“To function at its best, your brain needs neuron- and synapse-supporting factors, including certain hormones, trophic factors, and nutrients.” 

Brain-derived neurotrophic factor (BDNF) plays an important role among these synapse-strengthening and neuron-boosting compounds says Dr. Dale Bredesen, well known for his role in Alzheimer’s research.  Obviously BDNF plays an important role in the brain, but what exactly is it and what does it do?

What is BDNF?

Brain-derived neurotrophic factor (BDNF) is a critical brain-growth protein produced inside neurons (nerve cells) and is one of the most active of the neurotrophic family of growth factors.  Neurotrophic factors are molecules that enhance the growth of neurons and are also involved in neuronal survival, synaptic plasticity, and the formation of long-lasting memories.

BDNF is a protein that is associated with cognitive improvement, as it regulates axonal growth, neuronal survival, and differentiation of neurons.  BDNF also affects synaptic plasticity, which refers to the synapse’s ability to change and adapt from experience, and is linked to adult neurogenesis, referring to the growth of new brain cells.

Like most proteins in the body, BDNF is encoded by a gene.  The BDNF gene provides the cell’s instructions to make this protein found in the brain and spinal cord.  Interestingly, the gut microbiota can modulate BDNF function in the central nervous system, for example by changes in the availability and actions of short chain fatty acids in the brain.

The role of BDNF:

  • BDNF plays a key role in the forming of new neurons during neurogenesis, which primarily happens in the hippocampus, the center of memory and learning in the brain.  Neurogenesis refers to the development and growth of new nerve cells in the brain.
  • BDNF enhances the differentiation of newly formed neurons into functional neurons.  Neuronal differentiation refers to the final stage in the development of neurons, when they increase in size, form more dendrites, extend their axons further, and form new connections with other neurons.
  • BDNF is known to protect existing neurons, ensuring their survival, and encouraging the connections (synapses) between them.
  • BDNF significantly increases the strength of electrical impulses that pass between neurons, which leads to improved connectivity and functionality.
  • BNNF has been found to be related to many biological functions, including receptor activity and synapse stability.
  • BNNF promotes axonal growth of motor and sensory neurons.
  • BDNF enhances synaptic transmission by both pre- and postsynaptic mechanisms.
  • BDNF encourages synapse formation, which is the connection of one neuron to the next one, which is vital for learning, thinking, and higher levels of brain function.  As such, BDNF enhances learning and memory.
  • Mouse studies have shown that gut bacteria can modulate the production of important brain chemicals such as BDNF and interestingly, gut microbiota induced hippocampal BDNF expression might be mediated by the vagus nerve.  BDNF is vitally dependent on the balance of bacteria that live in the gut, says Dr. David Perlmutter in his book Brain Maker.
  • BDNF has a widespread distribution in the central nervous system.
  • BDNF is required for the normal development of several areas of the nervous system.

Exercise affects the production of BDNF:

Studies have shown how physical activity plays a major role in protecting and preserving brain function.  Dr. Perlmutter says it boils down to five benefits:

  • Controlling inflammation.
  • Increasing insulin sensitivity.
  • Influencing better blood sugar control.
  • Boosting levels of BDNF
  • Expanding the size of the memory center

He also says exercise makes neurons nimbler and able to multitask, while increased levels of BDNF play a role by strengthening cells and neurons, bolstering the connections between neurons, and sparking neurogenesis.

  • Physical activity upregulates BDNF and neurogenesis in the hippocampus, while stress downregulates BDNF.
  • Neurotrophic factors are released into the bloodstream and increasingly so during exercise.
  • Certain types of exercise, for example regular aerobic exercise such as walking, running, cycling and swimming, have been shown to substantially (threefold) increase BDNF synthesis in the human brain.
  • BDNF also plays a role in metabolism, as the expression of BDNF increases in skeletal muscle in response to contraction and physical exercise.  The exercise induced increases in BDNF in the blood stream are positively correlated with an increment in muscle strength.
  • Many nutritional and environmental factors can increase BDNF levels, but exercise has the largest effect.
  • Longer durations of exercise progressively increase BDNF levels in the hippocampus and remain elevated for weeks.
  • High-intensity aerobic interval exercise, alternating short periods of intense anaerobic exercise with less intense recovery periods, seems to be more effective at increasing BDNF levels.
  • Weight training also increases BDNF levels, but not to the same extent as high-intensity aerobic interval training.
  • The harder you train, the bigger the gain in BDNF levels.

