机构:[1]Vet Affairs San Diego Healthcare Syst, San Diego, CA USA;[2]Univ Calif San Diego, Sch Med, Dept Anesthesiol, La Jolla, CA 92093 USA;[3]Nara Med Univ, Dept Anesthesiol, Kashihara, Nara, Japan;[4]Capital Med Univ, Beijing Tiantan Hosp, Dept Anesthesiol, Beijing, Peoples R China;诊疗科室麻醉科首都医科大学附属天坛医院[5]Univ Calif San Diego, Dept Anesthesiol, VASDHS 9125,3350 La Jolla Village Dr, San Diego, CA 92161 USA
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.
基金:
Department of Veterans AffairsUS Department of Veteran Affairs [BX001225, BX000783, BX001963]; U.S. National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke Grant [NS073653]; NIH National Heart, Lung, and Blood InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HL091071, HL107200, HL066941, HL115933]; NIH National Institute on Drug Abuse Grant [DA034140]
第一作者机构:[1]Vet Affairs San Diego Healthcare Syst, San Diego, CA USA;[2]Univ Calif San Diego, Sch Med, Dept Anesthesiol, La Jolla, CA 92093 USA;[3]Nara Med Univ, Dept Anesthesiol, Kashihara, Nara, Japan;
通讯作者:
通讯机构:[1]Vet Affairs San Diego Healthcare Syst, San Diego, CA USA;[2]Univ Calif San Diego, Sch Med, Dept Anesthesiol, La Jolla, CA 92093 USA;[5]Univ Calif San Diego, Dept Anesthesiol, VASDHS 9125,3350 La Jolla Village Dr, San Diego, CA 92161 USA
推荐引用方式(GB/T 7714):
Egawa Junji,Schilling Jan M.,Cui Weihua,et al.Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma[J].FASEB JOURNAL.2017,31(8):3403-3411.doi:10.1096/fj.201601288RRR.
APA:
Egawa, Junji,Schilling, Jan M.,Cui, Weihua,Posadas, Edmund,Sawada, Atsushi...&Head, Brian P..(2017).Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma.FASEB JOURNAL,31,(8)
MLA:
Egawa, Junji,et al."Neuron-specific caveolin-1 overexpression improves motor function and preserves memory in mice subjected to brain trauma".FASEB JOURNAL 31..8(2017):3403-3411