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Neuron‐specific caveolin‐1 overexpression improves motor function and preserves memory in mice subjected to brain trauma
Author(s) -
Egawa Junji,
Schilling Jan M.,
Cui Weihua,
Posadas Edmund,
Sawada Atsushi,
Alas Basheer,
ZemljicHarpf Alice E.,
FanPavlich McKenzie J.,
Mandyam Chitra D.,
Roth David M.,
Patel Hemal H.,
Patel Piyush M.,
Head Brian P.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601288rrr
Subject(s) - hippocampus , neuroscience , neuron , synapsin i , hippocampal formation , neuroplasticity , nmda receptor , transgene , genetically modified mouse , biology , synapse , receptor , medicine , biochemistry , vesicle , genetics , membrane , gene , synaptic vesicle
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