Potential therapeutic uses of BDNF in neurological and psychiatric disorders.
ABSTRACT The growth factor brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase receptor type B (TRKB) are actively produced and trafficked in multiple regions in the adult brain, where they influence neuronal activity, function and survival throughout life. The diverse presence and activity of BDNF suggests a potential role for this molecule in the pathogenesis and treatment of both neurological and psychiatric disorders. This article reviews the current understanding and future directions in BDNF-related research in the central nervous system, with an emphasis on the possible therapeutic application of BDNF in modifying fundamental processes underlying neural disease.
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ABSTRACT: OBJECTIVES: Physical exercise up-regulates brain-derived neurotrophic factor (BDNF) in brain and blood. However, there is yet no consensus about the adequate blood processing conditions to standardize its assessment. We aimed to find a reliable blood sample processing method to determine changes in BDNF due to exercise. DESIGN AND METHODS: Twelve healthy university students performed an incremental cycling test to exhaustion. At baseline, immediately after exercise, and 30 and 60minutes of recovery, venous blood was drawn and processed under different conditions, i.e. whole blood, serum coagulated for 10minutes and 24hours, total plasma, and platelet-free plasma. BDNF concentration was measured by ELISA. RESULTS: Exercise increased BDNF in whole blood and in serum coagulated for 24hours when corrected by hemoconcentration. We did not find effects of exercise on BDNF in serum coagulated for 10minutes or in plasma samples. Plasma shows heterogeneous BDNF values in response to exercise that are not prevented when platelets are eliminated whilst homogeneous BDNF levels were found in whole blood or serum coagulated for 24hours samples. CONCLUSIONS: In exercise studies, BDNF levels should be adjusted by hemoconcentration. Our data highlight the importance of blood sample selection since the differences between each one affect significantly the BDNF factor changes due to exercise.Clinical Biochemistry 11/2014; 1(3). DOI:10.1016/j.clinbiochem.2014.11.013 · 2.23 Impact Factor
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ABSTRACT: Alpha-linolenic acid (ALA) is plant-based essential omega-3 polyunsaturated fatty acids that must be obtained through the diet. This could explain in part why the severe deficiency in omega-3 intake pointed by numerous epidemiologic studies may increase the brain’s vulnerability representing an important risk factor in the development and/or deterioration of certain cardio- and neuropathologies. The roles of ALA in neurological disorders remain unclear, especially in stroke that is a leading cause of death. We and others have identified ALA as a potential nutraceutical to protect the brain from stroke, characterized by its pleiotropic effects in neuroprotection, vasodilation of brain arteries, and neuroplasticity.This review highlights how chronic administration of ALA protects against rodent models of hypoxic-ischemic injury and exerts an anti-depressant-like activity, effects that likely involve multiple mechanisms in brain, and may be applied in stroke prevention. One major effect may be through an increase in mature brain-derived neurotrophic factor (BDNF), a widely expressed protein in brain that plays critical roles in neuronal maintenance, and learning and memory. Understanding the precise roles of ALA in neurological disorders will provide the underpinnings for the development of new therapies for patients and families who could be devastated by these disorders.BioMed Research International 10/2014; · 2.71 Impact Factor
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ABSTRACT: Brain-derived neurotrophic factor (BDNF) regulates multiple biological processes ranging from central nervous system development and function to neuroinflammation and myogenic differentiation and repair. While coordination of BDNF levels is central in determining the biological outcome, mechanisms involved in controlling BDNF levels are not fully understood. Here we find that both short (BDNF-S) and long (BDNF-L) BDNF 3'UTR isoforms contain conserved adenylate- and uridylate rich elements (AREs) that may serve as binding sites for RNA-binding proteins (ARE-BPs). We demonstrate that ARE-BPs tristetraprolin (TTP) and its family members butyrate response factor 1 (BRF1) and 2 (BRF2) negatively regulate expression from both BDNF-S and BDNF-L containing transcripts in several cell-lines and that interaction between TTP and AU-rich region in proximal 5' end of BDNF 3'UTR is direct. In line with the above, endogenous BDNF mRNA co-immunoprecipitates with endogenous TTP in differentiated mouse myoblast C2C12 cells and TTP overexpression destabilizes BDNF-S containing transcript. Finally, RNAi-mediated knock-down of TTP increases the levels of endogenous BDNF protein in C2C12 cells. Our findings uncover TTP as a novel regulator of BDNF assisting future studies in different physiological and pathological contexts.SpringerPlus 09/2014; SpringerPlus 2014(3):502. DOI:10.1186/2193-1801-3-502