1. 11:52 30th Jan 2012

    Notes: 73

    Stress and Memory Cortisol is another hormone released by the adrenal glands during stress.  Cortisol is more of a long-term stress hormone, as it is not immediately released during stress (like epinephrine/adrenaline), but if the stress is severe enough or long-lasting, it will be.  Cortisol seems to prevent encoding of new memories as well as memory retrieval.  In every day life, this can have big effects on exams for college students… the more stressed they are, the more difficult it will be to form and retrieve the information they have studied.  In other situations, this might be a good thing.  It is thought that this might also be driven by the fact that glucose (which provides energy) is diverted to muscles and away from the brain and the hippocampus (which encodes memories).  In fact, the hippocampus may have some degradation due to chronic stress and the diversion of resources, like glucose. On the other hand, stress mediated by norepinephrine/noradrenaline can act through the amygdala, which I explained before, with direct projections to the hippocampus to enhance specific memory encoding.  This comes into play with flashbulb memories (such as where you were when you heard about an event- like when JFK was shot or 9/11) and also in post-traumatic stress disorder (PTSD) when a person may re-experience a stressful event or be “haunted” by the memories of it. [Image Source]

    Stress and Memory

    Cortisol is another hormone released by the adrenal glands during stress.  Cortisol is more of a long-term stress hormone, as it is not immediately released during stress (like epinephrine/adrenaline), but if the stress is severe enough or long-lasting, it will be.  Cortisol seems to prevent encoding of new memories as well as memory retrieval.  In every day life, this can have big effects on exams for college students… the more stressed they are, the more difficult it will be to form and retrieve the information they have studied.  In other situations, this might be a good thing. 

    It is thought that this might also be driven by the fact that glucose (which provides energy) is diverted to muscles and away from the brain and the hippocampus (which encodes memories).  In fact, the hippocampus may have some degradation due to chronic stress and the diversion of resources, like glucose.

    On the other hand, stress mediated by norepinephrine/noradrenaline can act through the amygdala, which I explained before, with direct projections to the hippocampus to enhance specific memory encoding.  This comes into play with flashbulb memories (such as where you were when you heard about an event- like when JFK was shot or 9/11) and also in post-traumatic stress disorder (PTSD) when a person may re-experience a stressful event or be “haunted” by the memories of it.

    [Image Source]

     

  2. 10:17 26th Jan 2012

    Notes: 64

    I had a great question from floating-point that I started to answer earlier this week.  Let’s get back to ApoE e4.  Depending on the number of alleles (you can have up to two, one from each parent), there is an increasing risk of developing Alzheimer’s. People with no ApoE e4 alleles have a 9% risk of getting Alzheimer’s.  Compare that to a 27% risk with one ApoE e4 allele and 55% risk with two ApoE e4 alleles.  Overall, this mutation accounts for about 40% of all Alzheimer’s cases.  The only other genes that are related to Alzheimer’s are causal, which means if you have that mutation, you WILL get Alzheimer’s, but they only account for about .5% of all Alzheimer’s cases.  A few of these genes are AP1 and Presenilin 1 and 2, for example.  The interesting thing is that most of these genes affect APP (Amyloid-Beta Precursor Protein), which is cleaved (cut into a smaller piece) to become amyloid-beta.  It is important to note that amyloid-beta is a normal protein and even with normal aging, there are some amyloid-beta plaques that form.  This makes it extra complicated.  It seems that it might have to do with how amyloid-beta is cleaved (the lengths of the protein once it has been cut normally) and how well it is broken down that might lead to this normal process becoming Alzheimer’s.  There is some evidence that ApoE might help breakdown amyloid-beta and that the e4 allele might not do it as efficiently as the other variants of ApoE, which leads to pathological build up and widespread amyloid-beta plaques.  It isn’t entirely clear at this point, however. I’ve also added a picture to help show the Alzheimer’s brain and degeneration that occurs in the disease progression (above).  It’s pretty marked post-mortem (after death), as you can see. [Image Source]

    I had a great question from floating-point that I started to answer earlier this week.  Let’s get back to ApoE e4.  Depending on the number of alleles (you can have up to two, one from each parent), there is an increasing risk of developing Alzheimer’s.

