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

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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; [5]Univ Calif San Diego, Dept Anesthesiol, VASDHS 9125,3350 La Jolla Village Dr, San Diego, CA 92161 USA
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关键词: neuroprotection MLRs hippocampus fear conditioning inverted grid

摘要:
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.

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出版当年[2016]版:
大类 | 2 区 生物
小类 | 2 区 生化与分子生物学 2 区 生物学 3 区 细胞生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 生物学 3 区 细胞生物学
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出版当年[2015]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 BIOLOGY Q1 CELL BIOLOGY
最新[2023]版:
Q1 BIOLOGY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CELL BIOLOGY

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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
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