In the beginning came the cell, and the cell was without form and void. Except it was more specifically a nerve cell. A neuron. Which is pretty great, because we fuckin’ need those things.
Neurons are the cells that comprise the nervous system. These cells run the length of your body via pathways we know as nerves, connecting, or innervating your muscles and organs. In Yoga and Physiology, I discuss communication between major organs and the brain via the vagus. This is made possible by neurons.
We know that cells throughout our bodies are constantly being replaced. However, some cells are never replaced, and it was long believed that neurons were such cells. Generally speaking, neurons do not, in fact, proliferate: only owing to exceptions in some cases of injury and disease, the majority of neurons that comprise the nerves that snake throughout our bodies do not regenerate.6 However, there are areas in the brain where new neurons are born regularly. I’m going to focus on one area in particular, the hippocampus, and then discuss the implications of hippocampal neurogenesis as it applies to movement.
The Hippocampus, Hippocampal Neurogenesis, and Neural Plasticity
The hippocampus. This sliver of tissue is located just above the brainstem in an area of the brain known as the medial temporal lobe. And as small as it is, the hippocampus is “critical for learning, memory and cognition,”7 and as such carries much responsibility in our ability to recall events and understand where we are.
Recent work has shown that these cognitive functions — perception, imagination and recall of scenes and events — all engage the anterior hippocampus … specific substructures within the anterior hippocampus make critical contributions to episodic memory, imagination and visual scene perception. … We can vividly re-experience past events, simulate future events and imagine fictitious scenarios, in addition to experiencing the environment we currently inhabit. To achieve this, we must be able to construct internal representations of environments based on incoming sensory information and/or prior experience … there is evidence that structures within the medial part of anterior hippocampus have a role in constructing these representations.”7
The hippocampus also “plays an integral role in the consolidation of declarative memory, as well as context dependent and spatial learning processes in both humans and rodents.”1 Spatial cognition is how we mentally place ourselves and external objects in our environment, how we “construct internal representations of environments based on incoming sensory information and/or prior experience.”7 Recalling where our car is parked, where we live, and determining our proximity to another person, place, or thing are all products of spatial memory.
So, perception, imagination, recall of scenes and events, and spatial memory; these are all important capabilities in maintaining our autonomy – our independence, our freedom to live and move and do as we please. It is, then, in our best interest to keep the hippocampus in good working order.
One way our body does this is by a process called neurogenesis. Neurogenesis, also referred to as the neurogenic process, is the process behind newborn neurons and, as mentioned before, is not a prevalent process throughout the body. The hippocampus, however, is an exception. Now, there’s a whole thing about neuroblasts and mitosis and neural stem cells and such, but eventually we arrive at a point where a new cell exists and integrates into the existing brain structure:
“About 9000 new cells are generated each day in the rodent hippocampus … of which about 80-90% differentiate into neurons. Clinical studies have confirmed that similar processes also occur in the corresponding regions of the human brain … a recent study has revealed that approximately 700 new neurons are added to the adult hippocampus each day.”1,3
This is great news. Because neurogenesis is not a process undertaken by the majority of our nervous system, we assume our existing neurons live long lives. However, this is not the case with hippocampal neurons. We currently understand that there is a net loss of neurons as we age, though that loss is somewhat stymied by hippocampal neurogenesis: “We conclude that 0.004% of the dentate gyrus neurons are exchanged daily in adult humans,”3 the dentate gyrus being a structure of the hippocampus. These new neurons take on much of the work of their predecessors when integrated into the hippocampal formation:
“… there is evidence that they are recruited into hippocampal neuronal circuits known to be involved in spatial learning and possess particular physiological properties that make them more susceptible to behavioral-dependent synaptic plasticity. Thus, it is reasonable to speculate that these new neurons might be integral for hippocampal-dependent learning and memory, and in particular pattern separation.”1
New hippocampal neurons contribute to hippocampal function, with one added benefit: “newborn neurons have enhanced synaptic plasticity for a limited time after their differentiation, which is critical for their role in mediating pattern separation in memory formation and cognition.”3 Their susceptibility to behavioral-dependent plasticity will be explored another time. For now, let’s consider this concept of synaptic plasticity.