    People with no ApoE e4 alleles have a 9% risk of getting Alzheimer’s.  Compare that to a 27% risk with one ApoE e4 allele and 55% risk with two ApoE e4 alleles.  Overall, this mutation accounts for about 40% of all Alzheimer’s cases.  The only other genes that are related to Alzheimer’s are causal, which means if you have that mutation, you WILL get Alzheimer’s, but they only account for about .5% of all Alzheimer’s cases.  A few of these genes are AP1 and Presenilin 1 and 2, for example.  The interesting thing is that most of these genes affect APP (Amyloid-Beta Precursor Protein), which is cleaved (cut into a smaller piece) to become amyloid-beta. 

    It is important to note that amyloid-beta is a normal protein and even with normal aging, there are some amyloid-beta plaques that form.  This makes it extra complicated.  It seems that it might have to do with how amyloid-beta is cleaved (the lengths of the protein once it has been cut normally) and how well it is broken down that might lead to this normal process becoming Alzheimer’s.  There is some evidence that ApoE might help breakdown amyloid-beta and that the e4 allele might not do it as efficiently as the other variants of ApoE, which leads to pathological build up and widespread amyloid-beta plaques.  It isn’t entirely clear at this point, however.

    I’ve also added a picture to help show the Alzheimer’s brain and degeneration that occurs in the disease progression (above).  It’s pretty marked post-mortem (after death), as you can see.

    [Image Source]

     

  3. 17:57 23rd Jan 2012

    Notes: 16

    floating-point asked: What's your opinion on the origins of Alzheimer's disease (tau vs. beta amyloid as causative)? Also, it seems that cholesterol plays a role in the disease based on epidemiological and genetic association studies (APOE e4 mutations). What's your view on the biochemical basis for this? Perhaps an impact on APP processing at the membrane level?

    These are really fantastic questions!  I do not have a ton of insight into the field as it really doesn’t align with my research.  This makes me much less partial than others perhaps.  I do find it very interesting, so I have read up on it though.

    For those who don’t know, Alzheimer’s can only be truly diagnosed post mortem, when you can see neurofibrillary tangles (tau) build up inside neurons and beta amyloid plaques outside the cells, both seeming to contribute to the widespread neurodegeneration (brain matter deterioration) that causes the observed changes in patients with Alzheimer’s.

    There are people in either camp of the “which comes first/ which affects Alzheimer’s brains the most” as far as tau or amyloid beta goes.  There was a paper back in 2008 (I believe- maybe early 2009) where they attempted to vaccinate against amyloid beta in people with very early stage Alzheimer’s and found that it did prevent amyloid beta build up in some patients, but did not slow or prevent the progression of Alzheimer’s.  It had been highly successful in mouse models of Alzheimer’s and was very disappointing.  It lent a lot of hope to the people in the tau camp, but it doesn’t mean that amyloid beta would not be causing Alzheimer’s.  There may have been something caused by the vaccine that led to plaques being toxic when broken down or it could be that since they only administered to patients who already had some symptoms that it was too late… it isn’t clear.

    The APOE e4 mutations is also interesting.  As is your question on how it seems to impact APP.  I am going to save these for another post so that this one doesn’t become too dense/long.  Look for it later this week!!

    Thanks again for the great questions!!

     

  4. 09:42 18th Jan 2012

    Notes: 46

    Since my last post about stress, I’ve gotten a lot of questions about what all stress does to the brain.  Stress has a lot of big, widespread effects on both the nervous system and the body. Stress increases production of the hormones epinephrine (aka adrenaline) and norepinephrine (aka noradrenaline) and enhances activity of the sympathetic nervous system.  The sympathetic nervous system is responsible for “fight or flight” responses systemically and increases heart rate, dilates the lungs (so you can get more oxygen), increases blood pressure, etc.  All of the things your body would need to do to be able to run away quickly or put up a good fight.  It also decreases activity in parts of the body that aren’t as necessary to conserve energy- for instance, it decreases metabolism and the immune system.  When all of these things happen short term, it’s actually good- you can put all your energy towards solving the problem that is making you stressed and respond to emergency situations better.  Long-term stress means you will put on more weight (due to decreased metabolism), be more prone to illness (due to suppressed immune system), have high blood pressure, etc.  This isn’t to say you want to prevent stress- it’s all about managing stress so that your body can use it appropriately. [Image Source]

    Since my last post about stress, I’ve gotten a lot of questions about what all stress does to the brain.  Stress has a lot of big, widespread effects on both the nervous system and the body.