Effects of reduced levels of BDNF:

The dysregulation of BDNF signaling and decreased levels of BDNF are associated with several neurodegenerative disorders, such as depression, schizophrenia, Alzheimer’s, epilepsy, anorexia nervosa, and obsessive-compulsive disorder. 

Studies have revealed how blood levels of BDNF relate to risk for developing dementia and Alzheimer’s.  When levels of synapse- and neuron boosting compounds such as BDNF runs low, the brain responds by producing amyloid, which is one of the many contributors to cognitive decline and Alzheimer’s.  The fatty membrane that surrounds brain cells contain a protein molecule called beta-amyloid, which can cause plaque build-up outside the cells of the brain when it clumps together and gung up the spaces (the synapses) between neurons.  As neurons communicate with each other via the synapses, the damage caused by the plaque to the synapses can result in synapses that stops functioning, which have devastating consequences for the transfer of signals (communication) between neurons.  This can ultimately kill neurons.

Obesity as well as elevated blood sugar levels and Type 2 diabetes are associated with reduced levels of BDNF.

Higher levels of BDNF are associated with a decrease in appetite.

There is emerging evidence in small studies of lower BDNF levels in patients with chronic heart failure and stroke.

Sleep disturbances and sleep loss results in a higher vulnerability to stress, which is associated with decreased levels of BDNF.

What is BDNF and why is it so important to your health? - Medical Detective  MD

BDNF and lifestyle:

The gene that turns on the production of BDNS, located on chromosome 11 region p13-14, is activated by lifestyle factors under our control, such as physical exercise, caloric restriction (the production of BDNF shoots up with a low-calorie diet), following a ketogenic diet (low in carbs, with healthy fats), getting a good night’s sleep, and adding nutrients such as the healthy Omega 3 fat DHA (docosahexaenoic acid) to the diet. 

DHA plays a role in regulating gene expression to produce BDNF.  DHA is an important building block for the membranes that surround brain cells and is of particular importance for synapses, which are crucial for efficient brain function.  Interestingly, about two-thirds of the brain’s dry weight is fat, of which one quarter is DHA.  DHA also plays an important role in the regulation of inflammation.

Conclusion:

BDNF plays an important role in cognitive improvement and brain health.  Reduced levels of this brain growth factor have dire consequences on cognitive health and brain functioning.  Fortunately, studies have shown that we can boost production of this important molecule through strenuous aerobic exercise and a healthy lifestyle, to not only assist with important biochemical processes in the brain, but also to slow down age related cognitive decline and help prevent some of the serious neurodegenerative diseases.

References:

Brain Maker.   Author: Dr David Perlmutter.  Book published 2015 by Little, Brown and Company, USA.  P 323.

Grain Brain.  Author: Dr David Perlmutter.  Book published 2014 by Yellow Kite Books, UK.  P 323.

The Stress Code.  From surviving to thriving.  Author: Richard Sutton.  Book published 2018, Pan Macmillan, South Africa.  P 318.

The End of Alzheimer’s.  The first programme to prevent and reverse the cognitive decline of dementia.  Author: Dr Dale Bredesen.  Book published 2017 by Penguin Random House, UK.  P. 308

BDNF Gene.  Published online.  MedlinePlus.  US National Library of Medicine.  (www.medlineplus.gov)

How stem cells form neurons.  Published online.  The brain from top to bottom.  Institute of Neurosciences, Mental Health and Addiction.  McGill University.  Canada.  (www.thebrain.mcgill.ca)

Association between reduced brain-derived neurotrophic factor and serious cardiovascular conditions.  Published July 2019.  Indian Journal of Medical Research.  National Center for Biotechnology Information.  National Library of Medicine.  National Institutes of Health.  USA.  (www.nbci.nlm.nih.gov)

An integrative review of brain-derived neurotrophic factor and serious cardiovascular conditions.  Published October 2020.  PubMed.  National Center for Biotechnology Information.  National Library of Medicine.  National Institutes of Health.  USA.  (www.nbci.nlm.nih.gov)

Roles of gut microbiota in the regulation of hippocampal plasticity, inflammation, and hippocampus-dependent behaviors.  Published 27 January 2021. Frontiers in Cellular and Infection Microbiology.  (www.frontiersin.org.)

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