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Brain-Derived Neurotrophic Factor – Growth Factor Demonstrates Promise in the Protection Against Alzheimer’s Disease

Posted Oct 17 2009 9:36pm
By Ralph Sanchez, L.Ac.CNS,D.Hom.

One of the longest held thoughts about damage to our brain’s cells (neurons) was that once they were lost, it was a fait accompli. Damaged neurons were considered damaged goods, never to regain their function, and without any hope for regeneration. Fortunately, for those concerned about recovery from brain trauma, stroke, and the neurological damage associated with Alzheimer’s disease (AD), there is promising research indicating that growth factors in the brain, not only promote brain structure and function associated with memory and learning, they can promote brain growth and recovery from damaging events to the brain.

Brain Derived Neurotrophic Factor

Growth factors comprise a varied family of proteins and hormones that regulate and control cellular growth and differentiation (cell division). In the brain, nerve growth factors (neurotrophins) have recently been discovered to play a vital role in neuronal growth, development and survival. In the brain, neurotrophins are vital signaling molecules * that regulate the function and structure of connective junctures (the synapse) between brain cells (neurons), and the processes that lead to learning and memory formation.

Promising research is emerging around one particular neurotrophin-Brain-derived neurotrophic factor ** (BDNF), in Alzheimer’s disease and other neurological disorders. BDNF, one of 4 identified neurotrophins ***, was originally first identified in the brain.  It was later found in the peripheral nervous system and other tissues. In the brain, BDNF is normally produced in the entorhinal cortex, the hippocampus, and other vital areas of the brain (cerebrocortex) where memory and learning are facilitated.

How important is BDNF? In studies, the inhibition of BDNF and Neural Growth Factor (NGF) to neurons stimulates the molecular events typical of the AD process. Amyloid beta (AB), the protein that accumulates and aggregates into the plaque lesions of AD, is increased in a neuronal environment of BDNF and NGF deprivation. The interruption of BDNF and NGF signaling sets forward the toxic mechanisms that induce the death and loss of neurons. (1) On the other hand, evidence is mounting indicating that augmentation of neurotrophic factors, BDNF and Nerve Growth Factor (NGF), prevent or reduce the loss of neurons in Alzheimer’s disease models. (1)

One of the most promising interventions for rescuing cognitive function in AD is neural stem cell therapy. Stem cell treatment portends to be the proverbial cure for the loss of memory and cognitive function related to neurological disease. Neural stem cell transplantation can restore cognitive function in neurological diseases like AD. In animal research, stem cell therapy restored cognitive function in mice that exhibited the typical lesions associated with AD. In spite of the extensive plaques and tangles present, stem cell transplantation restored memory and spatial learning **** to aging mice via BDNF mediated increases on hippocampal synaptic density.***** (2)

The Synapse

In the brain, BDNF promotes the optimum communication between neurons by enhancing “plasticity” at the synapse (see illustration below). In my article on the role of insulin in brain and synaptic plasticity, I described brain plasticity, as “the brain’s malleability-its capacity for adaptive change”. This adaptive capacity by the brain is reflected in the ability to integrate information and experiences, and through higher cognitive processing, anchor them into learning and memory formation.

The synapse is a critical locus in this adaptive capacity. The integration of learning and subsequent memory formation, and the plasticity that enhances that process, is reflected and promoted by the formation of new synapses that extend the network of communication, and the strength** of the synaptic connection. BDNF plays an important role in the survival of neurons, their growth (axons and dendrites), and the formation and function of the synapse. (2) Without sufficient BDNF and other neurotrophic factors, neurons die. (3)

synapse

The synapse is a crucial messaging exchange center between neurons. Synaptic junctions between neurons are where the cell-to-cell brain circuitry is facilitated. This complex neural circuitry and its growth and development, is what facilitates learning and memory formation. BDNF is key in both the growth and formation of the network of synapses, and the signaling mechanisms that underlies synaptic function and plasticity. (2) Since the role of BDNF is essential in the structural and functional elements integral to learning and memory formation, it has become a research target in its potential role in mitigating the degenerative process associated with AD and other neurological disorders.

