Threlfell et al 2021 Glossary
ABCA1 transporter: Is a carrier that moves cholesterol from inside a cell to outside. It uses energy to move the cholesterol. It can be stopped from working with a drug called “Probucol”.
α-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 is found in the cell’s machine 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 changes when it’s 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 hurting 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 it tries to make extra fuel that makes 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 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.
Cholesterol: is a type of lipid (fat). It changes how wide and wobbly a cell membrane is. Cholesterol also makes sure parts of a cell machinery stay where they’re needed.
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”.
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
Immunohistochemistry: is a technique in molecular biology that is used a lot. It uses special tags called antibodies that only stick to the thing you are interested in. The antibodies have their own coloured tags so we can see and count the things we are interested in down a microscope.
Membranes: Is the skin that goes around the cell. It is an important barrier that lets cells talk to each other.
Michaelis-Menten plot: is a special type of graph that can tell us about how well cell machines work and how many cell machines there are. Michaelis-Menten plots work for machines that changes the amount of something (either by making it, breaking it or moving it) by recording how the amount of “the thing” changes over time compared to how much of “the thing” there was to start with. The computer works out two numbers that tell us about the machine: Vmax, is the fastest the machines are able to work, Vmax number goes up when there are more machines; and Km which is how much of “the thing” you need to start with for the machine to work half of its maximum speed, Km is a small number when the machine is very efficient. For anyone interested in learning more here is a nice overview of Michaelis-Menten plots of YouTube: https://www.youtube.com/watch?v=rCVRC-AQ54M
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.
Proximal-ligation assay: is quite a new technique in molecular biology. It can tell if two things you are interested in can be very close together, close enough to control each-other. It works by putting half of a code on each partner and when they are close enough together the code is complete, and you get a signal (like an old-school broken-heart friendship pendant!)
Radio-ligand binding: is a technique in molecular biology, similar to immunohistochemistry it is used to count the number of “things” you are interested in. It works for parts of the cell that have a very specific partner. We make the partner radioactive, and then we can count how much of the partner we see sticking to cells. Radio-ligand binding is good for counting the “working” thing you are interested because you are counting when they are pairing with their special partner.
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.
Statistically significant: often on the pictures 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.
Return to "A story about how α-synuclein changes the comings and goings of dopamine".