“Plasticity provides an organism with the ability to adapt to a changing environment. Under normal physiological conditions, plasticity promotes acquisition of new knowledge and skills.”4 As we learn, as we grow, our brain changes shape, and plasticity is the term used to refer to this process. To get more technical, plasticity refers to a connection between two neurons growing stronger (dubbed “long-term potentiation”) or weaker (dubbed “long-term depression”) depending on several factors. It is in the strength of these connections, or synapses, that makes it possible for us to learn and move.
In considering the synaptic plasticity of the hippocampus, “synaptic potentiation and depression sculpt the possibility of associations between stimuli such that learning, rather than giving rise to larger or smaller responses, enables one stimulus representation to evoke the memory representation of another.”5 How strongly our memories are created and retained depends upon the flexibility, or synaptic plasticity, of our hippocampal neurons:
”Adult-born hippocampal neurons have enhanced synaptic plasticity for a period of time after their differentiation. This, together with the dentate gyrus being a bottleneck in the network, allows a small proportion of neurons to have a substantial influence on the circuitry and hippocampal function. The new neurons are required for efficient pattern separation, the ability to distinguish and store similar experiences as distinct memories, whereas the old granule cells are necessary for pattern completion, which serves to associate similar memories to each other.”3
The old gradually makes way for the new while the new acquire responsibility from, and direct, the old. Furthermore, “numerous studies have suggested that neurogenesis in the [dentate gyrus] may play an important role in hippocampal-dependent learning and memory.”1 Given how frequently we process new memories, it is to our great benefit that hippocampal neurogenesis occurs, and that these new neurons have enhanced synaptic plasticity. The creation, retention, and recall of memories is, again, vital to our autonomy.
Now, why is any of this important? We can go our whole lives without caring about any of this information, right? … not really. You can be perfectly healthy throughout most of your life and then BAM! you start to lose your mind. Gradually at first, yet increasingly, you lose motor capabilities and your memory lapses. You’re later diagnosed with a neurodegenerative disease, and the outlook is bleak. Looking back on your life – assuming, of course, that you still have the mental capacity to do so – you wonder what you could have done to postpone or prevent the dementia you’re falling into.
Well, the answer is yes, there is. And the answer is obviously exercise – hence the title of this article. However, it’s good to know why. Why does your doctor keep prescribing exercise? While most health and wellness practitioners will prescribe exercise because of the benefits to your heart, there are further benefits of exercise that apply to your brain. Let’s take a look at some of the more prevalent neurodegenerative diseases and what each does to the brain, and then we’ll look at why exercise is effective in either slowing down their effects, or postponing or preventing their onset if undertaken early enough.
What are Neurodegenerative Diseases?
Generally, “adult neurogenesis is age dependent with the production of new neurons declining with age.”1 As mentioned earlier, neurogenesis does not completely replace the neurons that are lost. However, there are situations where neuronal loss comes at a much faster pace than normally experienced.
Just one look at the word “neurodegenerative” and you get an idea of what the primary problem is: a degeneration of neurons. Your neurons are dying off.
“Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease share the common characteristic of progressive loss of structure and/or function of neurons in the brain. Although neuronal degeneration affects specific neuronal populations … all these neurodegenerative diseases are characterized by a more or less severe loss of certain cognitive functions including learning and memory … it is speculated that cognitive decline in neurodegenerative diseases could be partly due to alterations in the neurogenic process.”1
Adult hippocampal neurogenesis is also altered during the course of these of diseases, which directly affects your ability to create, retain, and recall memories. We’ll look at the three major neurodegenerative diseases listed above, and what’s going on with hippocampal neurogenesis in each.
