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Aim: Overweight is associated with low-grade systemic inflammation. However, its effect on neuroinflammation remains unclear. We examined the possible association between overweight and neuroinflammation using cerebrospinal fluid (CSF) in a nonclinical adult population in Japan., Methods: CSF and plasma levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), plasma levels of C-reactive protein (CRP), and leptin were measured in nonclinical adult participants (35 males and 34 females) who had no current or past history of neuropsychiatric diseases. We performed partial correlation analyses with sex and age as covariates between the body mass index (BMI) and the inflammatory markers and compared them between overweight and nonoverweight participants., Results: The BMI significantly correlated with CSF levels of IL-6 (rs = 0.32, p = 0.009), plasma levels of CRP (rs = 0.30, p = 0.016), IL-1β (rs = 0.29, p = 0.019), IL-6 (rs = 0.25, p = 0.042), TNF-α (rs = 0.43, p < 0.001), and leptin (rs = 0.72, p < 0.001). Overweight participants (BMI ≧ 25) had significantly higher CSF levels of IL-6 (p < 0.001), plasma levels of IL-1β (p = 0.023), TNF-α (p < 0.001), and leptin (p < 0.001) than the nonoverweight participants., Conclusion: Overweight is associated with central IL-6, a marker for neuroinflammation, as well as systemic inflammation markers, even in a nonclinical population., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Elevated levels of glial fibrillary acidic protein (GFAP) in plasma reflect neuroinflammation and are linked to cognitive decline. Preclinical studies show that dietary change can attenuate astrocyte reactivity and neuroinflammation. In the current study, we investigate if the Okinawa-based Nordic (O-BN) diet alters plasma GFAP levels in patients with Type 2 Diabetes (T2D), a metabolic disorder associated with cognitive disturbances and an increased risk of dementia. Plasma GFAP levels were measured in T2D patients (n = 30) at baseline, after 3 months of the diet, and after a subsequent 4 months of unrestricted diets. The GFAP levels decreased significantly after 3 months of the diet ( p = 0.048) but reverted to baseline levels after 4 months of unrestricted diets. At baseline, the GFAP levels correlated significantly with levels of the neurodegeneration marker neurofilament light polypeptide (r = 0.400*) and, after correcting for age, sex, and body mass index, with proinflammatory plasma cytokines (ranging from r = 0.440* to r = 0.530**) and the metabolic hormone islet amyloid polypeptide (r = 0.478*). We found no correlation with psychological well-being. These results suggest that the O-BN diet reduces neuroinflammation in T2D patients and may thus be an important preventive measure for managing T2D and reducing the risk of neurodegenerative disorders.

Rationale: As a species, humans are vulnerable to numerous mental disorders, including depression and schizophrenia. This susceptibility may be due to the evolution of our large, complex brains, or perhaps because these illnesses counterintuitively confer some adaptive advantage. Additionally, cultural and biological factors may contribute to susceptibility and variation in mental illness experience and expression. Taking a holistic perspective could strengthen our understanding of these illnesses in diverse cultural contexts. Objectives: This paper reviews some of these potential factors and contextualizes mental disorders within a biocultural framework. Results: There is growing evidence that suggests cultural norms may influence inflammation, neurotransmitters, and neurobiology, as well as the illness experience. Specific examples include variation in schizophrenia delusions between countries, differences in links between inflammation and emotion between the United States and Japan, and differences in brain activity between Caucasian and Asian participants indicating that cultural values may moderate cognitive processes related to social cognition and interoception. Conclusions: Research agendas that are grounded in an appreciation of biocultural diversity as it relates to psychiatric illness represent key areas for truly interdisciplinary research that can result in culturally sensitive treatments and highlight possible biological variation affecting medical treatment. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most devastating age-related neurodegenerative diseases after Alzheimer diseases (AD) and is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN) and aggregation of α-synuclein (α-syn). The precise etiology of PD is not yet fully understood and lacks the disease-modifying therapeutic strategies that could reverse the ongoing neurodegeneration. In the quest of exploring novel disease modifying therapeutic strategies, natural compounds from plant sources have gained much attention in recent days. Glycyrrhizin (GL) is the main active ingredient of the roots and rhizomes of licorice (Glycyrrhiza glabra L), which are generally used in the treatment of inflammatory diseases or as a tonifying herbal medicine. In Persia, GL is a conventional neuroprotective agent that are used to treat neurological disorders. The traditional use of GL in Japan is to treat chronic hepatitis B. In addition, GL is a natural inhibitor of high mobility group box 1 (HMGB1) which has exerted neuroprotective effect against several HMGB1 mediated pathological conditions. The study is aimed to evaluate therapeutic effect of GL against PD in zebrafish. PD in zebrafish larvae is induced by administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Apoptosis was assessed with TUNEL assay. Gene expression was performed to assess the modulation in genes related to neuroinflammatory and autophagy. We observed that GL co-treatment increased the length of DA neurons, decreased the number of apoptotic cells in zebrafish brain, and inhibited the loss of vasculature and disorganized vasculature induced by MPTP. GL co-treatment relieved the MPTP-induced locomotor impairment in zebrafish. GL co-treatment suppressed MPTP-induced upregulated mRNA expression of inflammatory markers such as hmgb1a , tlr4b, nfκb, il1β , and il6. GL co-treatment suppressed the autophagy related genes α-syn and atg5 whereas increased the mRNA expression level of parkin and pink1. In addition, molecular docking study reveals that GL has binding interaction with HMGB1, TLR4, and RAGE. Hence, the effect of GL co-treatment on MPTP-induced PD-like condition in zebrafish is to alleviate apoptosis and autophagy, as well as suppress inflammatory responses. [Display omitted] • GL co-treatment ameliorates MPTP-induced PD like condition in zebrafish. • GL anti-PD effect might be mediated by its regulation in inflammation and autophagy. • Molecular docking reveals the interaction of GL with HMGB1, TLR4, and RAGE. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a disease of the central nervous system that progressively affects the motor system. Epidemiological studies have provided evidence that exposure to agriculture-related occupations or agrichemicals elevate a person's risk for PD. Here, we sought to examine the possible epigenetic changes associated with working on a plantation on Oahu, HI and/or exposure to organochlorines (OGC) in PD cases., Results: We measured genome-wide DNA methylation using the Illumina Infinium HumanMethylation450K BeadChip array in matched peripheral blood and postmortem brain biospecimens in PD cases (n = 20) assessed for years of plantation work and presence of organochlorines in brain tissue. The comparison of 10+ to 0 years of plantation work exposure detected 7 and 123 differentially methylated loci (DML) in brain and blood DNA, respectively (p < 0.0001). The comparison of cases with 4+ to 0-2 detectable levels of OGCs, identified 8 and 18 DML in brain and blood DNA, respectively (p < 0.0001). Pathway analyses revealed links to key neurotoxic and neuropathologic pathways related to impaired immune and proinflammatory responses as well as impaired clearance of damaged proteins, as found in the predominantly glial cell population in these environmental exposure-related PD cases., Conclusions: These results suggest that distinct DNA methylation biomarker profiles related to environmental exposures in PD cases with previous exposure can be found in both brain and blood.

