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      Plasma Brain-Derived Neurotrophic Factor and Reverse Dipping Pattern of Nocturnal Blood Pressure in Patients with Cardiovascular Risk Factors

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          Abstract

          Context

          Basic studies have shown that brain-derived neurotrophic factor (BDNF) has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.

          Objective

          We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers), and cardiac autonomic function as determined by heart rate variability (HRV).

          Design

          This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Study from October 2010 to November 2012.

          Patients

          Two-hundred fifty patients with 1 or more cardiovascular risk factor(s) (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease) were enrolled.

          Results

          Plasma BDNF levels (natural logarithm transformed) were significantly (p = 0.001) lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36) as compared to dippers (7.86±0.86 pg/ml, n = 100). Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228–0.762, P = 0.004) was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR) and frequency-domain (LF) of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.

          Conclusions

          Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function may be partly involved.

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          Most cited references30

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          Diagnosis and classification of diabetes mellitus.

          (2004)
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            BDNF mediates adaptive brain and body responses to energetic challenges.

            Emerging findings suggest that brain-derived neurotrophic factor (BDNF) serves widespread roles in regulating energy homeostasis by controlling patterns of feeding and physical activity, and by modulating glucose metabolism in peripheral tissues. BDNF mediates the beneficial effects of energetic challenges such as vigorous exercise and fasting on cognition, mood, cardiovascular function, and on peripheral metabolism. By stimulating glucose transport and mitochondrial biogenesis BDNF bolsters cellular bioenergetics and protects neurons against injury and disease. By acting in the brain and periphery, BDNF increases insulin sensitivity and parasympathetic tone. Genetic factors, a 'couch potato' lifestyle, and chronic stress impair BDNF signaling, and this may contribute to the pathogenesis of metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes, and neurological disorders. Published by Elsevier Ltd.
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              A de novo mutation affecting human TrkB associated with severe obesity and developmental delay.

              An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                25 August 2014
                : 9
                : 8
                : e105977
                Affiliations
                [1 ]Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
                [2 ]Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
                Rutgers University, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: HK YM TY MI. Performed the experiments: M. Kadoya AK M. Kurajoh MH JS HO TS. Analyzed the data: M. Kadoya HK. Contributed reagents/materials/analysis tools: M. Kadoya HK. Contributed to the writing of the manuscript: M. Kadoya HK MN.

                Article
                PONE-D-14-23522
                10.1371/journal.pone.0105977
                4143316
                25153796
                2de381ab-3dcb-4161-b1f4-e22cdfa13bb3
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 May 2014
                : 25 July 2014
                Page count
                Pages: 8
                Funding
                Grant-in-Aid for Scientific Research (26461371 to H.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. A Grant-in-Aid for Promotion of Technological Seeds in Advanced Medicine, Hyogo College of Medicine (to T.Y.). A Grant-in-Aid for Graduate Students, Hyogo College of Medicine (to M.K.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Nervous System
                Autonomic Nervous System
                Biochemistry
                Hormones
                Peptide Hormones
                Neuropeptides
                Neurochemistry
                Neurochemicals
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Hypertension
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

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