Amy Gleichman

This whole paper is incredibly cool - but this virus work in particular is really exciting!

Flyer for a social for Glial Interactions at SfN. Monday Nov 17, 9PM-close, The Smoking Gun, 555 Market St. Microscopy images of two astrocytes (top, red/blue) and an oligodendrocyte and myelin sheaths (bottom, white/red).

If you’re interested in the roles of glia in stroke and TBI, kick off #SfN2025 with a minisymposium on Saturday afternoon in room 6B!

@droligo.bsky.social and I are also hosting a glia get-together Monday night, sponsored by Avantor and @plasmidsaurus.bsky.social - all glia-inclined are welcome!

ATTN: Two faculty positions are available in my department (neuroscience) at the University of Minnesota. This is a general search with no topic focus. November 20th application deadline.

Apply here: hr.umn.edu/jobs/Find-Job
Assistant Prof job code: 364920
Associate/Full Prof job code: 364921

If you’re interested in glia and you’ll be at SfN in San Diego, please join us!

Just a friendly reminder that we’re hiring for the Department of Neuroscience at The Ohio State University!! 🧠 The start of application review has been moved to this Friday, 10/17, but we’ll continue accepting applications until the position is filled!

neurojobs.sfn.org/job/39081/te...

Thanks Michael!

Thanks, Louise!

You’re not sorry 😂 and thanks! Hope to catch up one of these days

Thanks, Wendy!!

Left, red: a bushy, mostly spherical astrocyte in the mouse cortex Right, green: a more elongated astrocyte in the mouse white matter

And finally, a couple of virally-labeled astrocytes, because they are just so pretty. Red is a cortical astrocyte, green is a white matter astrocyte.

I started my own lab about 6 months ago at Ohio State where we’re continuing to look at ways to manipulate astrocyte biology to improve brain repair. We’re also generating new viral tools along the way, for use in research and hopefully in gene therapies for patients down the line.

Take-home message: astrocytes can respond in nuanced ways even to very similar injuries, and those nuances can be leveraged for interventions. Huge thank you to my postdoc mentor, Tom Carmichael, as well as our amazing collaborators Michael Sofroniew, Riki Kawaguchi, and Elle Rathbun.

Looks like yes! Overexpression of Lamc1 in white matter astrocytes led to a smaller fibrotic scar and axotomized region as well as behavioral improvements. This also changed the immune cells entering the area, with a huge increase in Tregs. Overall, Lamc1 in white matter astrocytes improved repair.

We made a lentivirus to overexpress Lamc1 in astrocytes and injected it in the white matter, and saw an increase in vascular remodeling specifically of those larger-caliber vessels. These are kind of weird vessels to have in white matter, which is more capillary-heavy. Are they a good thing?

So it looks like Lamc1 is an endogenous mechanism by which cortical astrocytes improve repair after stroke, and it’s acting specifically to increase remodeling of arterioles and venules. Can we leverage this to improve repair in white matter stroke, where this mechanism doesn’t usually turn on?

Surprisingly, we saw a pretty specific decrease in remodeling of arterioles and venules, but the capillary bed was unchanged. These vessels were all intact; knocking out Lamc1 didn’t affect blood-brain barrier permeability.

Using a variety of metrics, we identified a pro-angiogenic gene (Lamc1) upregulated in cortical astrocytes near the stroke but not white matter astrocytes. We developed a dual-virus CRISPR system to knock it out in astrocytes in the cortex, and found a decrease in vascular remodeling post-stroke.

Vascular remodeling and angiogenesis after a cortical stroke improve brain repair. We’ve known astrocytes in the cortex can help this process (see great work from @m-r-williamson.bsky.social and Theresa Jones), but it’s less clear what’s going on in white matter.

While a lot of responses were shared between the cortical stroke and white matter stroke astrocytes, there were also some really intriguing differences. Top among those: cortical astrocytes were predicted to increase post-stroke vascular remodeling, while white matter astrocytes were not.

But we didn’t see a correlation when we compared this module to astrocytes in other conditions, like aging or models of Alzheimer’s or Huntington’s disease. This module seems to be generalizable to reactive astrocytes within brain injury and inflammation, but not to all reactive astrocytes.

The genes in this module – also heavily immune-related – show similar changes in other datasets where astrocytes are responding to injury and/or inflammation: spinal cord injury, cortical stab wound, systemic inflammation, other stroke datasets.

There are a lot of similarities between the two: the most reactive astrocytes in both stroke models are heavily involved in immune responses. Using network analysis, we found a module of genes that particularly relates to the level of reactivity, regardless of stroke model.

We defined zones of reactive astrocytes in mouse models both a large vessel cortical stroke and white matter stroke, using a lot of phenotypic and morphologic analyses, then used those zones for a transcriptomic analysis.

Astrocytes in the white matter are pretty different from astrocytes in the gray matter. So we also wanted to include that layer of complexity – do white matter and gray matter astrocytes respond differently to stroke?

We’re interested in both large-vessel strokes as well as small strokes that happen in the white matter tracts of the brain, which are clinically distinct forms of stroke. Small lacunar infarcts in the white matter are one of the underlying pathologies of vascular dementia.

Long story slightly longer: Astrocytes react strongly to any kind of injury, like stroke. We wanted to understand more about the range of reactions – how are astrocytes right next to the stroke responding, and how much do those responses change as you get further away from the injury?

Regionally mapped astrocytic responses to cortical and white matter stroke show differential roles in astrocyte-induced vascular remodeling Stroke is a major cause of disability. Astrocytes respond to stroke in a gradated manner, but details of that response and its consequences for tissue…

Thrilled to share this work from my postdoc with Tom Carmichael, available online @ Neuron! Long story short: we find even more evidence that all reactive astrocytes are not equal, and we can take advantage of those differences to improve repair after stroke.
www.sciencedirect.com/science/arti...

Thrilled to share our new paper @cp-cell.bsky.social:
“Microglia–astrocyte crosstalk regulates synapse remodeling via Wnt signaling.”

This work demonstrates the necessity of glia–glia communication and coordination during synapse remodeling.

🔗 www.cell.com/cell/fulltex...

Faust et al., Cell 2025

I've been really hoping to see more manuscript threads here on 🦋, so here comes one!!! This is brand new work from the lab that took us in very unexpected directions and to exciting findings led by the amazing @emily-hill.bsky.social. Preprint here www.biorxiv.org/content/10.1...
and 🧵below:

Thanks, Ashley!!