Alzheimer’s Disease is slow to come on, and resilient. It’s a progressive disease that slowly limits your cognitive abilities and motor skills, eventually resulting in dementia:
“At the pathological level, [Alzheimer’s Disease] is characterized by acetylcholine depletion, the accumulation of amyloid (or senile) plaques, and the formation of neurofibrillary tangles, which can lead to neuronal loss by apoptosis particularly in the cortex and hippocampus and severe brain atrophy.”1
Severe brain atrophy is kind of a big deal, considering we need the whole damn thing. While we may function after physical trauma to some parts of the brain, the extent to which Alzheimer’s erodes the brain makes this … difficult: “Alzheimer disease is characterized by progressive cognitive decline usually beginning with impairment in the ability to form recent memories, but inevitably affecting all intellectual functions and leading to complete dependence for basic functions of daily life, and premature death.”8
“Inevitably.” As unfortunate as it is, the truth is that no one comes back from Alzheimer’s. We are, however, learning more about the disease: “While the exact neurobiological mechanisms underlying the symptoms of [Alzheimer’s Disease] are still unclear, severe neuronal loss in areas of the brain involved in learning and memory, such as the hippocampus and prefrontal cortex, is evident in the [Alzheimer’s Diseased] brain.”1
Severe neuronal loss in the hippocampus suggests altered hippocampal neurogenesis. Part of the neurogenic process is the maturation of new neurons to take over the roles of dead and dying neurons. Whether or not the alteration of neurogenesis results in increased numbers of new neurons, “regardless of an increase in neuronal differentiation, the later stages of neuronal maturation during the neurogenic process might be compromised in the [Alzheimer’s Diseased] brain.”1 If the new neurons are incapable of fulfilling the role of late neurons, does it matter that the new neurons exist?
Parkinson’s is akin to Alzheimer’s in that motor control becomes deficient, and there is cognitive impairment. Parkinson’s, specifically, “is manifested by (1) severe motor symptoms characterized by a progressive impairment of movement control, akinesia, rigidity, and tremor; and (2) nonmotor symptoms such as cognitive decline, olfactory dysfunction, anxiety, and depression.”1
In regard to cognitive decline, Parkinson’s affects an area of the brain that feeds into the hippocampus: “[Parkinson’s Disease] is caused by death of dopaminergic neurons that project from the substantia nigra pars compacta to the striatum of the basal ganglia. … The neurogenic regions of the adult brain are innervated by dopaminergic projections from the [substantia nigra] and the ventral tegmental area” – neurogenic regions refers to the subventricular zone and dentate gyrus of the hippocampus – “therefore, the reduction of dopamine levels that occurs in [Parkinson’s Disease] may potentially affect the production of new neurons in the [subventricular zone and dentate gyrus].”1
Neurogenesis is extremely difficult to study in humans. What typically happens in many studies of neurological diseases is that patients’ brains are studied postmortem – diseased brain tissue is removed from the deceased patient and compared to healthy brain tissue. What studies have found in the case of deceased Parkinson’s patients are a reduction of particular cell types in the dentate gyrus of the hippocampus.1 This leads researchers to understand that this reduction is a “consequence of dopaminergic denervation of these neurogenic regions, providing further evidence of altered hippocampal neurogenesis in the human [Parkinson’s diseased] brain.”1 When we consider the decline of cognitive function as a symptom of Parkinson’s, altered hippocampal neurogenesis may very well be part of the cause.
Many symptons are shared between Alzheimer’s, Parkinson’s, and Huntington’s disease: “Motor disturbances, associated with the loss of voluntary movement coordination, are the classical symptoms of [Huntington’s Disease], with bradykinesia and rigidity appearing in later stages of the disease. Cognitive capacities are also severely affected during the course of the disease with the slowing of intellectual processes being the first sign of cognitive impairment … these cognitive impairments worsen over time and late-stage [Huntington’s Disease] patients show profound dementia.”1 However, Huntington’s disease has the additional unfortunate characteristic of being hereditable. While everyone carries the gene for Huntington’s, “only those that inherit the expansion of the gene will develop [Huntington’s Disease] and perhaps pass it on to each of their children,” (see hdsa.org for more information).
