Author(s): Mahsa AHMADI
Mentor(s): Dr. Robert J. Cressman, Department of Physics and Astronomy
AbstractThe glymphatic system or the clearing system in brain is a recent discovery that can lead to better therapeutic options for neurological disorders and better sleep. Previous studies show that the onset of the glymphatic system at sleep is accompanied by expansion of the extracellular space. However, there is no evidence of what parameter is shrinking to make the expansion possible. We hypothesized that this expansion is balanced with the shrinkage of neuroglia called astrocytes. We mainly focus on the role of Sodium Potassium Chloride Cotransporter 1 (NKCC1) in the astrocytes for a better understanding of how astrocytes swell during wakefulness and shrink during sleep. The research is based on a MATLAB computer model with ions conductance and derived dynamic parameters of neurons and the glymphatic system. After testing our hypothesis in the model on three different states, wakefulness, REM and NREM sleep, our results show that during NREM sleep the ECS volume increases and the volume of both neuron and glia increases. However, during wakefulness and REM sleep the ECS decreases and the volume in neuron and glia increases. Future studies in this field could lead to the development of improved therapeutic solutions for neurological diseases such as Alzheimer’s.
Audio TranscriptMentor information: Dr. Robert J Cressman, George Mason University.
Krasnow Institute George Mason University 4400 University Dr. MSN 2A1 Fairfax, VA 22032
Contact at [email protected]
This research was funded through OSCAR-URSP
My name is Mahsa Ahmadi and I’ve got a question for you.
How often do you get enough sleep? Have you ever wondered what happens during sleep that the lack of it can lead to several problems starting from feeling exhausted and less energetic during wakefulness?
The question to why we sleep and what changes happened during sleep is still not clear.
But in the recent decade, scientists discovered the glymphatic system, which is basically the brains cleaning system.
During sleep, the brain starts producing more CSF or cerebrospinal fluid, and washes off the harmful particles from the brain. Like bit amyloid proteins, the proteins involved in Alzheimer’s disease.
And then drains them out of the brain by a meningeal and cervical lymphatic vessels.
So why do we call it the glymphatic system? Because it comes from glia plus lymphatic system, glia being astroglia specifically because they allow the movement of fluid between the pair vascular spaces.
Water turns and thus are essential part of the glymphatic system.
During the transition of brain to sleep from wakefulness, scientists observed an expansion of the extracellular space, or the space surrounding the southern debris. Here, it’s shown in the red color. Now it makes sense, right? If you have more extracellular space, you can produce more fluid, which can flow easier and with less resistance, and thus.
Cleans the brain. The extracellular space is shown in red again in this fluid figure.
Now simple physics says that within a contained environment, if something becomes bigger, something else should become a smaller.
So for our studies include observation of expanded extracellular space, but not any observation of shrinking parameter.
That was when I and Doctor Cressman became interested to know what the shrinking parameter is and started our research funded through Oscar URSP.
We have noticed that it’s the astroglia that shrink during sleep and swell during wakefulness.
Used an existing computer model of a neuron and added a new mathematical equation for NKCC 1 or sodium potassium chloride cotransporter.
In astroglia this cotransporter leads to the uptake of potassium ions, accumulation of chloride and swelling.
Now, in order to compare the volume change within different states like wakefulness, REM, and NREM sleep, we coded for neurons to fire at certain frequencies equal into those seem naturally during those states.
For example, during NREM sleep the frequency of the slow delta waves is between .5 to 4 Hertz. So we coded for that frequency in our model and then looked for the corresponding volume changes.
According to our results, during non-REM sleep.
The extracellular space increases while both glia and Nora and decrease in volume. However, during Ram and wakefulness states, the extracellular space decreases, and glia and neuron increase in volume.
It also makes sense that when the extracellular space is shrinked during wakefulness, as a result of that shrinkage, the concentration of potassium outside increases and that leads to neurons becoming more excitable and getting it faster rates.
It’s also interesting to know that even sub threshold stimulations and our model caused volume change in glia neuron and extracellular space.
