Education & Certifications

  • B.S., University of Rochester, Neuroscience (2019)

All Publications

  • Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents SCIENCE TRANSLATIONAL MEDICINE Cho, F. S., Vainchtein, I. D., Voskobiynyk, Y., Morningstar, A. R., Aparicio, F., Higashikubo, B., Ciesielska, A., Broekaart, D. M., Anink, J. J., van Vliet, E. A., Yu, X., Khakh, B. S., Aronica, E., Molofsky, A., Paz, J. T. 2022; 14 (652): eabj4310


    Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown. Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury. In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury. Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway. Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.

    View details for DOI 10.1126/scitranslmed.abj4310

    View details for Web of Science ID 000823407900002

    View details for PubMedID 35857628

  • Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17. Nature Iram, T., Kern, F., Kaur, A., Myneni, S., Morningstar, A. R., Shin, H., Garcia, M. A., Yerra, L., Palovics, R., Yang, A. C., Hahn, O., Lu, N., Shuken, S. R., Haney, M. S., Lehallier, B., Iyer, M., Luo, J., Zetterberg, H., Keller, A., Zuchero, J. B., Wyss-Coray, T. 2022


    Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing1-3. Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds4,5. We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.

    View details for DOI 10.1038/s41586-022-04722-0

    View details for PubMedID 35545674

  • Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury SCIENCE Holden, S. S., Grandi, F. C., Aboubakr, O., Higashikubo, B., Cho, F. S., Chang, A. H., Forero, A., Morningstar, A. R., Mathur, V., Kuhn, L. J., Suri, P., Sankaranarayanan, S., Andrews-Zwilling, Y., Tenner, A. J., Luthi, A., Aronica, E., Corces, M., Yednock, T., Paz, J. T. 2021; 373 (6560): 1217-+


    [Figure: see text].

    View details for DOI 10.1126/science.abj2685

    View details for Web of Science ID 000695436000024

    View details for PubMedID 34516796