Erin Merritt
Over time, the body’s cells stop working and die. When cells of the nervous system called neurons die, they damage and even destroy parts of your nervous system, which is most well known in the brain. But did you know that neurons can also be found in and eventually die and impact the function of your limbs and even your gut?
Dr. Bhupinder Vohra is a principal scientist at MRIGlobal is one of the world’s leading experts on the functions of the nervous system and what happens when it doesn’t work like it should. On this episode – Neurodegeneration – how our nervous system functions like an electrical grid, nature’s impact on the nervous systems of the living and the unborn, and where you might first experience signs of neurodegeneration. I’m Erin Merritt and this is Science Diction from MRIGlobal.
Bhupinder Vohra, PhD
When we think about the nervous system, we usually think about brain and the spinal cord, but brain and spinal cord are only part of the nervous system that we call the central nervous system. Then we have a whole branch of nervous system, what we call the peripheral nervous system. That actually is the main part of the nervous system that allows your brain to work, comprehend the environmental information and respond to that information that is essentially for our survival.
Erin Merritt
Tell me about the nervous system. How does it work?
Bhupinder Vohra, PhD
Nervous system is a complex network of specialized cells called neurons and the glial cell, and by an estimate, an adult human has almost 86 billion neurons. You can consider each neuron as like electric grid where you have the transformers and the wires. So when we think about the nervous system as a whole, so we can see that all the neuronal cell bodies, they’re essentially located in the brain and the spinal cord. And then what is in your limb and the rest of the body, those are essentially the wires. Those wires are bringing signal from the body to the spinal cord and from spinal cord, that signal is going to the brain. In some cases, these wires, for example, in cranial nerve, they can directly go from, for example, from your eyes or nose or ear directly to the brain. So essentially the signal is going through the wires, what we call nerves, to the brain and the spinal cord.
Erin Merritt
That’s a great description. And what happens when portions of the nervous system fail?
Bhupinder Vohra, PhD
Oh, there can be many things that can happen. You’ll not be able to swallow the food, cannot breathe, cannot walk, and people can lose sensation. You cannot feel touch, you cannot feel heat or cold. So various deleterious effects can happen because the nervous system is not functioning properly.
Erin Merritt
And what prompts these failures?
Bhupinder Vohra, PhD
Oh, there can be multitude of things that can cause these failures. For example, brain injury, stroke, deficiency of vitamins, toxins, infections, and pesticide exposure. So many environmental factors, along with the genetic predisposition.
Erin Merritt
So are there common mechanisms between the peripheral and central nervous system neuropathies?
Bhupinder Vohra, PhD
Yes. So the basic mechanism of degeneration in the peripheral nervous system and the central nervous system are same. They both involve activation of glial cells. They both involve degeneration of cell body, what you call transformer as well as the wires. So in terms of when you talk about individual cell in the brain, so the neuron has a central cell body and long fiber, what we call axon and other fiber, what we call dendrite. So essentially the dendrite receives the information and brings it to the cell body and that information is processed in the cell body and travels through the axon to the target. So both the cell body as well as axon can degenerate. So like I give an example of the electric signal, depending upon the type of degeneration, you can have either wire set on the fire first or the transformer blown up the first, so we have to think about from where this degeneration is starting and that can be the key to target the therapy for a particular neurogenerative disorder.
If we talk about peripheral nervous system, these are all wires. For example, in diabetes, people lose sensation of touch. Even in Parkinson’s also the wires are caught on fire first. So there are very common mechanisms in both peripheral and the central nervous system neurodegenerative disorders.
Erin Merritt
That makes sense. I think most people are probably familiar with diseases like Alzheimer’s, ALS, or Parkinson’s. Are those the most common examples of neurodegeneration?
Bhupinder Vohra, PhD
This is an excellent question actually. When people talk about neurodegeneration, they think about these three diseases because these are most talked about neurological disorders. But I will give a context. So in the United States, around six million people are suffering from Alzheimer’s. Around one million people are suffering from Parkinson’s. And similarly, around one million people are suffering from ALS, whereas 20 million people in the United States are suffering from peripheral neuropathies. And around 28 percent of the people who are diabetic, they are suffering from peripheral neuropathy. 30 to 60 percent of the patients who undergo chemotherapy, they suffer from peripheral neuropathy. It is only what is discussed more that people know more about, for example, Parkinson’s, Alzheimer’s, but peripheral neuropathies are way more common than these disorders.
