Journal article
CXCL12-induced rescue of cortical dendritic spines and cognitive flexibility
eLife, v 9
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.
Metrics
Details
- Title
- CXCL12-induced rescue of cortical dendritic spines and cognitive flexibility
- Creators
- Lindsay K Festa - Center of Neuroimmunology and CNS Therapeutics, Institute of Molecular Medicine and Infectious Diseases, Drexel University College of Medicine, Philadelphia, United StatesElena Irollo - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, United StatesBrian J Platt - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, United StatesYuzen Tian - Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, United StatesStan Floresco - Department of Psychology, University of British Columbia, Vancouver, CanadaOlimpia Meucci - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, United States
- Publication Details
- eLife, v 9
- Publisher
- eLife; England
- Grant note
- R01 DA015014 / NIDA NIH HHS MH078795 / NIMH NIH HHS DA015014 / NIDA NIH HHS DA032444 / NIDA NIH HHS R37 DA015014 / NIDA NIH HHS DA040519 / NIDA NIH HHS
- 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)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biology