Journal article
CXCL12-induced rescue of cortical dendritic spines and cognitive flexibility
eLife, v 9, e49717
23 Jan 2020
PMID: 31971513
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Synaptodendritic pruning is a common cause of cognitive decline in neurological disorders, including HIV-associated neurocognitive disorders (HAND). HAND persists in treated patients as a result of chronic inflammation and low-level expression of viral proteins, though the mechanisms involved in synaptic damage are unclear. Here, we report that the chemokine CXCL12 recoups both cognitive performance and synaptodendritic health in a rodent model of HAND, which recapitulates the neuroinflammatory state of virally controlled individuals and the associated structural/functional deficiencies. CXCL12 preferentially regulates plastic thin spines on layer II/III pyramidal neurons of the medial prefrontal cortex via CXCR4-dependent stimulation of the Rac1/PAK actin polymerization pathway, leading to increased spine density and improved flexible behavior. Our studies unveil a critical role of CXCL12/CXCR4 signaling in spine dynamics and cognitive flexibility, suggesting that HAND - or other diseases driven by spine loss - may be reversible and upturned by targeting Rac1-dependent processes in cortical neurons.
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Details
- Title
- CXCL12-induced rescue of cortical dendritic spines and cognitive flexibility
- Creators
- Lindsay K Festa - Department of Pharmacology and Physiology Drexel University College of Medicine Center of Neuroimmunology and CNS Therapeutics, Institute of Molecular Medicine and Infectious Diseases Drexel University College of MedicineElena Irollo - Drexel University, Pharmacology and PhysiologyBrian J Platt - Drexel University, Pharmacology and PhysiologyYuzen Tian - Drexel UniversityStan Floresco - University of British ColumbiaOlimpia Meucci - Drexel University, Pharmacology and Physiology
- Publication Details
- eLife, v 9, e49717
- Publisher
- eLife Sciences Publications
- Grant note
- ; MH078795 / ; DA040519 / ; DA032444 / ; DA015014 / ;
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000513013800001
- Scopus ID
- 2-s2.0-85079094968
- Other Identifier
- 991014877877604721
UN Sustainable Development Goals (SDGs)
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Source: SDGs in the Output
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biology