    Stress increases production of the hormones epinephrine (aka adrenaline) and norepinephrine (aka noradrenaline) and enhances activity of the sympathetic nervous system.  The sympathetic nervous system is responsible for “fight or flight” responses systemically and increases heart rate, dilates the lungs (so you can get more oxygen), increases blood pressure, etc.  All of the things your body would need to do to be able to run away quickly or put up a good fight.  It also decreases activity in parts of the body that aren’t as necessary to conserve energy- for instance, it decreases metabolism and the immune system. 

    When all of these things happen short term, it’s actually good- you can put all your energy towards solving the problem that is making you stressed and respond to emergency situations better.  Long-term stress means you will put on more weight (due to decreased metabolism), be more prone to illness (due to suppressed immune system), have high blood pressure, etc.  This isn’t to say you want to prevent stress- it’s all about managing stress so that your body can use it appropriately.

    [Image Source]

     

  5. 15:30 20th Dec 2011

    Notes: 169

    Let’s talk a little about stress in the brain.  Most students have recently finished exams for the fall semester, and the holidays bring a whole new set of stressors as people deal with travel arrangements (and even family). One way that stress manifests is by the systemic release of norepinephrine (also called noradrenaline).  In the brain, norepinephrine has widespread effects.  There are three main types of receptors for norepinephrine- alpha 2, alpha 1, and beta receptors.  I list them in this order because alpha 2 receptors require the least amount of norepinephrine to be active, alpha 1 require more, and beta require the most.  This means that alpha 2 receptors are most active in times without stress (when there are low levels of norepinephrine), while alpha 1 and beta are more active during stress. Amygdala, the part of the brain that is very emotionally responsive and can provide “fight or flight” kind of reasoning, is mainly activated by activation of alpha 1 and beta receptors.  On the other hand, prefrontal cortex, which provides a lot of mental control and decision making, is mainly controlled by alpha 2 receptors and is deactivated by alpha 1 and beta receptors.  This means that during stress, prefrontal cortex will be less active and amygdala, which is more primitive and emotionally-driven, will take over. [Picture Source]

    Let’s talk a little about stress in the brain.  Most students have recently finished exams for the fall semester, and the holidays bring a whole new set of stressors as people deal with travel arrangements (and even family).

    One way that stress manifests is by the systemic release of norepinephrine (also called noradrenaline).  In the brain, norepinephrine has widespread effects.  There are three main types of receptors for norepinephrine- alpha 2, alpha 1, and beta receptors.  I list them in this order because alpha 2 receptors require the least amount of norepinephrine to be active, alpha 1 require more, and beta require the most.  This means that alpha 2 receptors are most active in times without stress (when there are low levels of norepinephrine), while alpha 1 and beta are more active during stress.

    Amygdala, the part of the brain that is very emotionally responsive and can provide “fight or flight” kind of reasoning, is mainly activated by activation of alpha 1 and beta receptors.  On the other hand, prefrontal cortex, which provides a lot of mental control and decision making, is mainly controlled by alpha 2 receptors and is deactivated by alpha 1 and beta receptors.  This means that during stress, prefrontal cortex will be less active and amygdala, which is more primitive and emotionally-driven, will take over.

    [Picture Source]

     

  6. 12:22 2nd Dec 2011

    Notes: 9

    miklo-west310 asked: can you tell me some things about an a sciatic nerve ?

    The sciatic nerve is the collection of neurons coming out of the base of the spine and innervating all along the lower back, legs, and feet.  Sciatica is where the nerve is being pressed upon (usually by a bulging disc in the spinal cord) and so the nerve causes the person to feel pain, tingling, and/or weakness down the course of the leg (basically to everything it innervates).  I am not sure exactly what sort of things you wanted to know, but I hope this helps!

     

