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Examining the Roles of BDNF

Brain-derived neurotrophic factor (BDNF) is a unique protein in the brain that stimulates the development, differentiation, and protection of neuronal survival in the central and peripheral nervous systems. This protein (and its mRNA) is found in nearly all brain regions and it is strongly linked to cognitive and mental health as it influences mood, memory, and sleep.

BDNF and Brain Health

BDNF is a member of the neurotrophin family of growth factors including nerve growth factor. Its levels are low during fetal development, but they markedly increase after birth, and then decrease in aging adults as the total number of brain cells declines. Low levels have also been associated with various neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and multiple sclerosis (MS). Oxidative stress, excitotoxicity, and neuroinflammation, synaptic dysfunction, and neuronal death are characteristics of these conditions, which are often linked with neurotoxicity induced by stress, radiation, chemicals, or metabolism diseases.

BDNF signaling pathways lead to activation of neural plasticity, neurogenesis, stress resistance and neuronal cell survival. Therefore, enhancing BDNF may be a tool for stimulating neuron regeneration and managing various neurodegenerative and mood conditions.

In in vivo studies, exogenous BDNF “increased dendritic length and complexity of pyramidal neurons in the developing visual cortex in a layer-specific manner, suggesting that BDNF not only enhanced neuronal growth but also modulated a specific pattern in dendritic growth.” Using a trauma model, a continuous application of BDNF enhanced neuronal survival and neurogenesis in the hypothalamus and, interestingly, dietary restriction enhanced the clinical outcome, indicating that energy balance also plays a role.

The roles of BDNF in synaptic plasticity was shown when its application to sections of the hippocampus resulted in increased NMDA levels and calcium influx, while relieving magnesium blocks of NMDA receptors in neurons. This effect increases pre-synaptic vesicle cycling, which enhances long-term potentiation and synaptic plasticity.

BDNF also modulates neuronal health and function through its close interaction with GABAergic systems. It is “one of the crucial mediators of long-term potentiation at glutamatergic and GABAergic synapses in the CNS” and its influence is both direct and indirect. Reduction of BDNF (which is common in neurodegenerative diseases) can result in an imbalance in excitatory/inhibitory neurotransmission, including dysregulation of GABAergic transmission, leading to neurodegeneration.

Additional Benefits of BDNF

Additional non-neuronal related functions of BDNF include promoting angiogenesis and survival of endothelial cells, vascular smooth muscle cells, and cardiomyocytes, immunomodulation, improved glucose metabolism, increased β-oxidation, regulation of gene expression, hormone regulation, appetite suppression, and weight management. Clearly, BDNF plays many important roles and is vital to overall health and wellness.

Improving BDNF Levels

It was previously thought that there were no nutritional interventions capable of stimulating BDNF production in concentrations adequate to support brain cell regeneration. Evidence now exists for the use of omega-3 polyunsaturated fatty acids (PUFAs) and coffee fruit concentrate as effective in boosting BDNF.

Coffee fruit concentrate is an extract from the whole coffee cherry, including the flesh of the berry that surrounds the coffee bean, and contains several distinctive compounds not found in coffee beans themselves. In clinical studies, a single dose of coffee fruit concentrate increased plasma concentrations of BDNF by 143 percent.

Studies have suggested that the interaction between omega-3 (PUFAs) and BDNF is a primary mechanism for its cytoprotective properties. Omega-3 PUFAs not only protect cell membranes and fight against cellular oxidative stress but directly normalize BDNF levels. PUFAs and their metabolites have also been known to bind to BDNF and exert an allosteric effect. Some studies have shown a direct increase in the expression of BDNF with omega-3 PUFA supplementation and especially with docosahexaenoic acid (DHA) which targets cell membranes.

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