In terms of cognitive impairment and dementia – as discussed earlier – “it is speculated that cognitive decline in neurodegenerative diseases could be partly due to alterations in the neurogenic process.”1 Considering that dementia is a result of the onset of Huntington’s, we can deduce that the neurodegeneration occurs in areas of the brain that take a prominent role in memory formation and spatial reasoning (*ahem* the hippocampus). In the case of Huntington’s disease, while there is still much yet to be discovered, researchers are interested in the effects of neurogenesis as it relates to the disease, and we’ll see why as we get into our discussion on exercise.
That being said …
What’s movement got to do with it?
Movement, apparently, has much to do with it. Physical activity and exercise are proving to be appropriate therapies to prevent, delay, or improve the symptoms of cognitive decline in neurodegenerative diseases: “Physical activity has been repeatedly shown to improve cognition and prevent age-related cognitive decline in humans, particularly in individuals affected with certain neurodegenerative diseases. … physical exercise has emerged as the most effective, low-cost, and low-tech way for successful ageing, and therefore, it has the potential to represent a preventive or disease-slowing therapeutic strategy for age-related neurodegenerative diseases.”1
So movement improves cognition. How this happens is really interesting. There’s a protein dubbed Brain-Derived Neurotrophic Factor that “promotes the survival of nerve cells (neurons) by playing a role in the growth, maturation (differentiation), and maintenance of these cells.”9 Brain-Derived Neurotrophic Factor is vital to the development of neurons that result from hippocampal neurogenesis. When discussing Alzheimer’s, we saw that “later stages of neuronal maturation during the neurogenic process might be compromised.”1 Sounds like a job for Brain-Derived Neurotrophic Factor:
“Neurotrophins such as [Brain-Derived Neurotrophic Factor], insulin-like growth factor 1, and vascular endothelial growth factor have been recognized as primary mediators of adult neurogenesis. Age-related decline in neurogenesis has been associated with decreases in the levels of these trophic factors. Expression of [Brain-Derived Neurotrophic Factor] and [insulin-like growth factor 1] genes in hippocampal neurons has been shown in response to exercise training.”1
As levels of Brain-Derived Neurotrophic Factor decrease, so does the amount of neurogenesis that occurs. If movement increases the amount of Brain-Derived Neurotrophic Factor in the brain, then movement promotes the proper development of new neurons. Movement, then, becomes a viable method to treat neurodegenerative symptoms. “[Brain-Derived Neurotrophic Factor] is considered to be the most downstream factor mediating the upregulation of hippocampal neurogenesis by exercise … exercise training as a fitness intervention for the aging population effectively attenuates the age-related loss in hippocampal volume while also increasing serum levels of [Brain-Derived Neurotrophic Factor].”1
Furthermore, “optimization of [Brain-Derived Neurotrophic Factor] levels facilitates synaptic plasticity and remodeling, induction of long-term potentiation, modulation of gene expression for plasticity, resilience to neuronal insults, and alleviation of depressive symptoms.”10 Synaptic plasticity, we meet again. Brain-Derived Neurotrophic Factor, in facilitating synaptic plasticity, allows for the formation, retention, and recall of memories and events mentioned earlier. Turns out, movement allows you to maintain your autonomy a little bit longer, despite encroaching neurodegenerative symptoms.
Simply put, “physical exercise constitutes an effective intervention in neurodegenerative diseases, attenuating or limiting their progression.”2 And now we have an idea why.
Does the Type of Movement Matter?