  7. 12:51 12th Nov 2011

    Notes: 75

    I was recently thinking about inhibition in the brain, which brought me to think about the multitude of different types of inhibitory neurons. The one pictured above is a Chandelier Cell. I think you can guess why it is called such (since it looks like a chandelier). I think it’s one of the prettiest inhibitory neurons in the brain, but that is of course, my opinion. Inhibitory neurons work most often by releasing the neurotransmitter GABA onto another neuron. GABA often opens chloride (Cl-) channels that hyperpolarize the neuron. When the membrane is hyperpolarized, it is much less likely to fire an action potential and send its signal on to the next neuron. Inhibition can essentially prohibit the signal transfer. (Note: This explanation is simplified, but that is the general idea.) Different inhibitory neurons can do this in different ways. Chandelier cells have those ends that look kind of like candles. Those are often wrapped around the axons of other neurons. By applying GABA on the axon of another neuron, the chandelier cell has a much better chance of stopping the action potential (than if they were connecting to the other neuron’s dendrites for example). What is also interesting is that chandelier cells are much more prevalent early in life, as they are a more primitive form of inhibition. As the brain develops, it uses less chandelier cells and more basket cells and other inhibitory neurons that are more sophisticated in their actions. Incorrect functioning of these may be implicated in schizophrenia and autism, among other disorders. [Click through image for source]

    I was recently thinking about inhibition in the brain, which brought me to think about the multitude of different types of inhibitory neurons. The one pictured above is a Chandelier Cell. I think you can guess why it is called such (since it looks like a chandelier). I think it’s one of the prettiest inhibitory neurons in the brain, but that is of course, my opinion.

    Inhibitory neurons work most often by releasing the neurotransmitter GABA onto another neuron. GABA often opens chloride (Cl-) channels that hyperpolarize the neuron. When the membrane is hyperpolarized, it is much less likely to fire an action potential and send its signal on to the next neuron. Inhibition can essentially prohibit the signal transfer. (Note: This explanation is simplified, but that is the general idea.)

    Different inhibitory neurons can do this in different ways. Chandelier cells have those ends that look kind of like candles. Those are often wrapped around the axons of other neurons. By applying GABA on the axon of another neuron, the chandelier cell has a much better chance of stopping the action potential (than if they were connecting to the other neuron’s dendrites for example). What is also interesting is that chandelier cells are much more prevalent early in life, as they are a more primitive form of inhibition. As the brain develops, it uses less chandelier cells and more basket cells and other inhibitory neurons that are more sophisticated in their actions. Incorrect functioning of these may be implicated in schizophrenia and autism, among other disorders.

    [Click through image for source]

     

  8. 13:12 27th Oct 2011

    Notes: 133

    image: Download

    Have you ever wondered why people say when you see a bear you should stand still?  Just from a logical standpoint, it sounds pretty stupid to stay still when something might attack you.  However, when you learn a bit more about the visual system, it might not be such bad advice. We process visual information in two pathways: the ventral and dorsal streams.  The ventral stream processes color and form- the “what” of an object.  The dorsal stream processes the “where”- movement and depth (how far away) of an object.  We take both of these things and their combination into the way we view the world completely for granted. There is evidence that predators (like bears) may not have much of a ventral pathway and rely mostly on the dorsal stream… and this makes sense.  They need to know where the prey is in relation to themselves, so they can get to it and eat it quickly before it can run for cover.  The exact form of the prey is not so significant (you don’t need to know that a particular rabbit’s head is rounder than most rabbits to know that it could make a good next meal).  Therefore, if you stand still, the bear would not be very good at picking you out from the trees and landscape.  That is, until you move, and then it knows that a possible meal could be over that way and it can focus on where you are and if you might make decent prey. [Image Source]

    Have you ever wondered why people say when you see a bear you should stand still?  Just from a logical standpoint, it sounds pretty stupid to stay still when something might attack you.  However, when you learn a bit more about the visual system, it might not be such bad advice.

    We process visual information in two pathways: the ventral and dorsal streams.  The ventral stream processes color and form- the “what” of an object.  The dorsal stream processes the “where”- movement and depth (how far away) of an object.  We take both of these things and their combination into the way we view the world completely for granted.

    There is evidence that predators (like bears) may not have much of a ventral pathway and rely mostly on the dorsal stream… and this makes sense.  They need to know where the prey is in relation to themselves, so they can get to it and eat it quickly before it can run for cover.  The exact form of the prey is not so significant (you don’t need to know that a particular rabbit’s head is rounder than most rabbits to know that it could make a good next meal).  Therefore, if you stand still, the bear would not be very good at picking you out from the trees and landscape.  That is, until you move, and then it knows that a possible meal could be over that way and it can focus on where you are and if you might make decent prey.

    [Image Source]

     

  9. 12:05 25th Oct 2011

    Notes: 10

    pooleeanderson asked: Hey, I'm new to reading your blog, and I haven't gotten to all the posts, but I was wondering what opinions you had on the theory of neuroplasticity? I know many neurologists have long thought in terms of localizationism. I find neuroplasticity to be a very compelling topic and certainly something that could open entirely new doors in the study of the brain. By the way, your blog is awesome and very informative. Thanks!

