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      Circulating Brain-Derived Neurotrophic Factor and Indices of Metabolic and Cardiovascular Health: Data from the Baltimore Longitudinal Study of Aging

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          Abstract

          Background

          Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile.

          Methodology/Principal Findings

          To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age ∼70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin.

          Conclusion/Significance

          Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined.

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          Most cited references42

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          Excess deaths associated with underweight, overweight, and obesity.

          Katherine Flegal (2005)
          As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. To estimate deaths associated with underweight (body mass index [BMI] or =30) in the United States in 2000. We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) I (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES III (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. Number of excess deaths in 2000 associated with given BMI levels. Relative to the normal weight category (BMI 18.5 to or =30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight with 33,746 excess deaths (95% CI, 15,726-51,766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161,223 to -10,966). The relative risks of mortality associated with obesity were lower in NHANES II and NHANES III than in NHANES I. Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease.
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            Homocysteine and cardiovascular disease.

            H Refsum, P Ueland, O Nygård … (1998)
            An elevated level of total homocysteine (tHcy) in blood, denoted hyperhomocysteinemia, is emerging as a prevalent and strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism. The basis for these conclusions is data from about 80 clinical and epidemiological studies including more than 10,000 patients. Elevated tHcy confers a graded risk with no threshold, is independent of but may enhance the effect of the conventional risk factors, and seems to be a particularly strong predictor of cardiovascular mortality. Hyperhomocysteinemia is attributed to commonly occurring genetic and acquired factors including deficiencies of folate and vitamin B12. Supplementation with B-vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce an elevated tHcy level. Studies are now in progress to establish whether such therapy will reduce cardiovascular risk.
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              The impact of age, weight and gender on BDNF levels in human platelets and plasma.

              Marek Lommatzsch, Doerte Zingler, Katharina Schuhbaeck … (2005)
              Brain-derived neurotrophic factor (BDNF) is a key mediator of neuronal plasticity in the adult. BDNF is known to be stored in human platelets and to circulate in plasma, but the regulation and function of BDNF in peripheral blood is still poorly understood. In this prospective study, we have examined 140 healthy, non-allergic adults (20-60 years old) to elucidate the impact of age and physical parameters on BDNF levels in human platelets and plasma. There was a wide concentration range of BDNF in serum (median: 22.6 ng/ml), platelets (median: 92.7 pg/10(6) platelets) and plasma (median: 92.5 pg/ml). BDNF levels in plasma decreased significantly with increasing age or weight, whereas platelet levels did not. When matched for weight, there were no significant gender differences regarding BDNF plasma levels. However, women displayed significantly lower platelet BDNF levels than men. In addition, platelet BDNF levels changed during the menstrual cycle. In conclusion, we demonstrate that parameters such as age or gender have a specific impact on stored and circulating BDNF levels in peripheral blood.
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                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2010
                Publication date (Electronic): 9 April 2010
                Volume: 5
                Issue: 4
                Electronic Location Identifier: e10099
                Affiliations
                [1 ]Cellular and Molecular Neurosciences Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America
                [2 ]Metabolism Unit, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America
                [3 ]Receptor Pharmacology Unit, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America
                [4 ]Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America
                [5 ]Diabetes Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America
                [6 ]Laboratory of Personality and Cognition, National Institute on Aging Intramural Research Program, Baltimore, Maryland, United States of America
                Sapienza University of Rome, Italy
                Author notes

                Conceived and designed the experiments: SRM LF BM MPM. Performed the experiments: EJG SRM BGW ODC BM. Analyzed the data: EJG SRM BGW ID BM. Contributed reagents/materials/analysis tools: SRM BGW ODC JME LF MPM. Wrote the paper: EJG AE SRM BM MPM.

                Article
                Publisher ID: 09-PONE-RA-13135R1
                DOI: 10.1371/journal.pone.0010099
                PMC ID: 2852401
                PubMed ID: 20404913
                SO-VID: 535359ab-3bca-44c1-9588-d225478f6dfb
                Copyright © This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
                History
                Date received : 24 September 2009
                Date accepted : 10 March 2010
                Page count
                Pages: 9
                Categories
                Subject: Research Article
                Subject: Diabetes and Endocrinology
                Subject: Physiology/Cardiovascular Physiology and Circulation
                Subject: Diabetes and Endocrinology/Type 2 Diabetes

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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