CART treatment improves memory and synaptic structure in APP/PS1 mice

• Published in: Scientific reports 2015-05, Vol.5 (1), p.10224, Article 10224
• Main Authors: Jin, Jia-li, Liou, Anthony K.F., Shi, Yejie, Yin, Kai-lin, Chen, Ling, Li, Ling-ling, Zhu, Xiao-lei, Qian, Lai, Yang, Rong, Chen, Jun, Xu, Yun
• Format: Article
• Language: English
• Subjects: 13/106; 13/51; 14/28; 14/34; 4-Hydroxynonenal; 631/378/2611; 692/699/375/132; 82/58; 82/80; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - psychology; Alzheimer's disease; Amphetamines; Amyloid beta-Peptides - metabolism; Amyloid precursor protein; Animals; Brain - metabolism; Brain - pathology; Case-Control Studies; Cocaine; Cocaine- and amphetamine-regulated transcript protein; Cognitive ability; Depolarization; Disease Models, Animal; DNA Damage; DNA, Mitochondrial; Electron transport chain; Gene Expression; Hippocampus; Hippocampus - metabolism; Humanities and Social Sciences; Humans; Immunoreactivity; Localization; Long-term potentiation; Membrane potential; Memory; Memory - drug effects; Mice; Mice, Transgenic; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; multidisciplinary; NADH-ubiquinone oxidoreductase; Nerve Tissue Proteins - administration & dosage; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurites - drug effects; Neurites - metabolism; Neurodegenerative diseases; Neurotransmitter Agents - administration & dosage; Neurotransmitter Agents - genetics; Neurotransmitter Agents - metabolism; Oxidative Stress - drug effects; Plaque, Amyloid - pathology; Reactive oxygen species; Rodents; Science; Senile plaques; Synapses; Synapses - drug effects; Synapses - pathology; Toxicity; Transcription; Ultrastructure; β-Amyloid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep10224

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.