Brain derived neurotrophic factor (BDNF) is the most prevalent neurotrophin in the brain.¹⁹

Its depletion in certain neuropsychiatric, neurodegenerative and neurodevelopmental disorders have made it a novel target for researchers, with its implications being widespread.¹

The ability of CNS neurons to adapt to changes in their environment, for example in disease or injury is known as neural plasticity and BDNF plays a key function in this.

In addition, BDNF is involved in the development and survival of neurotransmitter neurons, as well as neurotransmitter release including; serotonergic, dopaminergic, GABAergic and cholinergic.¹

Neurotrophins are a family of polypeptide growth factors that are responsible for regulation of neuronal and nonneuronal cells, including proliferation, survival, differentiation and death.²  In the developing infant, brain neurotrophins are responsible for regulating brain development. As the body ages, they are responsible for central nervous system plasticity.² 

Clinical presentations in which BDNF is implicated includes:

Depression

In major depressive disorder (MDD), treatment focus has centred around neurotransmitter depletion, with drug classes developed to counteract this.³ However recent research is pointing to involvement of BDNF, known as the “neurotrophic hypothesis”.³ Furthermore, BDNF has been demonstrated to increase after four weeks of administration of several classes of antidepressant medication,⁴ which may account for the time required for antidepressants to exert their therapeutic benefit.³

Stress, a contributor to MDD⁵ has been demonstrated to reduce BDNF. Interestingly, the structural changes of the hippocampus and prefrontal cortex observed in MDD may now be attributed to this reduction, as well as reductions in a BDNF receptor; tropomyosin-related kinase B (TrkB) further impacting the effect of BDNF.¹

Features of depression, including anhedonia, helplessness and cognitive impairment are likely attributed to these structural hippocampus and prefrontal cortex changes², while impairment of neural plasticity can be a contributor to suicidal behaviour.⁴ Conversely, animal models have demonstrated antidepressant effects after intracerebroventricular administration of BDNF.⁶

Cognition and Neurodegenerative Disorders

The implications of BDNF on cognitive function, including learning and memory have also been widely studied. Its modulation of synaptic plasticity, transmission and architecture is key to this function.³ Long term memory is attributed to a form of synaptic plasticity called long term potentiation (LTP) in the hippocampus, of which BDNF is critical.⁷

Cognitive Performance and Memory

A cross-sectional observational study of over 4000 individuals assessing serum BDNF and cognitive function in the elderly found that low serum BDNF was associated with poorer scores in cognitive function tests, specifically story memory and digit symbol substitution.⁹

While rat studies have also demonstrated the role of BDNF in memory. One such study found that intrahippocampal administration of BDNF improved spatial memory task performance in a water maze, compared to controls.⁸

Alzheimer’s Disease

BDNF is now thought to be involved in the pathology of Alzheimer’s disease (AD). A study exploring proBDNF (BDNF precursor) and mature BDNF found significant reductions in proBDNF and mature BDNF in those with mild cognitive impairment and AD comparison to controls. ProBDNF was found to be 30% lower in AD patients and 40% lower in end stage AD. Mature BDNF was reduced by 62% in AD10. Additionally, this study found that the decrease in mature BDNF and proBDNF occurred before the decline in choline acetyltransferase activity – known to occur in later stage AD.

Herbal Considerations

Naturopathically, we have many herbs in our arsenal that have been demonstrated to increase BDNF, many of which herbalists through the ages have been using for their antidepressant and cognition enhancing activity. While much of this research is preclinical, clinical studies are starting to emerge which confirm the in vitro and in vivo studies available.

St. John’s Wort

A clinical study exploring the effect of pharmaceutical antidepressants and St. John’s wort on BDNF levels in depressed patients found that St. John’s wort and selective serotonin reuptake inhibitors both upregulated BDNF. BDNF was shown to normalise in remission of depression.¹¹  While an animal study giving chronically stressed mice 350mg/kg of St. John’s wort demonstrated a normalisation of reduced BDNF levels after administration of St. John’s wort.¹²

Bacopa

In vitro studies have demonstrated that bacopa prevented reduction of BDNF with administration of scopolamine and sodium nitroprusside,¹³ while numerous animal studies have shown efficacy. A rat study exploring chronic unpredictable stress (CUS) induced depression, found that rats exposed to CUS had lower BDNF levels in comparison to controls, however daily administration of bacopa to rats exposed to CUS not only reduced depressive behaviour, but also improved BDNF levels in the hippocampus and frontal cortex.¹⁴

Another rat study exploring the cognition enhancing effects of bacopa evaluated its activity against scopolamine-induced amnesia. Bacopa improved the scopolamine induced impairment through normalisation of neurotransmitters and up-regulation of BDNF.¹⁵

Rhodiola

An in vitro study found that salidroside, an active constituent of rhodiola significantly increased BDNF,¹⁶ while an in vivo study found that salidroside increased expression of BDNF and TrkB and attributed its neuroprotective effect to the BDNF/TrkB signalling pathway.¹⁷

Ginkgo

Numerous in vivo studies have found that ginkgo flavonols increase BDNF levels in the hippocampus and prefrontal cortex, with improvements in spatial learning, mood and attention deficit hyperactivity disorder like behaviour.¹³

A clinical study exploring the use of a specific standardised extract of ginkgo in patients with tardive dyskinesia (TD) found, in comparison to controls, patients with TD had lower BDNF levels. After administration of the standardised ginkgo extract at 240mg a day for 12 weeks, serum BDNF levels increased while symptoms of TD improved.¹⁸

Lifestyle Factors

Exercise

Research has also demonstrated an increase of BDNF from exercise, with one study finding increased serum BDNF after both high intensity interval training (HIIT) and continuous high intensity exercise. The result of this study showed a higher BDNF serum concentration in those undertaking HIIT.²⁰

This research brings a new dimension to the clinical management of neuropsychiatric and neurodegenerative disorders from stress through to Alzheimer’s disease and is another example of science confirming the traditional uses of herbs commonly used in practice.

References

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