Why is this research important? Because knowing more about the changes that happen in the brain during the glymphatic system can help us come up with better therapeutic options for diseases that depend on the proper functioning of the glymphatic system like Alzheimer’s.
Suggestion for future research would be looking for that factors that lead to that volume change and their mechanisms, but until then, please make sure you get quality enough sleep. Thank you.
How often do you get enough sleep? Have you ever wondered what happens during sleep that the lack of it can lead to several problems starting from feeling exhausted and less energetic during wakefulness?
The question to why we sleep and what changes happened during sleep is still not clear.
But in the recent decade, scientists discovered the glymphatic system, which is basically the brains cleaning system.
During sleep, the brain starts producing more CSF or cerebrospinal fluid, and washes off the harmful particles from the brain. Like bit amyloid proteins, the proteins involved in Alzheimer’s disease.
And then drains them out of the brain by a meningeal and cervical lymphatic vessels.
So why do we call it the glymphatic system? Because it comes from glia plus lymphatic system, glia being astroglia specifically because they allow the movement of fluid between the pair vascular spaces.
Water turns and thus are essential part of the glymphatic system.
During the transition of brain to sleep from wakefulness, scientists observed an expansion of the extracellular space, or the space surrounding the southern debris. Here, it’s shown in the red color. Now it makes sense, right? If you have more extracellular space, you can produce more fluid, which can flow easier and with less resistance, and thus.
Cleans the brain. The extracellular space is shown in red again in this fluid figure.
Now simple physics says that within a contained environment, if something becomes bigger, something else should become a smaller.
So for our studies include observation of expanded extracellular space, but not any observation of shrinking parameter.
That was when I and Doctor Cressman became interested to know what the shrinking parameter is and started our research funded through Oscar URSP.
We have noticed that it’s the astroglia that shrink during sleep and swell during wakefulness.
Used an existing computer model of a neuron and added a new mathematical equation for NKCC 1 or sodium potassium chloride cotransporter.
In astroglia this cotransporter leads to the uptake of potassium ions, accumulation of chloride and swelling.
Now, in order to compare the volume change within different states like wakefulness, REM, and NREM sleep, we coded for neurons to fire at certain frequencies equal into those seem naturally during those states.
For example, during NREM sleep the frequency of the slow delta waves is between .5 to 4 Hertz. So we coded for that frequency in our model and then looked for the corresponding volume changes.
According to our results, during non-REM sleep.
The extracellular space increases while both glia and Nora and decrease in volume. However, during Ram and wakefulness states, the extracellular space decreases, and glia and neuron increase in volume.
It also makes sense that when the extracellular space is shrinked during wakefulness, as a result of that shrinkage, the concentration of potassium outside increases and that leads to neurons becoming more excitable and getting it faster rates.
It’s also interesting to know that even sub threshold stimulations and our model caused volume change in glia neuron and extracellular space.
Why is this research important? Because knowing more about the changes that happen in the brain during the glymphatic system can help us come up with better therapeutic options for diseases that depend on the proper functioning of the glymphatic system like Alzheimer’s.
Suggestion for future research would be looking for that factors that lead to that volume change and their mechanisms, but until then, please make sure you get quality enough sleep. Thank you.
3 replies on “Shrink to Clean: Exploring the Glymphatic System and Volume Change in Brain”
Hi Mahsa,
Thanks for sharing your project. I didn’t realize that so much of the brain’s functioning relied on fairly predictable physics.
I was wondering, how did you/ your research team come up with the equation needed to change the computer model to fit your experiment?
Hi,
thank you very much for your comment and question.
We combined Hodgkin-Huxley equations and assumed that in a steady state the total of currents sums to zero, and that gave us an equation for NKCC1 (Sodium Potassium Chloride Cotransporter 1).
Great project and excellent presentation. I am wondering about the narrowing of extracellular space during REM sleep. I would have expected the opposite, since REM sleep is thought of as good quality sleep. So much we don’t know about the brain.