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

FASEB J. 2017 Aug;31(8):3403-3411. doi: 10.1096/fj.201601288RRR. Epub 2017 Apr 27.


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.

Keywords: MLRs; fear conditioning; hippocampus; inverted grid; neuroprotection.

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / physiopathology
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Conditioning, Psychological
  • Fear
  • Gene Expression Regulation / physiology
  • Genetic Therapy
  • Genotype
  • Male
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuronal Plasticity / physiology
  • Neurons / metabolism*


  • Caveolin 1