    This is an interesting debate.  Neuroplasticity says that the brain can change with use, while localizationists believe that the brain has fixed uses, such as one place for representation of a leg or finger, etc.

    I am sure a lot of people would have their own opinions about this, but I do completely believe in neuroplasticity.  Well, to an extent- I am not going to say that the brain is constantly changing or that everything can change, but some of it at least does.  At this point in time, there is a great deal of evidence that the brain is plastic (which just means that it can change with time/use).  For instance, we know that people who play the violin, which requires a lot of finger dexterity, have much larger representations of the left fingers than people who do not play a stringed instrument.  It is also generally acknowledged now that there are “critical periods” during which parts of the brain are plastic and can easily be changed.  For instance, braille can be difficult to learn later in life, but it is much more easily learned when a person is young.  If it is learned during this young age (during the critical period), there will be different representations of somatosensory (touch) stimuli in the brain to pick out small differences in the raised bumps of braille.  In fact, there is also evidence that visual cortex in the blind can be recruited for somatosensation (touch) to allow them to better read braille and other things, if they learn at a young enough age (thought to be before 16 years old) so as to be done during a critical period for this change.  This use of visual cortex for tactile discrimination will not happen in adults, but there will be smaller neuroplastic changes, such as within somatosensory cortex.

    Anyway, those are my relatively quick thoughts about neuroplasticity.  I am sure general scientific opinion will begin to change with time as more evidence and knowledge accumulates.  (I mean, hey, we’ve totally moved away from phrenology, which was thought to be pretty accurate by a decent number of people a couple centuries ago).

     

  10. 11:41

    Notes: 6

    erikaajacksonn asked: I have had Chronic Inflammatory Demyelinating Polyneuropthy (CIDP) for four years now. It is an aquired inflammatory disorder of the peripheal nervous system. Suddenly I strained to move my arms, shortly after my legs followed. I receive IViGs about every month and when I asked my doctor how they help me, he couldn't really answer. I was just curious if you could shed some light on the process for me, I would appreciate it :)

    I am very sorry to hear that you have CIDP.  That must be incredibly difficult… CIDP, as a simple and quick explanation for people who do not know, is where the immune system essentially over-reacts and attacks myelin on neurons.  As this person has noted, it definitely affects motor neurons, which rely on myelination for correct and rapid action.  Myelin is an insulator of axons that carry information (action potentials) to the next neuron, making the communication faster and possible across long distances (such as from the brain to your feet).  When neurons become demyelinated, they are often unable to work properly and so, in the case of motor neurons, they are unable to make your muscles move.

    IVIG is Intravenous Immunoglobulin, which is a therapy that can be used for many autoimmune disorders.  It is just antibodies (antibodies are proteins used to recognize “bad” things like viruses and bacteria so that the body can identify and remove them) distilled from donated blood used as a treatment.  It seems that the exact mechanism is still under debate, which may have been what your doctor was alluding to.  Essentially, at the end of the day, IVIG suppresses inflammation and prevents its over-activity.  There are pieces of how it works that have been identified, but the exact mechanism isn’t clear.  For instance, it may simply be that the addition of more antibodies causes the body to recognize that there are too many and remove those as well as some of the ones that the body had been over-using to attack the myelin.  It may also be that some of the IVIG antibodies recognize the abnormal antibodies that you have and prompt their removal.  It may even be something else entirely… for instance, there is evidence of some sort of immune complex forming or action on T-cells.

    I do hope that this therapy is helping you (the really important result), and I am sorry that I cannot provide more information.  Hopefully what little I do know is helpful in some way!

     

  11. 14:11 22nd Feb 2011

    Notes: 60

    If you haven’t done this before, try it.  It’s about selective attention and is always pretty crazy.  I’ll talk more about this process and why it matters later.

