Glossary for Brimblecombe et al (2023)
α-synuclein: pronounced alpha-synuclein, is a substance made by lots of different brain cells. We still don’t really know what α-synuclein’s normal job in a cell is, but we know that it is found in the cell’s machinery that releases chemicals including dopamine. Sometimes α-synuclein is on its own, sometimes in small groups of α-synuclein and other times in big lumps of α-synuclein. We think the job of α-synuclein is different when it is on its own or with other bits α-synuclein. We know that people who have too much or the wrong type of α-synuclein are very likely to get Parkinson’s. We still don’t fully understand why α-synuclein goes from helping dopamine cells to harming them in people with Parkinson’s, but we know that α-synuclein can make the dopamine cells need lots of energy. When the dopamine cells use lots of energy, they try to make extra fuel and then make toxins, like a broken boiler chucking out smoke. We think that when the dopamine cells run out of energy or make too many toxins they die.
Average: We take lots of measurements of the same thing because the more you measure something the closer you get to the “real” number. Because we use animal tissue we have to be careful choosing how many times to take the same measurement, it’s important we get close to the right number, but it would be unethical using more animals than we need. Before we start any experiments we use our past experience to say how many animals we are likely to need to see a “statistically significant” difference. If an experiment needs to use too many animals we re-design our experiments to ask a better question.
Calb1: is short-hand for Calbindin-D28K (you can see why we abbreviate!). Calb1 acts like a calcium sponge, mopping up extra calcium once a message has been sent. We know that calb1 can also deliver calcium to where it is needed and also stop it from spreading too far.
Calcium: When you think of “calcium” perhaps you think of healthy teeth and bones, or perhaps you think of the shiny lump of metal fizzing across water from that chemistry lesson many years ago! When we are talking about calcium, we actually mean a calcium ion (often written Ca2+). This is the “reactive” form of calcium that exists in our cells. Calcium (Ca2+) in this form easily dissolves in water, so can travel throughout the cell and is very keen to stick parts of the cell machinery and kick them into action. When it’s waiting to be released, dopamine is stored in little bags near the outside of the cell. When the bags are ready to be released the bags are “docked” into a big machine called “the snare complex”, which acts like a trebuchet, flinging the bags of dopamine out of the cell! Calcium binds to the trigger mechanism of the trebuchet, allowing the dopamine to leave the cell and send a message to its neighbours.
Cocaine: is a drug that stops the dopamine transporter from working. When cocaine is present, the dopamine message is much bigger and longer lasting.
Control conditions: when we are making comparisons we call the normal or baseline “control conditions”. I,e, it is the starting point for all of our comparisons.
Dopamine-2-Receptor (D2R): A receptor is a special lock on the outside of the cells. They can only be unlocked by their own special chemical messenger key. The D2-receptor is unlocked by dopamine and it makes the cell less likely to send on another message, we call this “inhibitory”. D2-receptors are on lots of different cell types, but are also on dopamine cells themselves, D2-receptors stop the cell from sending the same message more than once, or the message being too loud. We call this an auto-receptor. See Receptor for more general information.
Decision tree: is a sorting algorithm a computer does to sort data into categories and heirachies. Here is a really good video to explain in more detail if you are interested https://www.youtube.com/watch?v=_L39rN6gz7Y.
Dopamine: is a chemical made and released by some brain cells. It signals to other brain cells by fitting like a key into special locks on cells called “receptors”. There are two types of receptors, one type makes cells more active and the other make them less active. We are still working hard to fully understand what dopamine’s job is in the brain, but we think it is important for choosing which actions our body should be doing and stopping the actions that we shouldn’t. When someone gets Parkinson’s, there isn’t enough dopamine in the brain, making it hard to choose the right action (like walking) and stop other actions (like tremors). Dopamine is also very important for deciding if an action is helpful (makes us feel good) or unhelpful (makes us feel bad). Unfortunately sometimes dopamine signals something feels good even when it’s not good for us, which is why so many drugs of abuse work on the dopamine system. Scientists will often shorten dopamine to “DA”
Dopamine transporter: is a carrier that moves dopamine from the outside of dopamine cells back inside, so the dopamine is ready to be released again. The dopamine transporter is linked to the machine that releases dopamine so it can stop too much dopamine from being released. The dopamine transporter sits in the “cell membrane”, if you change the make-up of the cell membrane you can change how well the dopamine transporter works (think of how well you worked at school depended on where in the classroom you were and who you were sitting next to!). It takes energy to make the dopamine transporter work so balancing the amount of dopamine released and how long it should stay around for is important. The dopamine transporter is often written as “DAT”.
