Alternative Therapies for Neuroplasticity
Aging is an inevitable phenomenon that is often associated with cognitive decline and dementia and other pathologies. The number of elderly across the globe is estimated to reach 2.1 billion by the year 2050 (Phillips, 2017). Because conventional drug-based therapies are not demonstrating to be very effective, alternative therapies are increasingly being investigated. The good news is, there is some evidence that lifestyle modifications, such as exercise, cognitive engagement, and diet, are effective strategies for maintaining brain health during aging. This is due to the concept that the brain has the ability to respond to different stimuli (Murphy, Dias, & Thuret, 2014). According to Phillips (2017), physical activity and diet modulate neuroplasticity, and cognitive engagement enhances brain and cognitive reserve. Neuroplasticity is defined as the “ability of neurons in the brain to change and reorganize continuously to meet the dynamic demands of the internal and external environment”(Phillips, 2017). According to Phillips, this process is dependent on membrane depolarization of the neuron, stimulus induced synaptic activity, and changes in the dendritic morphology, all of which are the “central hallmarks” of learning and memory. Below is a summary of some of the lifestyle strategies that can increase neuroplasticity:
- Physical Activity (PA)-Long term physical activity can moderate many of the processes associated with neuroplasticity. For example, long term PA can significantly increase dendritic length and complexity, and spine density in the dentate gyrus of mice (Phillips, 2017). Numerous studies associate higher levels of PA with improved learning and memory, while regular bouts of PA can reduce the risk of cognitive decline in aging adults. Increased levels of PA can increase hippocampal volume supporting the idea that PA may prevent age-related anatomical and physiological functioning, health related quality of life, strength, balance and gait speed (Phillips, 2017). PA has shown clear and consistent promise in promoting neuroplasticity in persons with mood disorders as well, as evidenced with persons with schizophrenia that demonstrate improvement in global cognition, working memory, social cognition, and attention (Phillips, 2017). How does exercise exert some benefits? Scientists believe this can be partly attributed to neurotrophins such as brain derived neurotrophic factor (BDNF) that can play a critical role in the maintenance, growth and synaptic plasticity of neurons involved in emotion and cognition. “The ability of PA to enhance BDNF release and function in the synapse, to promote dendritic spine integrity, and to activate other cellular pathways that contribute to plasticity is a cornerstone for homeostatic processes that maintain, repair, and reorganize circuits damaged during aging and disease” (Phillips, 2017). In fact, BDNF is upregulated (centrally and peripherally) following acute and long -term PA and the changes can last for days. Both resistance and aerobic exercise can affect the increase in BDNF levels once sufficient intensity of PA is achieved. Long term PA can persistently elevate BDNF levels and modulate cognitive function in older adults. Another benefit of long-term PA is that is can upregulate the body’s anti-inflammatory processes, which is important given that chronic inflammation can be linked to cognitive impairment and neurodegenerative disorders. Long term PA can modulate cytokines such as IL-6, IL-8, CRP and TNF which can exert neuroprotective effects. And finally long term PA can mitigate an overactive stress response by attenuating rises in cortisol that are important in the context of hippocampal atrophy (Phillips, 2017). There is evidence that hippocampal neurons exposed to persistently elevated glucocorticoids can retract their dendrites and exhibit fewer dendritic spines and are considered neurotoxic. In essence, a long -term exercise program is a key component in optimizing neuroplasticity.
- Nutritional interventions–Although the brain compromises 2% of the total body weight, it also consumes 20% of the energy derived from nutrients. According to Phillips (2017), dietary factors can modulate synaptic plasticity by altering neurogenesis, inflammation, antioxidant defense mechanisms, neurotrophin levels, and energy metabolism. It should be mentioned that these mechanisms are similar to those induced by PA. Bioactive substances in food represent a target for lifestyle interventions that may promote a health aging brain and preserve cognitive function, especially for older adults who are at risk of nutritional deficiencies. This is where the role of a nutritionist really blossoms! Below are a few of the recommended nutritional interventions:
a. Curcumin- Curcumin is an aromatic polyphenol that has a distinct aroma and widely used in India as a spice (Park, Amin, Chen, & Shin, 2013). Polyphenols are the most abundant antioxidant in the diet (Scalbert, 2005). Polyphenols are found in fruits, vegetables, tea, wine, juices, plants and herbs, are thought to be able to mitigate neurodegenerative disease and oxidative stress via processes of metabolic homeostasis and promotion of synaptic plasticity (Phillips, 2017). Curcumin, the most ubiquitous curcuminoid and active ingredient in the spice turmeric, has been consumed for medicinal purposes for thousands of years (Murphy et al., 2014). Curcumin is classified as an anti-proliferative, antioxidant and carcinogen blocking agent (Park et al., 2013). “The antioxidant capabilities of curcumin appear to stem from its unique structure that can donate H-atoms or transfer electrons from two phenolic sites, allowing it to scavenge free radicals easily” (Phillips, 2017). 1000mg a day of turmeric extract have been suggested to demonstrate significant anti-inflammatory effects as evidenced by circulating IL-6 concentrations. Curcumin supplementation also effected circulating TNF-a, which is important because chronic inflammation can dysregulate neurotransmission and trophic signaling and disrupt processes such as neurogenesis and neuroplasticity. In addition, chronic inflammation can contribute to glutamate mediated excitotoxicity and loss of dysfunction of glial cells (Phillips, 2017).
b. Green tea catechins- Green tea is one of the most popular beverages consumed around the world for its antioxidant potential (Du et al., 2012). Of all the antioxidant compounds, the major constituents are the polyphenols, including phenolic acids and catechins (Du et al., 2012). Green tea’s EGCG is thought to exert their anti-oxidant power by preventing specific DNA damage by reactive oxygen species (ROS) (Kotecha, Takami, & Espinoza, 2016). “EGCG has been shown to have neuroprotective functions that include antioxidant, iron chelating, and anti-inflammatory properties” (Phillips, 2017). EGCG can facilitate glutamate release by enhancing calcium ion entry in voltage dependent calcium channels, which is important in the context of learning and memory. EGCG can also increase synaptic plasticity to evoke long term potentiation as well as enhance cell proliferation to increase the number of progenitor cells in the hippocampus.
c. Omega-3 fatty acid-PUFA-Omega-3 enriched diets and those with high levels of fish and nut oils have been associated with positive brain health. The omega-3 fatty acids DHA and EPA are fundamentals to CNS function, due partly to the lipid nature of the brain. Foods such as fish, meat, eggs and some plant foods are the major sources of the EPA and DHA consumed. DHA is a key component of neural cell membranes and essential to appropriate neural functioning. Interestingly, the omega-3 fatty acids can modulate cholesterol induced reductions in membrane fluidity by displacing cholesterol from the plasma membrane, which can thus increase membrane fluidity, increase the number of receptors, enhance receptor affinity, improve ion channel functionality, and modulate gene expression of proteins involved in signal transduction pathways (Murphy et al., 2014). Other roles DHA has include stabilizing molecular mechanisms involved in mitochondrial function, brain glucose utilization, oxidative stress, and can contribute to epigenetic changes that confer “resilience to metabolic perturbations” (Phillips, 2017). “Together, these effects lead to improved neurotransmission and signaling, and therefore, to optimal cognitive functioning” (Murphy et al., 2014).
