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

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.

• Authors: Junji Egawa, Jan M Schilling, Weihua Cui, Edmund Posadas, Atsushi Sawada, Basheer Alas, Alice E Zemljic-Harpf, McKenzie J Fannon-Pavlich, Chitra D Mandyam, David M Roth, Hemal H Patel, Piyush M Patel, Brian P Head
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 31 Issue 8 Pg. 3403-3411 (08 2017) ISSN: 1530-6860 [Electronic] United States
• PMID: 28450301 (Publication Type: Journal Article)
• Copyright: © FASEB.

Chemical References

• Caveolin 1

Topics

• Animals
• Brain Injuries, Traumatic (metabolism, physiopathology)
• Caveolin 1 (genetics, 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)