Error: Whenever we make a measurement, it will always be either a bit bigger or smaller than the true value. To get as close to the true answer we measure things lots of times. The error is how much uncertainty we have about the accuracy of our measurement.
Exponential decay curve: Is a graph that shows what happens when the amount of something halves after a set amount of time known as its “half-life”. i.e. imagine you have a basket of apples with a half-life of 1 second: if you start with 12 apples, one second later you will have 6 apples, after 2 seconds you will have 3 apples and so on. These graphs are the opposite of the “exponential growth curves” you will have seen so much about during the peak of the covid-19 pandemic.
Fast-scan cyclic voltammetry is a technique that lets us measure how much dopamine is outside a cell. It works very quickly so we can get lots of measurements in a single second that we can play back like a movie to see how much dopamine there is and how long it stays around for. We can make the dopamine come out of the cells by using an electric pulse. We can use fast-scan cyclic voltammetry in brain slices or in awake moving animals. Some scientists have even used fast-scan cyclic voltammetry in people when they have brain surgery! Fast-scan cyclic voltammetry is often written as FCV
GBA: is the gene that encodes for an enzyme called Glucocerebrosidase. We shorten Glucocerebrosidase to GCase. When you have only one copy of GBA gene you make about half the normal amount of GCase. GCase is one of the machines that chops up old bits of cells, its very important for keeping cells healthy. People with Gaucher’s disease have only one copy of the GBA gene.
Isradipine: is a drug used by people with heart conditions and recently went through a phase3 trial for Parkinson’s. Initially it was found to not help PwP but reanalysis may show some small improvement, but unfortunately it isn’t the silver bullet we were hoping for.
L-type Calcium channel: is a special gate that lets calcium into cells. The L-type calcium channel only opens when cells are ready to send a message. We call this “voltage-gated”.
OPDC: is the “Oxford Parkinson’s disease centre” it was funded by two Parkinson’s UK monument grants and links lots of different types of scientists together so we can best ask questions that will tell us more about why people get Parkinson’s and hopefully how we can help them.
Receptor: A receptor is a special lock on the outside of the cells. They can only be unlocked by their own special chemical messenger key. When the chemical messenger unlocks the receptor, it passes on the message to its cell. The messages that receptors pass on can get quite complicated. Therefore we try to fit them into two categories: excitatory and inhibitory. Excitatory messages make the cell more likely to pass on the message to the next cell and inhibitory messages make them less likely. A cell must balance lots of different excitatory and inhibitory messages to choose whether to talk to the next cell.
Striatum: The striatum is part of the brain. It is the part of the brain where most of the dopamine is released. We can roughly divide the striatum into two parts into the “dorsal” I,e, top and “ventral” i.e. bottom. The “dorsal”/top part is vulnerable in Parkinson’s and the “ventral”/bottom part is fairly resistant in Parkinson’s.
Statistically significant: often on the pictures that scientists make of their measurements you will see little stars/asterisk (*). These are usually there to show a difference between groups are “statistically significant”. What this means is that the difference that we see between the groups is unlikely to be due to chance. We work out statistical significance by taking lots of measurements of the same thing and see how different those measurements are from each other, this is called the “error”. We do this for two or more different groups and then see if the “errors” overlap. If the errors don’t overlap we often say the difference is statistically significant. Just because a difference is “statistically significant” doesn’t mean that it matters in real life, scientists must do lots of different comparisons to work out which differences are important. Often one scientist will find that there seems to be an important difference, but other scientists won’t see the same difference. They may not see the same difference either because the difference was due to chance, or because you can only see the difference when an experiment is done in a certain way. Usually, important differences are the ones seen by lots of different experiments done by lots of different scientists.
Wild-type: is a name given to a type of mouse that we consider “normal”. These mice are not very similar to truly wild mice though. They have been bred in labs to be as similar as possible to each other.