Neuroscience and Mental Health
Here’s How to Rewire the Brain by Activating BDNF & β-Hydroxybutyrate.
We can initiate neurogenesis and enhance cognitive reserves using simple lifestyle habits.
Introduction to Neurodegenerative Diseases
Neurodegenerative diseases cause suffering for aging people and substantially impact healthcare costs and the economy.
During my cognitive science studies in neuroscience classes, neurogenesis and brain plasticity were among the most exciting topics. I got thrilled when I learned that the brain could grow at any age and we could create cognitive reserves for brain atrophy.
Using this empowering knowledge, my sensible biohacking, transhumanism, and longevity toolbox included powerful tools like BDNF (Brain-Derived Neurotrophic Factor) and BHP (β-hydroxybutyrate).
I learned ways to increase BDNF and BHP naturally, which I want to share in the simplest possible way in this article.
Brain atrophy is natural and inevitable. As we age, we lose specific mental capabilities. BDNF is a crucial factor in human cognition. β-hydroxybutyrate is a remarkable signaling molecule contributing to the increase of BDNF.
Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and depression are examples of brain atrophy. Unfortunately, millions of aging people suffer from these debilitating diseases globally.
One of the measures to mitigate brain atrophy risk is maintaining cognitive reserves. Simple lifestyle changes such as moderate exercise, optimal diet meeting our genetic makeup, stress management, and high-quality sleep can help us create and maintain cognitive reserves.
I introduce what BDNF is, provide a brief review of relevant scientific resources, and present a few practical ways to increase BDNF.
What is BDNF?
BDNF (Brain-Derived Neurotrophic Factor) is a signaling protein for brain plasticity. It is produced by the BDNF genes, which are also in various body parts.
BDNF genes are also part of the neurotrophin group of growth hormones. Neurotrophins are a family of proteins that induce neurons' survival, growth, and functioning.
These hormones contribute to the development of neurons in the brain and are essential for the survival of neurons.
BDNF is active in brain regions such as the hippocampus, the cortex, the basal forebrain, and the cerebrum. These regions help us learn and build new memories. For example, BDNF was observed to be reduced in Alzheimer’s patients.
The hippocampus is critical for our learning process. If this region of the brain is damaged, we experience a learning disability. The necessary knowledge is that the hippocampus needs BNDF for coding information. In short, the lack of BDNF can shorten the synaptic strength in this learning region of the brain.
As confirmed by this scientific paper:
“BDNF is essential to promote the persistence of long-term memory (LTM) storage. The study demonstrates that BDNF induces memory persistence by itself, transforming a non-lasting LTM trace into a persistent one in an ERK-dependent manner. Thus, BDNF is not only necessary but sufficient to induce a late post-acquisition phase in the hippocampus essential for the persistence of LTM storage.”
Even though Hippocampus plays a critical role, there are several other brain regions coordinating learning and skill-building.
So, total brain activity is essential for learning and improving our skills.
Impact of BDNF on Neurodegenerative Diseases
Many scientific studies, as compiled by a comprehensive review in Cellular Neuroscience, depict the association of BDNF in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, multiple sclerosis (MS), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), and depression.
There is evidence of the effect of chronic stress on BDNF and its link to psychiatric disorders.
For example, this study points out:
“The hippocampus is altered by prolonged exposure to aversive situations. A wide variety of strategies have been assessed to reduce the deleterious effects caused by chronic stress. Infusions of BDNF in the rat hippocampus before a chronic restraint stress protocol can protect against the deficits in learning.”
To give you a useful perspective on these diseases, I share five prominent scientific papers touching on each condition from my review of the topic in scientific literature.
1 — BDNF and Depression
As highlighted in this study:
“Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF.”
2 — BDNF and Alzheimer’s Disease
This study published in Nature points out:
“Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer’s disease (AD), which is characterized by the formation of neuritic plaques consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established.”
3 — BDNF and Parkinson’s Disease
This study sees BDNF as a Promising Therapeutic Agent in Parkinson’s Disease.