Erin Merritt
That’s really interesting. Why do you think that is?
Bhupinder Vohra, PhD
So for example, with the advent in good health technology, people are living more so that means that aged people are getting more of those disorders. For example, if I say Alzheimer’s before President Reagan, nobody knew what Alzheimer’s is. When famous people get the disease in the old age, it’s more common.
Erin Merritt
I think that helps make it tangible for people to understand.
Bhupinder Vohra, PhD
Right. And the other thing is the Alzheimer’s and Parkinson’s also, these are called progressive neurodegenerative disorders. That means they start very early, but they develop slowly and you see the symptom very late in the life instead of when they started. So someone initially they start forgetting names and then later they start forgetting whether they eat food or not. Later they even stop recognizing you. So that kind of stepwise progression, people are more looking toward that, making it more dreadful thing like you started forgetting names and now you don’t remember your relatives. So that’s why people really think about those diseases in that context.
Erin Merritt
Though many people might think of neurodegeneration as only a function of the brain or extremities, as that’s where symptoms might be most obvious, you might be surprised to learn where some symptoms are first found.
Bhupinder Vohra, PhD
One of the most common thing in all those neurodegenerative disorders is that all these people who are suffering from these disorders, most of those have severe gastrointestinal issues. So even before you start seeing the tremors in the hand in Parkinson’s or you start see any effect of chemotherapy, most of these patients are constipated and actually constipation is way before, say in early 30 or 40 years of age, you can have constipation in a Parkinson’s patient, while the motor symptom will appear way later in the lifetime.
Erin Merritt
That’s fascinating.
Bhupinder Vohra, PhD
You will say then, “Why they are constipated? What happens?” Actually, before anything happens to the central nervous system? There is a nervous system in the gut, what we call enteric nervous system, that is also called second brain actually. And the neurons of that nervous system start getting degenerated before anything happens to the central nervous system. Now, some theories also say that the pathological protein actually travel from the in nervous system via vagus nerve to the central nervous system. Now there are some studies telling also that some of these pathological protein, they can even come from central nervous system and move toward the enteric nervous system as well and what we call it gut brain access. So now it is believed that before anything happens to the central nervous system, the enteric nervous system actually starts showing the symptom of those disorders. And that is very common even for the people who are drug addicts. Most of those people are constipated because they have issues with the nervous system in the gut. So gut is probably the other organ which is kind of ignored, but the nervous system of gut is affected and can be an early indication of various neurological issues in the body.
Erin Merritt
So how does that work?
Bhupinder Vohra, PhD
Say for example, Parkinson’s, how many people we can relate with the genetic mutation who have Parkinson’s? Only five to 10 percent. So say around 90 percent of the patients, they don’t have any known mutation, but they still have symptoms of Parkinson’s, what we call idiopathic Parkinson’s. So it is believed that various environmental factor and specifically the toxins, those can be pesticide, those can be fungicide, or those can be herbicide. Once they are going in the gut, they are actually causing issues in the gut nervous system.
These pesticides, for example, rotenone, permethrin, they’re all correlated to the Parkinson’s with epidemiological studies. And actually there was a recent study last year actually in May So they have studied almost 288 pesticides in California valley. And what they found, 50 of those pesticides were actually linked to Parkinson’s. And surprisingly, most of those pesticides are still used in United States and Europe. And similarly, they were able to find out some fungicide, some herbicide, they were related to Parkinson’s. So exposure to these toxins causes the degeneration and that can lead to various neurological disorders, including Parkinson’s.
Erin Merritt
You mentioned these gut issues occurring in adults starting in their thirties and forties. Are there other symptoms that can start earlier?