     

  12. 14:05 1st Feb 2011

    Notes: 28

    rTMS ( repetitive Transcranial Magnetic Stimulation) Another technique that can be used to treat Parkinson’s, Tourette’s, OCD, and some other disorders, is rTMS.  rTMS uses essentially an electromagnetic pulse to disrupt the electric activity (action potentials) of neurons.  rTMS can be focused on a specific region of the brain (just like the DBS I talked about before), so we can target and inactivate regions that will help increase movements in Parkinson’s patients.  The weakness of rTMS is that is temporary, so you have to do it fairly often to have longterm benefits.  It also takes a bit of time each time it is done and can be fairly expensive. The image above is from just regular TMS, which is usually a single, targeted pulse.  This can actually be used to enhance activity in a specific region. [Image Source]

    rTMS ( repetitive Transcranial Magnetic Stimulation)

    Another technique that can be used to treat Parkinson’s, Tourette’s, OCD, and some other disorders, is rTMS.  rTMS uses essentially an electromagnetic pulse to disrupt the electric activity (action potentials) of neurons.  rTMS can be focused on a specific region of the brain (just like the DBS I talked about before), so we can target and inactivate regions that will help increase movements in Parkinson’s patients.  The weakness of rTMS is that is temporary, so you have to do it fairly often to have longterm benefits.  It also takes a bit of time each time it is done and can be fairly expensive.

    The image above is from just regular TMS, which is usually a single, targeted pulse.  This can actually be used to enhance activity in a specific region.

    [Image Source]

     

  13. 10:41 24th Jan 2011

    Notes: 19

    daath asked: Can you tell me about the frontal lobes, what they effect, and how they grow? And/or, when/how they became a major player in the Homo Sapien?

    First of all, thanks very much for the question- evolutionary biology/neuroscience is very interesting.  The frontal lobe is devoted to higher cognitive reasoning, so that includes decision making, goal-directed behavior, working memory (holding a thought in your head), and emotions.  As for how they grow, I assume you mean evolutionarily.  We’re not really sure how exactly they evolved (like so many other things), but we know that the size of the frontal lobe is up to 6x bigger in humans than it is in lesser monkeys or human ancestors.  (Interestingly, there was a study that showed that the frontal lobes might be just as big in some monkeys, such as the great apes.) Take that in comparison to the brain being only about 3x bigger (in comparison to body size).

    A lot of what “makes us human” is located and controlled in the frontal lobe.  Homo sapiens were really the first organisms with such a large frontal lobe, and it is one of the defining points of our species.  However, it seems like the most important part (of the brain) in causing us to “be human” might actually be the folds in the brain.

    Our brains, even compared to other primates, have an extreme number of folds.  This means that we can fit a lot more neurons in less space.  The outermost layers of the brain are the cell bodies, so the more folds we have on the surface, the more neurons we have.  However, we know that is not just the number of neurons/folds alone that make us intelligent.  There was a project that genetically knocked out a gene that causes normal neuron death early in development.  This created mice with many folds in the brain and many neurons that wouldn’t normally be there.  Unfortunately, they were not “genius” mice- they were hardly viable (they did not live for long if at all).  I can talk later about the “doogie” mice that did have seemingly superior intelligence compared to regular mice- and it was due to a different gene unrelated to brain folding.  In other words, it seems like a lot of different factors add up to create Homo sapiens and define us a species.  Large frontal lobes, many neurons, and a bunch of different genes effecting molecular systems developed over time to make us into what we are.

     

  14. 09:33 21st Jan 2011

    Notes: 84

    Another treatment for Parkinson’s: DBS Deep brain stimulation (DBS) involves the implanting of electrodes in the brain that effectively “inactivate” a certain region.  It can be quite sophisticated, using multiple electrodes that can then have different patterns of stimulation.  There is a pacemaker that is implanted elsewhere in the body, usually where it can be removed to replace batteries and the like without too bad of side effects (so not in the brain tissue).  In Parkinson’s, the electrodes are surgically implanted into the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi).  For a refresher on the basal ganglia pathways, go here. STN excites GPi and GPi inhibits thalamus, both of which effectively decrease movements.  In Parkinson’s, patients are having trouble moving due to the decreased dopamine feeding into the basal ganglia loops.  Therefore, acting on STN or GPi and effectively inactivating those regions makes it so that movements will be easier. It is also interesting to note that DBS can be used on other disorders, such as severe cases of obsessive-compulsive disorder (OCD) and Tourette’s Syndrome.  Tourette’s is characterised by motor and verbal tics that can be very intrusive, not what you usually see on TV (for instance, I know a patient whose uncontrollable tic is to poke their eye and they had blinded that eye with it).  DBS of the thalamus usually can be helpful for patients suffering from Tourette’s (I think you can figure out why it might be from what you know about the basal ganglia circuitry). There are still more potential treatments for Parkinson’s that I will continue to discuss. [Image Source]

    Another treatment for Parkinson’s: DBS

    Deep brain stimulation (DBS) involves the implanting of electrodes in the brain that effectively “inactivate” a certain region.  It can be quite sophisticated, using multiple electrodes that can then have different patterns of stimulation.  There is a pacemaker that is implanted elsewhere in the body, usually where it can be removed to replace batteries and the like without too bad of side effects (so not in the brain tissue). 