Chronic neuroinflammation is reported to be associated in the progression of many neurodegenerative diseases and there is an increasing interest for the natural products as neuroprotective and anti‐neuroinflammatory agents. In present research, we evaluated the potential inhibitory effects of extract, fractions, and isolated compounds from Citrus 'Hebesu' on lipopolysaccharide (LPS)‐induced inflammatory responses using BV‐2 murine microglial cells. The dried methanol extract (CH) was suspended in water and partitioned with hexane and ethyl acetate to give hexane soluble (CHH), ethyl acetate soluble (CHE), and water soluble (CHW) fractions. The extract (CH) and fractions CHH and CHE inhibited the expression of mRNA encoding pro‐inflammatory cytokine interleukin (IL)‐1β. CHE and CHH were further purified by various column chromatographic methods to obtain hesperidin (1), tangeretin (2), 5‐hydroxy‐6,7,8,3′,4′‐pentamethoxyflavone (3), 3,5,6,7,8,3′,4′‐heptamethoxyflavone (4), nobiletin (5), 3,4,5‐trimethoxy‐trans‐cinnamic alcohol (6), and meranzin hydrate (7). Among them, three polymethoxyflavonoids, 3, 4, and 5 significantly inhibited the expression of IL‐1β mRNA. Practical applications: Citrus 'Hebesu' is a local cultivar in Hyuga City, Miyazaki prefecture, Japan and its immature fruits are consumed with different food recipes. Till now, there is no detailed study on the chemical constituents and anti‐neuroinflammatory activity of this cultivar. In this study, seven compounds were isolated from the peels of immature fruits. Methanol extract, hexane, and ethyl acetate fractions and three polymethoxyflavonoids showed a significant inhibitory activity against expression of IL‐1β mRNA. Consumption of peels of Citrus 'Hebesu' might play important role in the prevention and treatment of neurodegenerative diseases, however, detailed mechanism based in vivo studies are necessary in future for providing more scientific evidences. [ABSTRACT FROM AUTHOR]

We herein report the case of a 14-year-old girl who had been experiencing chronic fatigue, febricula, and social withdrawal for 20 months. No notable abnormalities were identified during routine checkups at a general pediatric hospital; symptomatic treatments did not affect her condition. She was diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Based on the concepts of Japanese traditional medicine, she was administered shosaikoto-based treatment. After several weeks of treatment, all of the symptoms had been dramatically alleviated, consequently resolving the issue of non-attendance at school. Shosaikoto-based medication may be a therapeutic option for treating ME/CFS in patients presenting with chronic febricula.

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function., (Copyright © 2015 Elsevier Inc. All rights reserved.)