Bhupinder Vohra, PhD
Oh yeah, that’s a really interesting question. So think about how do we know about Parkinson’s? How do we know about Alzheimer’s? We know it because those happening to the adults or the older people, even diabetic neuropathy. But now I’m going to tell you another disease that is called Hirschsprung’s disease or megacolon. That disease is actually very common. One in 5,000 live born babies are actually born with that disease.
These babies are born without the neuron in the distal part of the gut. And the gut neurons, or the nervous system of the gut, is responsible for the gut motility as well as secretion and absorption that is happening in the gut during digestion of the food.
So the food at that time, the milk early baby, they’re drinking, they cannot pass down the gut. So what happens, their belly distends, they start vomiting, bilious vomiting, bloody vomiting, and these kids die newly born baby. So this is a devastating disorder, but that’s actually a very common problem of the enteric nervous system.
Erin Merritt
Are these many symptoms then predictive of future central nervous system issues?
Bhupinder Vohra, PhD
So Hirschsprung’s disease is a disease that start right at the birth, so that’s very different. But in Parkinson’s, these people are constipated years before you see the motor symptom. So yes, the symptoms in the gut can be indicative of the future center nervous system disorders.
Erin Merritt
So earlier you mentioned neurodegenerative diseases that are associated with age. As the global population age increases, are we seeing these issues more often?
Bhupinder Vohra, PhD
Yes, that’s true because these neurological disorders are progressive. That means they start very early, but the symptoms are manifested very late. So as the medical facilities are increasing, people are living longer life. So that means more peoples are manifesting these neurological disorders. And so that means that with aging population, we’ll see more and more people who are experiencing symptom like Alzheimer’s or the Parkinson’s.
Erin Merritt
Do you think that’s a function of the environment they’re in or are some people more predisposed due to genetics?
Bhupinder Vohra, PhD
Yes, it can be function of both genetics as well as the environment. But for most of these neurological disorder, especially for Parkinson’s, you cannot explain all the patients based on their genetics. So it’s the predisposition to the environment. For example, lack of certain vitamin means in the vitamin B categories, exposure to toxins, exposure to pesticides, all those things can be linked to the neurogenerative disorders.
For example, people working in the farms who are more exposed to these pesticide or fungicides, they’re more prone to get these disorders.
Similarly, in the Vietnam War, they started using Agent Orange as an herbicide. And now that is one of the causal factor for the Parkinson’s Disease. So you can think about those soldiers who were in contact at that time, they got Parkinson’s. So it’s all environment dependent.
Erin Merritt
What research is being done today to address these issues?
Bhupinder Vohra, PhD
People are actually targeting neurological disorders now in a very different way. So in the past, people were thinking if a group is studying Alzheimer’s, they’re only talking about Alzheimer’s. They’re not worried about what is happening in ALS or Parkinson’s. So now people are understanding that there are common mechanisms for these neurogenerative disorders, so people are collaborating more. And the second thing is happening, although we have learned a lot from animal models, but animal models have not actually provided us great breakthroughs in these research areas. And we know that 90 percent of the studies done on the animal models do not translate to the human. So people are actually trying to move from animal models to the models which are actually replicating the human physiology. And people are actually trying to go to organal culture or what we call microphysiological systems to study and understand the diseases and trying to unravel the mechanism of these neurodegenerative disorders so they can think about devising better pharmaceutical agent to treat these disorders.
Erin Merritt
So this is a pretty heavy conversation topic and obviously there’s not one answer for everything in some of the research is more depressing than uplifting. What keeps you invested in the work and are there signs for hope?
Bhupinder Vohra, PhD
Yes, there is a lot of hope, but think about when we talk about someone, when we ask some person “What is the difference between living and the dead?”. Usually people talk about living things can reproduce, but think about what keeps you living. What keeps you living is how you respond to your environment. You can feel cold, you can feel hot, you can feel hunger, you can see. What control all those things is your nervous system. So that particular information, that nervous system is the key for our survival, always motivates me as well as the other people who are doing the nervous system research. And with the advent of new microphysiological system, we know we can actually mimic human physiological systems right in the dish. So there are hope that we’ll learn more about human disease, we’ll learn more about the mechanism. And that will be a big step in understanding and devising pharmaceutical strategies for neurological disorders.