“Brain-derived neurotrophic factor (BDNF) promotes neuroprotection and neuroregeneration. In animal models of Parkinson’s disease (PD), BDNF enhances the survival of dopaminergic neurons and improves dopaminergic neurotransmission and motor performance. Pharmacological therapies of PD are symptom-targeting, and their effectiveness decreases with the progression of the disease; therefore, new therapeutical approaches are needed.”
4 — BDNF and Huntington’s Disease
This study discusses the role of a brain-derived neurotrophic factor in Huntington’s disease.
“Neurotrophic factors are essential contributors to the survival of peripheral and central nervous system (CNS) neurons, and demonstration of their reduced availability in diseased brains indicates that they play a role in various neurological disorders.”
The paper concentrates on the role of brain-derived neurotrophic factor (BDNF) in the survival and activity of the neurons that die in Huntington’s disease (HD) by reviewing the evidence indicating that it involves profound changes in BDNF levels and that attempts to restore these levels are therapeutically interesting.”
5 — BDNF and Overall Neurodegenerative Diseases
As mentioned in this recent scientific review, altered levels of BDNF, both in the circulation and in the central nervous system (CNS), have been reported to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), multiple sclerosis (MS), and ischemic stroke.
How to Increase BDNF and Maintain Cognitive Reserves
After this brief theoretical unpinning, I want to highlight practical ways to increase BDNF and maintain cognitive reserves.
As mentioned in this study:
“Circulating BDNF levels increase with physical activity and caloric restriction, thus, BDNF may mediate some of the observed associations between lifestyle and the risk for dementia.”
Caloric restriction — in the form of time-restricted eating (intermittent fasting) — and intense exercise contribute to the formation of β-hydroxybutyrate, which is a powerful ketone producing alternative energy to the brain and several other organs. Therefore, one of my reasons to stay in mild ketosis through time-restricted eating is to improve BDNF.
As this study points out, “Beta-hydroxybutyrate Promotes the Expression of BDNF in Hippocampal Neurons under Adequate Glucose Supply. β-Hydroxybutyrate induces BDNF expression by activating cAMP/PKA/p-CREB signaling and enhances H3K27ac level independent on HDAC.”
When we consume liver glycogen and stay in a caloric deficit, the body produces ketones as an alternative energy source, especially for the brain. Ketones are created from lipids. The brain can’t use fat as an energy source directly; however, it happily uses ketones. This is part of our evolution. During the famine, humans survived by this unique energy source. When adequate glucose does not go to the brain, we experience brain fog. Ketones provide alternative energy.
1 — Intense Exercise
Cardio and high-intensity interval training (aerobic exercises) are criticized in some fitness communities associated with muscle loss.
I understand the hesitance in the side effects of excessive cardio, especially for aging adults. However, moderate cardio and HIIT are essential tools to create BDNF.
Resistance training, in the form of weightlifting and calisthenics, is also important. As confirmed by this study, intense resistance exercise increases peripheral brain-derived neurotrophic factors.
As this study articulates:
“It is well established that acute exercise increases circulating levels of BDNF, and numerous studies have sought to characterize this response to improve brain health. Engagement in regular bouts of exercise confers numerous positive effects on brain health across the lifespan. Acute bouts of exercise transiently improve cognitive function, while long-term exercise training stimulates brain plasticity, improves brain function, and helps to stave off neurological disease.”
Exercise reduces insulin resistance and increases β-hydroxybutyrate when incorporated with time-restricted feeding such as intermittent fasting. Ketones, as signaling molecules, can also reduce oxidative stress and inflammation.
2 — Time Restricted Eating (Fasting)
Fasting is another controversial topic in fitness circles and health communities. While some medical professionals highly recommend fasting, especially intermittent fasting, some experts depict reservations.
For example, this study titled “Fasting and exercise differentially regulate BDNF mRNA expression in human skeletal muscle” confirmed that BDNF gene expression was measured in human skeletal muscle following three intensities of exercise and a 48-hour fast while fasting upregulated BDNF by ∼3.5-fold.
