Astrocytes: More Than Just Cells
Introduction:
There are hundreds of thousands of nerves and cells throughout the human body, all of which are in our body because they serve a purpose in our survival, body function, or body structure. Many thousands of neurons are connected in webs that make up the human brain, and are vital to thought, sight, movement, and memory, among other things. When they were first discovered, scientists thought that the star-shaped cells were only there to fill gaps between important neurons. However, this assumption has been proven incorrect. Astrocytes play a huge part in the creation of long-term memories in the human brain. Since being discovered, biologists have found that humans also have astrocytes in their spinal cords. Through many tests and discoveries, biologists have found a connection between astrocytes and Amyotrophic Lateral Sclerosis (ALS).
Findings:
When scientists first came across astrocytes, they thought the purpose of an astrocyte was to keep important neurons in place and to fill gaps between neurons (Lyons 2011,38). Because astrocytes are non-electrical brain cells, scientists thought that they could serve almost no other purpose (Akst 2010, 10). Scientists have known for many years that voltage changes and synapses are important to memory formation, but now we know that astrocytes are there to help complete the process by giving a burst of energy to move the process along (Akst 2010, 11). There may not be any electrical charge, but there is lactate. One of the first things Scientists looked for when studying astrocytes was if lactate was present. Lactate is an energy source that is derived from the glycogen the body produces from stored glucose (DeMarco 2011, 30). Lactate is essential because it is the fuel source for astrocytes. When presented with too little lactate, astrocytes do not function properly and a person will find it difficult to retain memories.
A biologist named Alberini found that there was a difference between creating short-term and long-term memories. Alberini did many test runs with rats and she found that to achieve short-term memory, the body has to make changes to the already present proteins (DeMarco 2011, 34). Long-term memory, on the other hand, has to undergo protein synthesis and changes in the gene expressions, which changes the whole structure of the synapses (DeMarco 2011, 34). Alberini ran tests on rat memory, and found that an avoidance behavior, such as teaching a rat not to go into a certain area through electric shock, was a way to measure memory. She said that “[w]hen events are emotionally charged, we remember them much better” (DeMarco 2011, 33). The electric causes the mouse pain, and so if it avoids that area, there is no pain, that’s how an electric shock is emotionally charged.
The same concept of emotionally charged events was used in another experiment where rats were given a foot shock before being injected with a blocking agent as a way to test memory loss. A scientist would then take a rat and block the glycogen breakdown that the body performed with an injection to the brain. This was done in order to cause amnesia (Blanchard 2011, 23). Some of the rats the scientists used received just the blocking agent, while others were injected with a mixture of the blocking agent and lactate, so the biologists could see how the combination would affect the long-term memory of the rats (Blanchard 2011, 24). This test resulted in two things happening: the rats that had been given the regular blocking agent experienced long-term memory loss and the rats that were injected with the agent and lactate mix were showing no memory impairment (Blanchard 2011, 24). The lactate and blocking agent combination reacted in a way that kept the rats memory normal. However, the lactate that the body produces on its own wasn't enough to overpower the blocking agent, as was proven by the fact that those rats given only the blocking agent lost their memories.
In keeping with the research found on the links between long-term memory and astrocytes, another study that was conducted by Alberini and colleagues is similar, yet proves a different point all together. This study reports that the glycogen breakdown and lactate release to astrocytes is only essential to long-term memories, not short-term (Suzuki, Stern, Bozdagi, Huntly, Walker, Magistretti, and Alberini 2011, 26). The fact that glycogen breakdown, and lactate release is not needed for short-term memory formation raises the thought that maybe short-term memories are either easer to create, or because they are short-term, the lactate transfer does not have time to settle and make it a long-term memory. If one were to disturb the expression of the lactate transporters Monocarboxylate Transporter (MCT4) or Monocarboxylate Transporter MCT1, it will cause amnesia(Suzuki, Stern, Bozdagi, Huntly, Walker, Magistretti, and Alberini 2011, 26). Amnesia, it seems, is the one thing that the researchers always try to avoid, but the one thing that always comes up. Long-term memory potentiation (LTP) impairment is saved by L-lactate but not equicaloric glucose, just like the monocarboxylate transporters are saved by both of those (Suzuki, Stern, Bozdagi, Huntly, Walker, Magistretti, and Alberini 2011, 26).
So, in a sense, LTP and monocarboxylate transporters are the same, in that the chemicals that saves the LTP and the monocarboxylate transporters from amnesia formation. Both Glycogenolysis and Astrocytic lactate transporters are critical to the process of the introduction of molecular changes that are required daily for memory formation. Lactate does not do all of the work (Suzuki, Stern, Bozdagi, Huntly, Walker, Magistretti, and Alberini 2011, 27). Though this study goes deeper into the behind-the-scenes aspects of the creation of long-term memory formation, it still concludes the same point, that astrocyte-neuron lactate transport is still required for long-term memory formation (Suzuki, Stern, Bozdagi, Huntly, Walker, Magistretti, and Alberini 2011, 28).
Although there are many thousands of astrocytes in the human brain, there are equally as many in the spinal cord. In one experiment, scientists took human astrocytes generated from stem cells that were called fetal glial precursor cells and isolated them (Kaiser 2011, 5). The biologists then took the now isolated cells and exposed them to signaling molecules that were used to switch on or off signals in the cells, eventually creating two types of human astrocytes (Kaiser 2011, 5). Due to the exposure, the cells were made into Bone Morphogenic Protein (BMP) and Ciliary Neurotrophic Factor (CNTF) human astrocytes, and injected them into injured rats to see which one would respond, and aid the recovery of the spinal cord (Kaiser 2011, 6). The BMP astrocytes were remarkable and provided up to a 70 percent increase in the protection of the injured neurons in the spine, which ended up helping the nerve fiber growth and helped to restore the rat’s locomotive functions (Kaiser 2011, 7).
