Targeting Astrocytes Ameliorates Neurologic Changes in a Mouse Model of Alzheimer's Disease

• DOI: 10.1523/jneurosci.2323-12.2012
• Publication Date: 2012-11-14T17:47:52Z
• Authors: Jennifer L. Furman; Diana M. Sama; John C. Gant; Tina L. Beckett; M. Paul Murphy; Adam D. Bachstetter; Linda J. Van Eldik; Christopher M. No...
• Keywords: Inflammation; 0301 basic medicine; NFATC Transcription Factors; Blotting, Western; Calcineurin Inhibitors; Long-Term Potentiation; Gene Transfer Techniques; Brain; Excitatory Postsynaptic Potentials; Enzyme-Linked Immunosorbent Assay; Mice, Transgenic; Dependovirus; Immunohistochemistry; 3. Good health; Mice; 03 medical and health sciences; Alzheimer Disease; Astrocytes; Avoidance Learning; Image Processing, Computer-Assisted; Animals; Humans; Cells, Cultured

Astrocytes are the most abundant cell type in brain and play a critical role maintaining healthy nervous tissue. In Alzheimer's disease (AD) other neurodegenerative disorders, many astrocytes convert to chronically "activated" phenotype characterized by morphologic biochemical changes that appear compromise protective properties and/or promote harmful neuroinflammatory processes. Activated emerge early course of AD become increasingly prominent as clinical pathological symptoms progress, but few studies have tested potential astrocyte-targeted therapeutics an intact animal model AD. Here, we used adeno-associated virus (AAV) vectors containing astrocyte-specific Gfa2 promoter target hippocampal APP/PS1 mice. AAV-Gfa2 drove expression VIVIT, peptide interferes with immune/inflammatory calcineurin/NFAT (nuclear factor activated T-cells) signaling pathway, shown our laboratory others orchestrate cascades leading astrocyte activation. After several months treatment Gfa2-VIVIT, mice exhibited improved cognitive synaptic function, reduced glial activation, lower amyloid levels. The results confirm deleterious for lay groundwork exploration novel astrocyte-based therapies.