According to another study, “neurobiological evidence suggests that the ketone metabolite β-hydroxybutyrate (BHBA) exerts many neuroprotective functions for the brain. The previous study revealed that BHBA could promote the expression of brain-derived neurotrophic factor (BDNF) at glucose inadequate condition.”
From my experience, intermittent fasting and long-term fasting with medical supervision provided me with significant physical and mental health benefits. In addition, reducing sugar intake helped me produce more β-hydroxybutyrate. In other words, I maintain ketosis allowing my brain to use ketones as an alternative source of energy. I shared my experience in these two articles.
3 — Reversing Insulin Resistance and Metabolic Syndrome
As this study informs:
“BDNF serves widespread roles in regulating energy homeostasis in both fetuses and adults, by controlling patterns of fetal growth, adult feeding, and physical activity, and by regulating glucose metabolism in peripheral tissues. Impaired BDNF signaling may be implicated in the etiopathogenesis of the metabolic syndrome.”
I posted several articles on insulin resistance, metabolic syndrome, and non-alcoholic fatty liver disease related to obesity, type two diabetes, and cardiovascular diseases. As they are comprehensive in scope, I link a few of the relevant articles as a reference to this point.
4 — Dealing with Chronic Stress, Inflammation, & Sleep Disorders
Chronic stress, inflammation, and sleep disorders play a critical role in physical and mental health, including neurodegenerative diseases.
As this study, published in Human Neuroscience, points out, “Yoga, Meditation and Mind-Body Health: Increased BDNF, Cortisol Awakening Response, and Altered Inflammatory Marker Expression after a 3-Month Yoga and Meditation Retreat”.
Sleep is critical for stress management and reducing chronic inflammation. In addition, some studies show an association between sleep and low levels of BDNF in the brain.
For example, this critical review points out that “poor sleep quality is related to alterations in the BDNF concentration. Some authors argue that most of the cases show that impaired sleep quality increases stress and, consequently, the vulnerability to depressive disorders, suggesting that there is a relationship between sleep, depression, and BDNF levels.”
As this is a broad topic, I link my articles related to stress, inflammation, and sleep for interested readers.
Conclusions and Takeaways
Our physical and mental health are closely linked. Therefore, for a sustainable and joyful life, we need to look after our mental health by reducing the risks of cognitive decline.
A well-known approach to reducing neurodegeneration is increasing and maintaining BDNF. This approach also helps create and maintain cognitive reserves as we age and contributes to high-quality longevity.
By adopting healthy habits and making lifestyle changes, we can naturally increase our BDNF.
Exercise, time-restricted eating, reducing chronic stress and inflammation, and improving sleep quality play an important role in increasing BDNF.
There is sufficient evidence that β-Hydroxybutyrate (BHB) contributes to BDNF and other cognitive capabilities. So, ketosis, naturally increasing BHB, is a compelling option.
Future articles will cover several other factors affecting BDNF, such as music, heat therapies (sauna), and neurobics (brain exercises).
As mentioned in this article, we can use everyday activities as brain boosters: Everyday Activities As Brain Boosters: How to use daily chores to boost our brainpower and reduce the chance of cognitive decline.
Here’s How I Activated Neurogenesis and Transformed My Depressive Mind into a Joyful One in 5 Steps.
Besides aiming to increase the hormonal intelligence of my readers and writing about neurotransmitters such as dopamine, serotonin, oxytocin, GABA, acetylcholine, and norepinephrine, one of my goals as a writer is to raise awareness about the causes and risk factors of prevalent diseases that can lead to suffering and death for a large portion of the population.
Thank you for reading my perspectives. I wish you a healthy and happy life.
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As part of my creative non-fiction writing goals, I’d like to share a few stories that might warm our hearts with a bit of humor into weighty topics.
Sample Humorous Stories
Finally, After Burning Her House, Georgia Found Enlightenment
Hilarious Tips to Prevent Brain Atrophy and Keep the Gray Matter Giggling
8 Psychological Points I Had to Unlearn and Relearn the Opposite
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