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Research ArticleResearch Article: New Research, Disorders of the Nervous System

Gfap Mutation and Astrocyte Dysfunction Lead to a Neurodegenerative Profile with Impaired Synaptic Plasticity and Cognitive Deficits in a Rat Model of Alexander Disease

Robert F. Berman, Matthew R. Matson, Angelica M. Bachman, Ni-Hsuan Lin, Sierra Coyne, Alyssa Frelka, Robert A. Pearce, Albee Messing and Tracy L. Hagemann
eNeuro 10 March 2025, 12 (3) ENEURO.0504-24.2025; https://doi.org/10.1523/ENEURO.0504-24.2025
Robert F. Berman
1UC Davis M.I.N.D. Institute, University of California Davis, Davis, California 95816
2Department of Neurological Surgery, University of California Davis, Sacramento, California 95816
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Matthew R. Matson
1UC Davis M.I.N.D. Institute, University of California Davis, Davis, California 95816
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Angelica M. Bachman
1UC Davis M.I.N.D. Institute, University of California Davis, Davis, California 95816
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Ni-Hsuan Lin
3Institute of Molecular Medicine, College of Life Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
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Sierra Coyne
4Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705
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Alyssa Frelka
5Department of Anesthesiology, University of Wisconsin-Madison, Madison, Wisconsin 53705
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Robert A. Pearce
5Department of Anesthesiology, University of Wisconsin-Madison, Madison, Wisconsin 53705
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Albee Messing
4Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705
6Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706
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Tracy L. Hagemann
4Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705
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Article Information

DOI 
https://doi.org/10.1523/ENEURO.0504-24.2025
PubMed 
40064497
Published By 
Society for Neuroscience
History 
  • Received November 5, 2024
  • Revision received January 28, 2025
  • Accepted March 4, 2025
  • Published online March 10, 2025.
Copyright & Usage 
Copyright © 2025 Berman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Author Information

  1. Robert F. Berman1,2,
  2. Matthew R. Matson1,
  3. Angelica M. Bachman1,
  4. Ni-Hsuan Lin3,
  5. Sierra Coyne4,
  6. Alyssa Frelka5,
  7. Robert A. Pearce5,
  8. Albee Messing4,6 and
  9. Tracy L. Hagemann4
  1. 1UC Davis M.I.N.D. Institute, University of California Davis, Davis, California 95816
  2. 2Department of Neurological Surgery, University of California Davis, Sacramento, California 95816
  3. 3Institute of Molecular Medicine, College of Life Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
  4. 4Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin 53705
  5. 5Department of Anesthesiology, University of Wisconsin-Madison, Madison, Wisconsin 53705
  6. 6Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706
  1. Correspondence should be addressed to Tracy L. Hagemann at tlhagemann{at}wisc.edu.
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Author contributions

  1. Author contributions: R.F.B., R.A.P., A.M., and T.L.H. designed research; M.R.M., A.M.B., N.-H.L., S.C., A.F., and T.L.H. performed research; R.F.B., M.R.M., A.M.B., N.-H.L., S.C., A.F., R.A.P., and T.L.H. analyzed data; R.F.B., M.R.M., A.M.B., A.F., R.A.P., A.M., and T.L.H. wrote the paper.

Disclosures

  • The authors declare no competing financial interests.

  • This work was supported by grants from the NIH NINDS (NS110719 to T.L.H.), NICHD (HD076892 to A.M., HD105353 and HD090256 core grants to the Waisman Center, and HD103526 to the University of California M.I.N.D. Institute IDDRCs), NCI (CA014520 core grant to the University of Wisconsin Carbone Cancer Center), and NEI (EY016665 core grant for Vision Research at the University of Wisconsin-Madison); the Ralph M. Waters Distinguished Chair of Anesthesiology Fund (to R.A.P.); funds from the National Science and Technology Councils, Taiwan (NSTC 112-2917-I-007-007 to N.H.L.); and the Alexander Disease Research Fund. We thank Lauren Pedersen for her assistance with behavioral experiments at the UC Davis M.I.N.D. Institute IDDRC.

Funding

  • HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)

    NS110719
  • HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    HD076892; HD105353; HD090256; HD103526
  • HHS | NIH | National Cancer Institute (NCI)

    CA014520
  • HHS | NIH | National Eye Institute (NEI)

    EY016665
  • National Science and Techonology Councils, Taiwan

    NSTC 112-2917-I-007-007
  • The Ralph M. Waters Distinguished Chair of Anesthesiology Fund

  • The Alexander Disease Research Fund

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  • previous version (March 10, 2025).

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Gfap Mutation and Astrocyte Dysfunction Lead to a Neurodegenerative Profile with Impaired Synaptic Plasticity and Cognitive Deficits in a Rat Model of Alexander Disease
Robert F. Berman, Matthew R. Matson, Angelica M. Bachman, Ni-Hsuan Lin, Sierra Coyne, Alyssa Frelka, Robert A. Pearce, Albee Messing, Tracy L. Hagemann
eNeuro 10 March 2025, 12 (3) ENEURO.0504-24.2025; DOI: 10.1523/ENEURO.0504-24.2025

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Gfap Mutation and Astrocyte Dysfunction Lead to a Neurodegenerative Profile with Impaired Synaptic Plasticity and Cognitive Deficits in a Rat Model of Alexander Disease
Robert F. Berman, Matthew R. Matson, Angelica M. Bachman, Ni-Hsuan Lin, Sierra Coyne, Alyssa Frelka, Robert A. Pearce, Albee Messing, Tracy L. Hagemann
eNeuro 10 March 2025, 12 (3) ENEURO.0504-24.2025; DOI: 10.1523/ENEURO.0504-24.2025
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Keywords

  • astrocyte
  • hippocampus
  • innate immune response
  • long-term potentiation
  • mitochondria
  • synapse

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