BDNF & Alzheimer’s disease

To summarize some points made above, BDNF levels are the highest in the areas of the brain associated with memory and learning. The deprivation of neurotrophic factors, BDNF and NGF, leads to the development of AD. Lack of BDNF signaling at the synapse, is a link in the cascade of amyloid beta formation that leads to the toxic aggregation and plaque lesions associated with AD. (Please read my article on Amyloid Plaque & Tangles).

Until recently, the research to date on the role of BDNF in AD risk has centered on laboratory cultures of hippocampal and other brain tissues. Now, a recent animal study (2/2009) at the University of California, San Diego (UCSD), affirms the promising role of BDNF in the prevention, and the possible reversal of neuronal degeneration, and cell death, associated with AD. (4) Memory loss, cognitive impairment, brain cell degeneration, and cell death were prevented or reversed in several animal models after treatment with BDNF. The UCSD study treated animals had widespread lesions associated with AD (plaques & tangles). Despite the cognitive impairment present, BDNF treatment improved the performance of impaired animals in a variety of learning and memory tests, as compared to control groups not treated with BDNF.

The UCSD study on the role of BDNF in AD is particularly significant as it showed that BDNF treatment might potentially provide long-lasting protection by slowing, or even stopping, the progression of Alzheimer’s disease. Mark Tuszynski, M.D., Ph.D., professor of neurosciences at the U.C. San Diego School of Medicine, reported: “When we administered BDNF to memory circuits in the brain, we directly stimulated their activity and prevented cell death from the underlying disease.”

Optimizing BDNF

Optimizing BDNF in the brain can provide two essential benefits for brain health:

•    Enhance cognitive function, and

•    Protect your brain from the degenerative processes associated with aging, as well as the neurological decline that marks AD.

The good news is that there are core nutrition and lifestyle factors that directly influence BDNF levels and benefits to the brain.  Numerous studies demonstrate the benefit of exercise on cognitive function in healthy individuals, as well as those afflicted with AD (see video below). Nutrition and stress also mediate a significant impact on the risk for AD. In related research, it is shown that these same factors influence BDNF levels and function.

In my next article on BDNF, I will delineate more on these nutrition and lifestyle factors, and their influence on optimizing BDNF, and how key nutraceuticals can also enhance BDNF in the brain.

For those of you reading this article at another website other than TheAlzheimersSolution.com, please visit the Neurotrophic Factors category at TheAlzheimersSolution.com.


* Signaling molecules
…chemical messengers that serve to transmit information between cells.

** Neurotrophic factors
–derived from the Greek “neuro” for nerve and “troph” for nourish.

*** The family of neurotrophins
includes BDNF, Neural Growth Factor (NGF), Neurotrophin-3 (NT-3) and Neurotrophin-4 (NT-4)

**** Spatial learning…implies the ability to orient oneself in relation to their environment

***** Synaptic density: the number of connections via synaptic junctions between neurons

****** Synaptic strength…the established ease of communication across the synapse (between neurons).
The repetitive and frequent stimulation of the neuron in a learning process establishes synaptic strength-i.e. learning how to write, or play an instrument, strengthens the neural pathway, and establishes the synaptic strength between neurons.

References

1. NGF and BDNF signaling control amyloidogenic route and Aβ production in hippocampal neurons

Carmela Matrone, Maria Teresa Ciotti, Delio Mercanti, Roberta Marolda*, and Pietro Calissano

PNAS  September 2, 2008   vol. 105  no. 35  13139-13144

2. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease

Mathew Blurton-Jonesa,Masashi Kitazawaa,Hilda Martinez-Coriaa, Nicholas A. Castelloa, Franz-Josef Müllerb, Jeanne F. Loring, Tritia R. Yamasakia, Wayne W. Poona, Kim N. Greena and Frank M. LaFerla

PNAS  August 11, 2009   vol. 106  no. 32  13594-13599
http://www.pnas.org/content/106/32/13594.abstract

3. Role for brain-derived neurotrophic factor in learning and memory.

Yamada K, Mizuno M, Nabeshima T.

4. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease.

Nagahara AH, Merrill DA, Tuszynski MH, et al.

Nat Med 2009; E-pub 2009 Feb 8.

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