“Exercise” and “movement” are a rather blanket term. Exercise can describe anything from brisk walking to handstands and backflips to weightlifting. Usually, however, when the term “exercise” is used, it refers to some sort of cardiovascular form of exercise – running, jogging, interval training, etc. Aerobic exercise is feasible and practical for Alzheimer’s subjects and has been shown to improve cognitive function. However, since Alzheimer’s is associated with low muscle mass and strength, muscle strength and power training can be crucial for Alzheimer’s patients. Balance training has been shown to improve the postural abilities of many who were moderately-to-severely affected by Alzheimer’s.2
So, aerobic exercise is good, but an all-inclusive training regimen is better: “Multicomponent exercise training [comprising balance, aerobic exercise (generally walking), and strength training] was shown to be particularly effective for improving postural and motor functioning and reducing the risk of falling in [Alzheimer’s Disease] subjects.”2
Furthermore, it appears the amount you exercise contributes to the prevention of neurodegenerative diseases: “Epidemiological data support an inverse relationship between the amount of physical activity undertaken and the risk of developing [Alzheimer’s and Parkinson’s] diseases. Beyond this preventive role, exercise may slow down their progression.”2
The more you move, the greater the preventative effects. As someone who may already be diagnosed with a neurodegenerative disease, the more you move, the slower the progression of the disease. Movement, then, serves us in more ways than just appearances: “regular engagement in physical exercise in midlife is associated with reduced risks of developing dementia later on in life, suggesting that physical exercise might indeed have preventative effects with regard to the development of age-related cognitive decline.”1
Despite some of the uncertainty regarding how these diseases progress, the underlying point should be clear: Get Moving. If spending a little bit of time each day in conscious movement – meaning not just walking to the kitchen for a glass of water but walking around the block for the sake of walking – can help prevent the onset of dementia, why not just do it? Doing a little bit of work every day now can save a lot of stress and effort later on.
And if you’re an individual who is currently dealing with a neurodegenerative disease, you now have a basis from which to work to stem the tide of dementia and maintain your autonomy for a while longer.
1Yau, S., Gil-Mohapel, J., Christie, B. R., & So, K. (2014). Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases? Retrieved January 10, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000963/
2Paillard, T., Rolland, Y., & Barreto, P. D. (2015, July). Protective Effects of Physical Exercise in Alzheimer’s Disease and Parkinson’s Disease: A Narrative Review. Retrieved January 10, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507374/
3Spalding, K. L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H. B., . . . Frisén, J. (2013, June 06). Dynamics of hippocampal neurogenesis in adult humans. Retrieved January 12, 2018, from http://www.cell.com/cell/fulltext/S0092-8674(13)00533-3
4Hays, S. A., Rennaker, R. L., & Kilgard, M. P. (2013). Targeting Plasticity with Vagus Nerve Stimulation to Treat Neurological Disease. Retrieved January 12, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615598/
5Takeuchi, T., Duszkiewicz, A. J., & Morris, R. G. (2014, January 05). The synaptic plasticity and memory hypothesis: encoding, storage and persistence. Retrieved January 19, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843897/
6Darian-Smith, C. (2009, April). Synaptic Plasticity, Neurogenesis, and Functional Recovery after Spinal Cord Injury. Retrieved January 21, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897707/
7Zeidman, P., & Maguire, E. A. (2016, March). Anterior hippocampus: the anatomy of perception, imagination and episodic memory. Retrieved January 22, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358751/
8Mayeux, R., & Stern, Y. (2012, August 01). Epidemiology of Alzheimer Disease. Retrieved January 23, 2018, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405821/
9BDNF gene – Genetics Home Reference. (n.d.). Retrieved January 23, 2018, from https://ghr.nlm.nih.gov/gene/BDNF
10Phillips, C. (2017, August 08). Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection. Retrieved January 23, 2018, from https://www.hindawi.com/journals/np/2017/7260130/
Featured and Header image by