A new study shows that if a scientist were to combine partially differentiated stem cells with gene therapy, it could put forward a cushion around the damaged nerve fibers in the spinal cord of rats (Unknown 2011, 40). This is used to mimic the actions of two nerve growth factors, and improve the rat’s motor functions, as well as the electrical transfer to both the brain and leg muscles (Unknown 2011, 40). The stem cells that were used came from two kinds of glial cells: astrocytes, which help support and influence the activity of neurons, and also oligodenrocytes, which produce melanin (Unknown 2011, 42). Many scientists have found through their research that there may be a connection between the way both the spinal cord astrocytes and the astrocytes found in the brain function, and Amyotrophic Lateral Sclerosis (ALS).
ALS, also known as Lou Gehrig's disease, is a neurodegenerative disease that really disrupts and affects the nerve cells progressively (Unknown 2010, 46). Everything in the body is connected, and the brain and pine are the two main parts that make up the human nervous system, which is connected to everything else. Unfortunately, the progression of the disease leads to the degeneration of the motor neurons, eventually leading to death (Unknown 2010, 47). Findings reveal that astrocytes may engage in the specific degeneration of motor neurons connected to ALS (Nagai, Re, Nagata, Chalazonitis, Jessell, Wichterle, and Przedborski 2007, 4). Within the short time it takes the motor neurons to advance through the stages of ALS, they are no longer able to send out any more impulses to the muscle fibers that usually work to control movement (Unknown 2010, 48).
We know so much about both ALS and astrocytes separately, but it is only recently that we have discovered that there is a connection between the two. In one study, ALS evidence has shown that dysfunctional astrocytes may be a contributing player in the progression of the disease (Patoine 2007, 16). Glutamate is a neurotransmitter that regulates nerve firing. Too much Glutamate is lethal to the nerve cells (Patoine 2007, 17). Astrocytes are available to clean up the excess glutamate, regulating it to make sure that the levels of glutamate in the system do not reach lethal levels of concentration (Patoine 2007, 18). Lactate has always been thought of as a primary source of fuel for neurons, in the study the team conducting this experiment saw that there was a similar disappearance of astrocytes to transporters as there was glutamate transporters to astrocytes (Patoine 2007, 18and 19). The team observed that the lactate transfers to the astrocytes were nonexistent, and due to the fact that lactate transfer to the astrocytes is a critical part in the supply chain, this was a problem (Patoine 2007, 19). All of this research links back to ALS because it shows us that there is a link between the test results for rats and for human ALS patients. These studies really show us how dysfunctional astrocytes have a connection to the ALS process, and get us closer to a cure.
In a different study, scientists found that mutant proteins and the gene Superoxide Dismutase (SOD1) played a part in the link between astrocyte function and ALS. In the tests, they found that that astrocytes that carry a mutated form of an ALS forming protein, kills the motor neurons (Unknown, 2007, 44). Due to this, the replacement neurons that were created by the stem cell therapy would be damaged (Unknown 2007, 44). ALS starts by deteriorating the nerve cells within the body until the cells die, then the victim of this disease becomes paralyzed, and eventually dies. This disease causes a slow, horrible death, and unfortunately people are diagnosed with ALS all the time. Through the tests conducted, the scientists found that SOD1 is the cause of some ALS cases, and that progressive degeneration of the body’s motor neurons leads to paralysis and death (Unknown 2007, 45). The astrocytes that showed mutant SOD1 and co-cultured with motor neurons degenerated and killed the neurons However, SOD1 in neurons, fibroblasts, or even microglia did not cause neuronal death (Unknown 2007, 46).
More recent studies have uncovered more about the connection between SOD1, ALS and astrocytes. If a researcher takes SOD1 ALS mice, he or she can alter some cell lines, in efforts to rid the mice of the SOD1 mutation (Halfin 2010, 1). Turning off the SOD1 is done by giving the mice healthy SOD1 to counterbalance it (Halfin 2010, 2). The mutation doesn’t mean that the mice cannot get sick, turning off the SOD1 delays it, but just as any other sickness, once symptoms start to show, they will progress at a normal rate (Halfin 2010, 2). However, if a researcher turns off the SOD1 mutation in the astrocytes, the symptom onset becomes the same as in normal SOD1 mice, but the difference is that the progression is slowed down, and the mice get to live a longer life (Halfin 2010, 2).
Conclusion:
In conclusion, astrocytes are much more than once thought. Astrocytes, in the human brain, work to produce long-term memories while using lactate as a power source. The restriction of lactate has been shown through studies to cause memory loss, both short-term and long-term, in rats. Thanks to the breakthrough of stem cell research, scientists have discovered ground-breaking treatments that will benefit the people with ALS. The knowledge gained from all of the research by scientists, has lead us into new medical findings and we will continue to gain more knowledge of the horrible condition of ALS. It is through many years of testing and understanding that we, as a nation, can give healthier lives to the next generation. Unfortunately, we are still many years away from actual human testing, but thankfully, we are on the right path. So when it all comes down to it, we should really thank the men and women conducting these studies, because those are the people who are making our knowledge of the human body that much bigger, one astrocyte at a time.