swimming tests, respectively. Concentrations of amino acids were measured in the hippocampus, hypothalamus, cerebellum, and jugular vein. During the long-term (29 days) consumption, rats given 2% dashi frequently entered the center zone and spent more time compared with the water controls in the open field test. However, the dashi was ineffective on depression-like behavior. In the hippocampus, concentrations of hydroxyproline, anserine, and valine were increased by dashi while those of asparagine and phenylalanine were decreased. In the hypothalamus, the methionine concentration was decreased. In a single oral administration experiment, the dashi (1%, 2% or 10%) showed no effects on behaviors. Significance was observed only in the concentrations of α-aminoadipic acid, cystathionine, and ornithine in the hippocampus. Dried bonito dashi is a functional food having anxiolytic-like effects. Daily ingestion of the dashi, even at lower concentrations found in the cuisine, reduces anxiety and alters amino acid levels in the brain.

Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood.

Interferon-induced transmembrane protein 3 (IFITM3) iplays a crucial role in the antiviral responses of Type I interferons (IFNs). The role of IFITM3 in the central nervous system (CNS) is, however, largely unknown, despite the fact that its expression is increased in the brains of patients with neurologic and neuropsychiatric diseases. Here, we show the role of IFITM3 in long-lasting neuronal impairments in mice following polyriboinosinic-polyribocytidylic acid (polyI:C, a synthetic double-stranded RNA)-induced immune challenge during the early stages of development. We found that the induction of IFITM3 expression in the brain of mice treated with polyI:C was observed only in astrocytes. Cultured astrocytes were activated by polyI:C treatment, leading to an increase in the mRNA levels of inflammatory cytokines as well as Ifitm3. When cultured neurons were treated with the conditioned medium of polyI:C-treated astrocytes (polyI:C-ACM), neurite development was impaired. These polyI:C-ACM-induced neurodevelopmental abnormalities were alleviated by ifitm3(-/-) astrocyte-conditioned medium. Furthermore, decreases of MAP2 expression, spine density, and dendrite complexity in the frontal cortex as well as memory impairment were evident in polyI:C-treated wild-type mice, but such neuronal impairments were not observed in ifitm3(-) (/) (-) mice. We also found that IFITM3 proteins were localized to the early endosomes of astrocytes following polyI:C treatment and reduced endocytic activity. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of development has non-cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes.

We previously reported that Wistar Kyoto rats, an animal model of depression, have a characteristically abnormal serine metabolism in the brain, i.e., lower serine and cystathionine, which is a metabolite of serine, concentrations in the brain. To explore the mechanism underlying this abnormality, the expression of cystathionine β-synthase and serine racemase, which are the enzymes involved in the serine metabolism, was investigated in the cerebellum and hippocampus of Wistar and Wistar Kyoto rats. Wistar Kyoto rats exhibited a significantly lower mRNA expression of cystathionine β-synthase in the cerebellum in comparison with Wistar rats, while expression levels in the hippocampus did not differ between strains. Previous study indicated that the reduction of cystathionine β-synthase in the brain induced cerebellar aplasia in mice. Therefore, the cerebellar size was compared between Wistar rats and Wistar Kyoto rats. Wistar Kyoto rats displayed a lower ratio of cerebellum weight to whole-brain weight compared with Wistar rats of the same generation or similar body weight, suggesting that Wistar Kyoto rats exhibit smaller cerebellum. These results suggest that the lower mRNA expression of cystathionine β-synthase in the cerebellum and the smaller size of cerebellum may be related to the depression-like behavior in Wistar Kyoto rats.

Djungarian hamster (P. sungorus) and Roborovskii hamster (P. roborovskii) belong to the same genus of phodopus. Roborovskii hamster shows high locomotor activity and low level of dopamine (DA) in the brain. Administration of L-tyrosine, a precursor of DA, decreases locomotor activity in Roborovskii hamsters. However, the amino acid metabolism in relation to the hyperactivity is not yet well known. In the present study, L- and D-amino acid concentrations in the brain, liver, and plasma in Djungarian and Roborovskii hamsters were investigated during day and night times to explain the possible difference in hyperactivity between them. Most of the examined amino acids were higher in the night time when hamsters are active compared to those in day time. L- and D-tyrosine concentrations were higher in the liver of Roborovskii hamsters than in Djungarian hamsters. Furthermore, brain concentration of D-tyrosine was higher in the Roborovskii than in Djungarian hamsters, but no significant difference was observed for L-tyrosine concentrations between the two species. These results suggest that the conversion of L-tyrosine to D-tyrosine in the brain of Roborovskii hamster may be higher than in Djungarian hamster, which may cause low DA concentration and hyperactivity in Roborovskii hamster. On the other hand, L- and D-serine, which are known as sedative factors, were lower in Roborovskii hamsters than Djungarian hamster. These results suggest that species-specific regulation in amino acid metabolism may contribute to hyperactivity in Roborovskii hamsters.

Interferon‐induced transmembrane protein 3 (IFITM3) ıplays a crucial role in the antiviral responses of Type I interferons (IFNs). The role of IFITM3 in the central nervous system (CNS) is, however, largely unknown, despite the fact that its expression is increased in the brains of patients with neurologic and neuropsychiatric diseases. Here, we show the role of IFITM3 in long‐lasting neuronal impairments in mice following polyriboinosinic‐polyribocytidylic acid (polyI:C, a synthetic double‐stranded RNA)‐induced immune challenge during the early stages of development. We found that the induction of IFITM3 expression in the brain of mice treated with polyI:C was observed only in astrocytes. Cultured astrocytes were activated by polyI:C treatment, leading to an increase in the mRNA levels of inflammatory cytokines as well as Ifitm3. When cultured neurons were treated with the conditioned medium of polyI:C‐treated astrocytes (polyI:C‐ACM), neurite development was impaired. These polyI:C‐ACM‐induced neurodevelopmental abnormalities were alleviated by ifitm3−/− astrocyte‐conditioned medium. Furthermore, decreases of MAP2 expression, spine density, and dendrite complexity in the frontal cortex as well as memory impairment were evident in polyI:C‐treated wild‐type mice, but such neuronal impairments were not observed in ifitm3−/− mice. We also found that IFITM3 proteins were localized to the early endosomes of astrocytes following polyI:C treatment and reduced endocytic activity. These findings suggest that the induction of IFITM3 expression in astrocytes by the activation of the innate immune system during the early stages of development has non‐cell autonomous effects that affect subsequent neurodevelopment, leading to neuropathological impairments and brain dysfunction, by impairing endocytosis in astrocytes. GLIA 2013