The Link to Exercise and Neurological Disease – Potential Preventer?

             Neurological diseases, such as Alzheimer’s disease, affects the human population with no curing treatments in sight. This disease causes debilitating symptoms – such as progressive memory loss and loss of brain function – to occur in people, and they are hard to understand by scientists in terms of finding efficient treatment and prevention options. However, there may be a method to improve memory and increase neuron production to help neurological brain function in patients with Alzheimer’s or progressing dementia. This method, exercise and movement, may also be a preventative method through increasing the production of brain-derived neurotrophic factor (BDNF), a known molecule that is involved in improving memory and increasing neuronal production (NYU Langone Medical Center, 2016).

            In the article, “Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer’s disease”, Krishna Bharani and colleagues show the relationship between BDNF levels in the brain and the pathogenesis and progression of Alzheimer’s. They looked into the expression of TrkB receptors in the brain, the main receptor for BDNF, and the tissue levels of BDNF forms pro-BDNF and mature BDNF. After looking into the brains of humans that had severe Alzheimer’s disease, they found that pro-BDNF levels in different cortices of the brain were lower in the Alzheimer’s brains versus normal brains. BDNF in the cerebrospinal fluid was also found to be lower, along with the lowered expression of TrkB receptors and pro-BDNF in the hippocampus, the main learning and memory center of the brain. These levels all correlated with increased serum BDNF levels and staining of amyloid plaques in the brain – one of the main causes of Alzheimer’s disease. This serum BDNF could be due to the increasing neuroinflammation found in Alzheimer’s.  Also, reduced levels of total BDNF, found in the cortical regions of the brain, correlated with the increased presence of amyloid plaques. These results show that BDNF levels and expression of TrkB receptors in the brain are directly correlated to the pathogenesis of Alzheimer’s disease in an inverse proportion: decreased levels of BDNF and TrkB receptors lead to the increased production of amyloid plaques and progression of Alzheimer’s disease. This relationship between BDNF levels and the pathogenesis of Alzheimer’s can be used to potentially create treatments to help reduce symptoms of the disease. 

            In the article, “Mice on wheels show scientists how exercise benefits their brains”, the scientists at the NYU Langone Medical Center focus on how exercise could potentially be used as a treatment to defend against and prevent neurological diseases. When looking in mice and subjecting them to exercise, they found the increased production of BDNF in the hippocampus, which is known for its role in improving memory and increasing the production of neurons in the brain. BDNF could be a potential protector for the brain and could potentially reduce related symptoms of Alzheimer’s disease – memory loss and brain function loss, as it has been found to lower dementia rates. Another finding when looking at these rats was increased production of beta-hydroxybutyrate (DBHB) in the hippocampus, a naturally occurring ketone that has a role in triggering the biological reactions that activate BDNF production, and they found that DBHB also prevents the suppression of BDNF production in the brain by preventing histone deacetylase complexes (HDACs) from working – it performed the same function of known HDAC inhibitor drugs. They performed their study by comparing the brains of mice that ran in cages for a month versus ones that did not. They performed chemical analyses to determine BDNF production when exposed to the HDAC inhibitors and DBHB and performed gene testing to determine the activeness of genes. This study highlights and shows that BDNF and DBHB treatments could be potentially used to treat Alzheimer’s disease to reduces symptoms, but the main point is that exercise could potentially be used in a preventative way to protect the brain from neurological diseases or as a therapeutic treatment method to help reduce the memory and increase brain function through the naturally increased production of BDNF and DBHB.

            Alzheimer’s disease at this moment in time is an incurable disease that causes debilitating symptoms in humans – leading to the total loss of brain function and complete memory loss. Potential treatments have been explored to try and reduce amyloid plaques in the brain – the main causes of Alzheimer’s – but these efforts have been futile at this point. Until that treatment has been developed, further treatment methods have to be produced to try to reduce symptoms and prolong the life of Alzheimer’s patients. Here comes in BDNF, a protein molecule in the brain that has been linked to dementia and Alzheimer’s disease – where decreased production of this protein leads to further progression of the disease, as shown in Bharani et. al. Through the scientists at NYU, it has been found that increasing BDNF and DBHB production in the brain through exercise could potentially be used to defend the brain and protect it from neurological diseases, and it could possibly be used as a preventative treatment of Alzheimer’s. It has also been found that it could be as a treatment to manage early Alzheimer’s, as BDNF has been linked to the hippocampus and has also been linked to having a role in improving memory and neuronal production in the brain. Through studies like this and others, BDNF’s role in the brain may be able to be used for our benefit, and it could possibly lead to treatments of untreatable neurological diseases, such as Alzheimer’s disease.

 

 

 

References

 

Anand, Kuljeet Singh, and Vikas Dhikav. “Hippocampus in health and disease: An overview.” Annals of Indian Academy of Neurology vol. 15,4 (2012): 239-46. doi:10.4103/0972-2327.104323

 

Bharani, Krishna L et al. “Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease.” Neurobiology of agingvol. 87 (2020): 49-59. doi:10.1016/j.neurobiolaging.2019.11.010

 

NYU Langone Medical Center / New York University School of Medicine. "Mice on wheels show scientists how exercise benefits their brains: Running rodents make more of 'Miracle-Gro' chemical for the brain." ScienceDaily. ScienceDaily, 2 June 2016. <www.sciencedaily.com/releases/2016/06/160602083254.htm>.

 

Sama F Sleiman, Jeffrey Henry, Rami Al-Haddad, Lauretta El Hayek, Edwina Abou Haidar, Thomas Stringer, Devyani Ulja, Saravanan S Karuppagounder, Edward B Holson, Rajiv R Ratan, Ipe Ninan, Moses V Chao. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. eLife, 2016; 5 DOI: 10.7554/eLife.15092