    In Parkinson’s, the electrodes are surgically implanted into the subthalamic nucleus (STN) or the internal segment of the globus pallidus (GPi).  For a refresher on the basal ganglia pathways, go here. STN excites GPi and GPi inhibits thalamus, both of which effectively decrease movements.  In Parkinson’s, patients are having trouble moving due to the decreased dopamine feeding into the basal ganglia loops.  Therefore, acting on STN or GPi and effectively inactivating those regions makes it so that movements will be easier.

    It is also interesting to note that DBS can be used on other disorders, such as severe cases of obsessive-compulsive disorder (OCD) and Tourette’s Syndrome.  Tourette’s is characterised by motor and verbal tics that can be very intrusive, not what you usually see on TV (for instance, I know a patient whose uncontrollable tic is to poke their eye and they had blinded that eye with it).  DBS of the thalamus usually can be helpful for patients suffering from Tourette’s (I think you can figure out why it might be from what you know about the basal ganglia circuitry).

    There are still more potential treatments for Parkinson’s that I will continue to discuss.

    [Image Source]

     

  15. 13:15 20th Jan 2011

    Notes: 42

    Treatment for Parkinson’s : L-DOPA The most obvious treatment for Parkinson’s would be to replace the dopamine in the brain that is being lost by dopaminergic neuron degeneration.  Dopamine itself, however, cannot pass the blood brain barrier to get into the brain.  L-DOPA, the precursor of dopamine (it is broken down to create dopamine), can pass the blood brain barrier however.  This means that we can administer L-DOPA, it will enter the brain, and then dopaminergic neurons with DOPA decarboxylase (the enzyme that breaks down L-DOPA) will convert L-DOPA into dopamine, giving the dopaminergic neurons that remain in the brain more dopamine to release and make up for the ones that have died. This treatment works very well in the early stages of Parkinson’s.  Unfortunately, as time goes on, more and more L-DOPA is needed to help movement because more neurons are dying in the substantia nigra and there is a bit of tolerance to L-DOPA.  At the higher doses that are needed, there are much more dramatic side effects, including horrible hallucinations, twitches, obtrusive mood swings, etc.  Knowing what we know about the basal ganglia circuitry, we know that these are due to increased DA activating the direct pathway of the basal ganglia and increasing thoughts/emotions as well as movements. Unfortunately, because of these side effects, L-DOPA is just a temporary treatment and cannot be used as long-term as needed for someone trying to live with Parkinson’s disease.  There are other possible treatments that I will discuss next. [Image Source]

    Treatment for Parkinson’s : L-DOPA

    The most obvious treatment for Parkinson’s would be to replace the dopamine in the brain that is being lost by dopaminergic neuron degeneration.  Dopamine itself, however, cannot pass the blood brain barrier to get into the brain.  L-DOPA, the precursor of dopamine (it is broken down to create dopamine), can pass the blood brain barrier however.  This means that we can administer L-DOPA, it will enter the brain, and then dopaminergic neurons with DOPA decarboxylase (the enzyme that breaks down L-DOPA) will convert L-DOPA into dopamine, giving the dopaminergic neurons that remain in the brain more dopamine to release and make up for the ones that have died.

    This treatment works very well in the early stages of Parkinson’s.  Unfortunately, as time goes on, more and more L-DOPA is needed to help movement because more neurons are dying in the substantia nigra and there is a bit of tolerance to L-DOPA.  At the higher doses that are needed, there are much more dramatic side effects, including horrible hallucinations, twitches, obtrusive mood swings, etc.  Knowing what we know about the basal ganglia circuitry, we know that these are due to increased DA activating the direct pathway of the basal ganglia and increasing thoughts/emotions as well as movements.

    Unfortunately, because of these side effects, L-DOPA is just a temporary treatment and cannot be used as long-term as needed for someone trying to live with Parkinson’s disease.  There are other possible treatments that I will discuss next.

    [Image Source]