iiinova — where your digital self keeps evolving

I began this as a PhD student. Completing the story took an extraordinary team at Johns Hopkins. I’m deeply grateful to Akira Sawa, Dwight Bergles, and all our coauthors for their persistence and collaboration. @agarwal-neurolab.bsky.social @droligo.bsky.social @lnhayeslab.bsky.social 11/11

Questions I’m left with: How broadly does astrocyte metabolic redox tune neuronal excitability? Is the prelimbic cortex especially susceptible? Do similar redox/ion-homeostasis signatures appear in astrocyte datasets from mood or epilepsy models without overt oxidative stress or reactivity? 10/11

The implication extends beyond PDE. Psychiatric symptoms accompany epilepsy, but here they were not downstream of seizures. Astrocyte redox controlled prefrontal excitability independently of seizure susceptibility, suggesting redox/ion homeostasis may shape mood circuits in other conditions. 9/11

This may explain a clinical feature of PDE: vitamin B6 can control seizures, yet psychiatric and cognitive symptoms often persist. More broadly, co-occurring symptoms need not share a pathophysiology: even one mutation can act through different tissues to produce distinct symptom domains. 8/11

What about seizures? To our surprise, hepatocyte-specific ALDH7A1 deletion increased seizure susceptibility, whereas astrocyte deletion did not. How loss of ALDH7A1 in the liver changes brain metabolism and lowers seizure threshold remains unresolved. 7/11

The mechanistic split extended to treatment. In global KO mice with both seizure- and mood-related phenotypes, dietary sulforaphane—a broccoli-derived NRF2 activator studied in human trials—normalized prelimbic activity and affective behavior, but not seizure susceptibility. 6/11

Re-expressing ALDH7A1 or activating NRF2 selectively in adult astrocytes restored prelimbic neuronal activity. This argues against an irreversible developmental consequence: ongoing astrocyte redox dysfunction was maintaining the circuit phenotype. 5/11

Mechanistically, our data suggests excess astrocyte Na+/K+-ATPase activity → lower extracellular K+ → hyperpolarization and hypoactivity of prelimbic L5 pyramidal neurons. In acute slices, ouabain normalized activity, linking astrocyte redox/ion homeostasis to prelimbic circuit function. 4/11

The astrocyte KO revealed a key function for ALDH7A1 in astrocyte redox metabolism. Its loss shifted NAD+/NADH and glutathione balance. This redox shift did not cause overt oxidative stress or reactive gliosis; it altered redox-sensitive Ca2+ signaling and ion-transport programs. 3/11

Global ALDH7A1 KO mice had both phenotypes. Because ALDH7A1 is selectively expressed by astrocytes among major brain cell types, we expected astrocyte deletion to reproduce both. Instead, it reproduced the affective behaviors—but not seizure susceptibility. 2/11

Astrocyte redox imbalance underlies prelimbic neuronal hypoactivity and maladaptive affective behaviors in epilepsy

Do psychiatric symptoms in epilepsy always arise from seizures? In ALDH7A1 models, seizure risk traced to the liver; mood-related behavior to astrocytes. One gene. Two tissues. Two pathophysiologies. Neither begins in neurons. New in Science Advances: doi.org/10.1126/scia... 1/11

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Astrocyte antioxidant imbalance reduces neuronal activity, driving depression-like behavior in epilepsy dissociable from seizures.

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Reposted by Travis Faust

Danielle Adank, PhD @femmeinstem.bsky.social · 23/07/2026

🚨🚨ATTENTION NEUROSCIENCE POSTDOCS!!🚨🚨 UMass Chan’s Department of Neurobiology is searching for applicants for our inaugural UMass ChanNELS series! For more information and to apply: docs.google.com/forms/d/e/1F...

UMass Chan’s Department of Neurobiology is searching for applicants for our inaugural UMass ChanNELS series!

The purpose of this series is to give postdoctoral researchers experience giving a 50 minute presentation in an exciting and professional setting.

This seminar series will include:
A 50 minute presentation in front of the department Meetings with faculty Lunch with trainees One night hotel stay in Worcester, MA. **DISCLOSURE**
Hotel accommodation and on-campus hospitality are provided. Please note that travel to Worcester, MA is not funded at this time. Applicants should confirm they are able to arrange and cover their own transportation before applying.