d. Calorie restriction/ Intermittent Fasting-Calorie restriction (CR) has become increasing popular in recent times due to its association to increased lifespan and improved health (in the context of adequate nutrients). CR was evidenced to benefit “healthspan”, which is defined as the years lived free of pathology and disease. “Convergent evidence suggests that a reduction of caloric intake by 20–40% extends the lifespan of organisms throughout phylogeny” (Phillips, 2017). For example, a 30% reduction in calories for 3 months has been associated with a 20% improvement in verbal memory in healthy elderly adults (Phillips, 2017). Calorie restriction is associated with an increase in cellular repair of DNA, reduction of oxidative stress, improved glucose metabolism, and optimized immune and endocrine function (Phillips, 2017). Calorie restriction, according to Phillips (2017), can counteract age-related alteration in the expression of genes related to synaptic transmission. “For example, caloric restriction increases the expression of BDNF, TrkB, and NR2B subunits of NMDA receptors to mitigate age-related decrements in the hippocampus” (Phillips, 2017). It was interesting to read that CR is regarded as an example of “hormesis”, in which a small exposure is induces a mild and beneficial stress, but too much can be detrimental. CR appears to improve the resilience of synapses to metabolic and oxidative damage while being able to modulate the total number, structure, and functional status of synapses, according to Murphy et al (2014). CR can also stabilize the levels of glutamate receptors and synaptic proteins required for excitatory transmission, which is thought to lie beneath hippocampal-dependent learning and memory. Intermittent fasting (IF) also can exert neuroprotective effects as well. IF can increase synaptic resilience and function, stress protein chaperone levels and neurotrophic factors.
- Use it or lose it– Higher levels of brain activity, such as in higher education or cognitively demanding jobs, are associated with a reduced risk of cognitive impairment. According to Phillips (2017), higher education can protect against cognitive deficits in elderly individuals with white matter lesions. Additionally, leisure activity and social activities also have “precognitive effects” as well. These include activities such as reading, discussion groups, technology use, participation in card games, solving puzzles, traveling, theater, or participating in social events and gatherings. These improvements are associated with a concept called “reserve”. “Brain reserve refers to structural differences that increase tolerance to pathology, whereas cognitive reserve refers to variability in approach to task performance” (Phillips, 2017). People who engage in intellectually stimulating activities demonstrate less hippocampal trophy with aging. According to Phillips (2017):
Enriched environments infused with challenging activities are thought to effectuate the formation of new dendritic branches and synapses. These morphological changes then deepen the brain’s capacity to resist insult while increasing augmentation of glial support cells, enhancement of the brain’s capillary network, and the induction and incorporation of new neurons.
I should also mention that nutrition and physical activity are complementary and work synergistically in enhancing neuroplasticity. The effects of exercise on oxygen consumption combined with the mitochondrial activity of food consumption can together modulate signaling pathways lined to neuronal function and brain plasticity. “Indeed, it is possible that exercise
potentiates the health-promoting effects of diet components and vice versa at the cellular and molecular levels” (Murphy et al., 2014). This is evidenced in an example that exercise can enhance mechanisms that preserve DHA on the plasma membrane which can in turn enhance neurotransmission, both of which can engage NDFN-mediated synaptic plasticity (Murphy et al., 2014). “Similarly, exercise and flavonoid-enriched diets together promote the elevation of genes that promote brain plasticity whilst decreasing expression of markers known to compromise this plasticity, including those related to inflammation and cell death” (Murphy et al., 2014). The same model can be applied to the synergistic effects of CR and exercise. In the context of CR, 12.5% of the energy restriction comes from the restricted calorie diet, and the other 12.5% comes from increased energy expenditure from exercise.
Du, G. J., Zhang, Z., Wen, X. D., Yu, C., Calway, T., Yuan, C. S., & Wang, C. Z. (2012). Epigallocatechin Gallate (EGCG) is the most effective cancer chemopreventive polyphenol in green tea. Nutrients, 4(11), 1679-1691. doi:10.3390/nu4111679
Kotecha, R., Takami, A., & Espinoza, J. L. (2016). Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence. Oncotarget, 7(32), 52517-52529. doi:10.18632/oncotarget.9593
Murphy, T., Dias, G. P., & Thuret, S. (2014). Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plast, 2014, 563160. doi:10.1155/2014/563160
Park, W., Amin, A. R., Chen, Z. G., & Shin, D. M. (2013). New perspectives of curcumin in cancer prevention. Cancer Prev Res (Phila), 6(5), 387-400. doi:10.1158/1940-6207.capr-12-0410
Phillips, C. (2017). Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging. Neural Plast, 2017, 3589271. doi:10.1155/2017/3589271
Scalbert, A. J., Ian T; Saltmarsh, Mike. (2005). Polyphenols and Beyond. American Journal of Clinical Nutrition, 81, 215-217.