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The FASEB Journal
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The FASEB Journal
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Neuron‐specific caveolin‐1 overexpression improves motor function and preserves memory in mice subjected to brain trauma

Authors: Junji, Egawa; Jan M, Schilling; Weihua, Cui; Edmund, Posadas; Atsushi, Sawada; Basheer, Alas; Alice E, Zemljic-Harpf; +6 Authors

Neuron‐specific caveolin‐1 overexpression improves motor function and preserves memory in mice subjected to brain trauma

Abstract

ABSTRACT Studies in vitro and in vivo demonstrate that membrane/lipid rafts and caveolin (Cav) organize progrowth receptors, and, when overexpressed specifically in neurons, Cav‐1 augments neuronal signaling and growth and improves cognitive function in adult and aged mice; however, whether neuronal Cav‐1 overexpression can preserve motor and cognitive function in the brain trauma setting is unknown. Here, we generated a neuron‐targeted Cav‐1–overexpressing transgenic (Tg) mouse [synapsin‐driven Cav‐1 (SynCav1 Tg)] and subjected it to a controlled cortical impact model of brain trauma and measured biochemical, anatomic, and behavioral changes. SynCav1 Tg mice exhibited increased hippocampal expression of Cav‐1 and membrane/lipid raft localization of postsynaptic density protein 95, NMDA receptor, and tropomyosin receptor kinase B. When subjected to a controlled cortical impact, SynCav1 Tg mice demonstrated preserved hippocampus‐dependent fear learning and memory, improved motor function recovery, and decreased brain lesion volume compared with wild‐type controls. Neuron‐targeted overexpression of Cav‐1 in the adult brain prevents hippocampus‐dependent learning and memory deficits, restores motor function after brain trauma, and decreases brain lesion size induced by trauma. Our findings demonstrate that neuron‐targeted Cav‐1 can be used as a novel therapeutic strategy to restore brain function and prevent trauma‐associated maladaptive plasticity.—Egawa, J., Schilling, J. M., Cui, W., Posadas, E., Sawada, A., Alas, B., Zemljic‐Harpf, A. E., Fannon‐Pavlich, M. J., Mandyam, C. D., Roth, D. M., Patel, H. H., Patel, P. M., Head, B. P. Neuron‐specific caveolin‐1 overexpression improves motor function and preserves memory in mice subjected to brain trauma. FASEB J . 31, 3403–3411 (2017). www.fasebj.org

Keywords

Male, Neurons, Neuronal Plasticity, Genotype, Caveolin 1, Mice, Transgenic, Fear, Genetic Therapy, Mice, Inbred C57BL, Mice, Gene Expression Regulation, Memory, Brain Injuries, Traumatic, Conditioning, Psychological, Animals

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    23
    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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Found an issue? Give us feedback
selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
23
Top 10%
Average
Top 10%
bronze