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Travis Faust @travisfaust.bsky.social · 01/08/2026

I’m incredibly grateful to @simonsfoundation.org for supporting my research vision and the next stage of my scientific career. It is a tremendous honor to be selected for this award!

Travis Faust @travisfaust.bsky.social · 16/12/2025

Update: a Targetome commentary by Zhao, Agarwal & Bai discusses our Cell paper as part of a broader paradigm of glia–glia coordination—linking microglia–astrocyte signaling in synaptic pruning to cooperative glial mechanisms in processes such as myelination. www.maxapress.com/article/doi/...

maxapress.com

Glial Wnt dialogue controls synapses

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Reposted by Travis Faust

UMass Chan Medical School @umasschan.bsky.social · 07/10/2025

A study by Dorothy P. Schafer, PhD, and Travis E. Faust, PhD, in Cell explains how cell types in the brain communicate in response to changes in sensory input to remodel synapses: direc.to/nJHH Alzheimer’s and ALS patients have synaptic damage. @travisfaust.bsky.social @cp-cell.bsky.social

direc.to

UMass Chan scientists show how the non-neuronal brain cells communicate to coordinate rewiring of brain

A study by Dorothy P. Schafer, PhD, and Travis E. Faust, PhD, explains how two different cell types in the brain communicate in response to changes in sensory input.

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Travis Faust @travisfaust.bsky.social · 14/09/2025

Thanks so much! Dori has been a fantastic mentor - I’m glad you were able to connect with her 😊

Travis Faust @travisfaust.bsky.social · 13/09/2025

Ha, fair takeaway 🙂. Mice use whiskers a bit like we use our fingertips — trimming them helps us study how brain connections change when inputs go quiet. If you’re curious, here’s a short public talk I gave that starts broad and then dives into this work: youtu.be/Gb22qhBVfOA?...

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Science Café: Unlocking the Secrets of Brain Growth and Decline - How Glial Stem cell shape our Mind

YouTube video by UMass Chan Postdoc Association

Thanks so much! Really appreciate it 🙏

Thanks Lindsay! We're really excited to see where this work leads. It's great to see the growing interest in glia-glia interactions.

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🙏 Thanks to my mentor Dorothy Schafer, collaborators @caglaeroglu.bsky.social, @pinar-ayata.bsky.social, and Anne Schaefer, and all my co-authors. Proud to do this work at @umasschan.bsky.social. 💡 Excited to see where glial biology goes next!

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🔮 Open questions ahead: When do microglia release Wnt? What happens when astrocytes change how much they touch synapses in development, sleep, aging, or disease? Does less astrocyte contact generally make synapses easier for microglia to remove? How do microglia remove less-contacted synapses?

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We show that astrocytic Wnt signaling is also seen in: 💤 Sleep ⏳ Aging ⚡ Seizures 🧠 Alzheimer’s disease In these contexts, changes in astrocyte morphology & synapse loss have been reported, suggesting this pathway may be shared across brain states & disorders.

To reveal this pathway we used: 🧠 A defined cortical circuit model of activity-driven synapse loss 🔍 Expansion microscopy to map astrocyte–synapse contacts 🧬 TRAP-Seq + MERFISH to identify microglial Wnts ✂️ Cell type–specific knockouts to test signaling

Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling - Nature Neuroscience

After sensory deprivation we found: ⚡ Neurons signal to microglia via CX3CL1–CX3CR1 🔁 Microglia release Wnts, causing astrocytes to reduce synaptic contact 🧹 Reduced astrocyte–synapse contact allows microglia to remove synapses (Our prior work on CX3CL1/CX3CR1: doi.org/10.1038/s415...)

doi.org

Microglia are resident immune cells of the CNS. Here the authors show that neurons communicate to microglia via activity-dependent fractalkine and ADAM10 signaling to induce removal of synapses in the...

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🧩Both microglia and astrocytes can remove synapses. But their respective roles — and whether they act independently, redundantly, or in coordination — has been unclear. How do neurons, microglia, and astrocytes work together during synapse remodeling?