title: CART treatment improves memory and synaptic structure in APP/PS1 mice.
abstract: Major characteristics of Alzheimer's disease (AD) include deposits of β-amyloid (Aβ) peptide in the brain, loss of synapses, and cognitive dysfunction. Cocaine- and amphetamine-regulated transcript (CART) has recently been reported to attenuate Aβ-induced toxicity. In this study, CART localization in APP/PS1 mice was characterized and the protective effects of exogenous CART treatment were examined. Compared to age-matched wild type mice, 8-month-old APP/PS1 mice had significantly greater CART immunoreactivity in the hippocampus and cortex. A strikingly similar pattern of Aβ plaque-associated CART immunoreactivity was observed in the cortex of AD cases. Treatment of APP/PS1 mice with exogenous CART ameliorated memory deficits; this effect was associated with improvements in synaptic ultrastructure and long-term potentiation, but not a reduction of the Aβ plaques. Exogenous CART treatment in APP/PS1 mice prevented depolarization of the mitochondrial membrane and stimulated mitochondrial complex I and II activities, resulting in an increase in ATP levels. CART treatment of APP/PS1 mice also reduced reactive oxygen species and 4-hydroxynonenal, and mitigated oxidative DNA damage. In summary, CART treatment reduced multiple neuropathological measures and improved memory in APP/PS1 mice, and may therefore be a promising and novel therapy for AD.
authors.affiliation: 1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Jia-li
authors.initials: JL
authors.lastname: Jin
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Anthony K F
authors.initials: AK
authors.lastname: Liou
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Yejie
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Kai-lin
authors.initials: KL
authors.lastname: Yin
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: 1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Li
authors.affiliation: 1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: 1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: 1] Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China [2] The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004249:DNA Damage; D004272:DNA, Mitochondrial; D004195:Disease Models, Animal; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D058225:Plaque, Amyloid / Q000473:pathology; D013569:Synapses / Q000187:drug effects* / Q000473:pathology*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D016229:Amyloid beta-Peptides; D004272:DNA, Mitochondrial; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein