Interview with Microglia Expert Prof. Beth Stevens

Beth Stevens received her PhD in Neuroscience in 2003 from the University of Maryland, College Park and completed her postdoctoral fellowship at the Stanford University School of Medicine in 2008. She is a recipient of several awards including the Smith Family Award for Excellence in Biomedical Research, Dana Foundation Award (Brain and Immunoimaging), Ellison Medical Foundation New Scholar in Aging award, John Merck Scholar Program, and MacArthur Fellows Program.

Dr. Stevens’s current studies are aimed to define cellular and molecular mechanisms underlying complement dependent and independent synapse elimination during development and disease. Current research questions include: How are CNS synapses selectively targeted for elimination? Is complement-dependent synapse elimination an activity-dependent process? What is the role of astrocytes and microglia in synapse development and elimination? The Stevens lab is using a combination of live imaging, molecular, biochemical, and neuroanatomical approaches to address these and other mechanistic questions.

Click here for an introduction to microglia from the team at Neuro Transmissions

The following has been paraphrased from an interview with Prof. Beth Stevens on June 7th, 2018

(Click above to listen to the full audio version or click here for a downloadable version)


What do you think it feels like to be microglia?

I would say very lucky, in that unlike other cells in the brain, microglia can transform their state. They can be beneficial and promote healthy brain activity, or detrimental and facilitate disease. It is a pretty dynamic cell, and can be pretty cool to look at under a microscope because no other cell moves the way they do.

From a recent paper by David Sulzer et al., “Activated microglia have been reported in the substantia nigra of patients with Parkinson’s disease for nearly a century”. Why has it taken so long for the field to really start studying them?

That is the same question that those of us who study these cells ask ourselves in scientific meetings. One of the oldest and most well described hallmarks of neurodegenerative diseases is something called reactive gliosis, a state when microglia and astrocytes transform into ‘activated’ looking cells, it is very striking. Though most people will agree that these cells are important and contribute to disease, it is not clear how they do so.

The challenge in studying them is that we haven’t had good tools or markers to distinguish the different types of microglia. Now we do and that allows us to deeply characterize microglia and their function. We hope that this is going to give us new markers that tell us more about their function in the brain and give us new therapeutic strategies to intervene when they are causing damage.

How many different types of microglia are there?

Right now, we don’t have an answer to that. What we know is that microglia come from the same place during our development and get into our brains very early on. Lately, we have seen that these cells undergo state changes that are distinct based on their environment and stage of development. We just did a large a profile study in the mouse brain looking at microglia from early development to later in life and saw a huge amount of diversity. These different state changes are starting to give us insights into how they respond to their environment and how many different types there are.

How complex is the decision making process that they go through?

It is pretty complex, but it also makes sense if you think about how their counterparts, the macrophages in the peripheral immune system, recognize cells. They are both capable of eating bacteria or smaller cells and particles, and they interact with their environment by reading molecular cues on other cells to decide whether or not to eat them.

Microglia are incredibly dynamic, constantly moving around in the brain and examining the synapses of neurons for cues that tell them whether or not they should eat it. But it gets much more complex than that because they need to be able to prune the right synapses at the right stage of development. In neurodegenerative diseases, either these signals go awry, or microglia can’t read them properly, which leads to over-pruning. We have been studying these cues in terms of normal development to know how this process works so we can later apply that to disease models.

Is there any evidence that any supplements or diets are particularly good for our microglia?

We don’t have any magic pill or diet that can change microglia in any clear way at the moment. But, we do know inflammatory environments can either directly or indirectly effect the activation of microglia. We are trying to figure out how to keep microglia in a state that is beneficial to the brain. If we can figure out those conditions that promote healthy states, it could lead to therapeutic strategies, but first we have to understand them better.

How much do we know about the connection between the gut and microglia activation?

We really don’t understand it yet. There is some interesting data coming out that shows that the gut microbiome is impacting the brain, but how it influences microglia is still not clear, though there is some evidence that they change when the gut microbiome is manipulated. It’s an exciting area because it is really interdisciplinary, but we don’t have any clear answers yet.

What are some of the biggest challenges to studying neurodegeneration?

One of the challenges that we face is that our models don’t accurately reflect what is happening in humans. I would like the field to come together and think about how the different causal genetic pathways in particular can be better modeled. The good news is that there seems to be common pathways or mechanisms in a variety of diseases. Also, new biomarkers and imaging tools are getting us closer to understanding what goes wrong in the brain. But it will take people coming together from disparate fields to work on common problems to really solve these problems.


Click here to learn more about the work of Prof. Beth Stevens

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