title: Rolipram-induced improvement of cognitive function correlates with changes in hippocampal CREB phosphorylation, BDNF and Arc protein levels.
abstract: Diabetics suffer from a higher risk of cognitive decline. cAMP response element-binding protein (CREB) is a transcription factor associated with memory and synaptic plasticity. Here, we investigated the molecular changes in the hippocampus correlated with diabetes associated cognitive decline (DACD) from a CREB-centered perspective in a rat model of type 2 diabetes. Furthermore, we tested the therapeutic effect of rolipram on DACD. High-fat diet and low-dose streptozocin were adopted to induce diabetes in SD rats. Results show that supplementation with rolipram for 23 days (0.5mg/kg, once a day) improved the performance of diabetic rats in Morris water navigation task with increased level of CREB, brain-derived neurotrophic factor (BDNF), and Arc protein in the hippocampus. Rolipram, acting as an inhibitor of PDE4, was found to repair the imbalance in the CREB/BDNF/Arc pathway. This study may provide important insights into the mechanisms underlying DACD and provide new therapeutic targets for clinical treatment.
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Boxi medical center, The First Affiliated Hospital of Soochow University, No. 188 Shizi St, Suzhou, Jiangsu 215006, China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Geriatrics, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China. Electronic address: nning-my@163.com.
authors.forename: Ya
authors.initials: Y
authors.lastname: Miao
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000523:psychology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism*; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology* / Q000627:therapeutic use; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D009124:Muscle Proteins; C491788:Nol3 protein, rat; D058988:Phosphodiesterase 4 Inhibitors; D020889:Rolipram
keywords: Arc protein; Brain-derived neurotrophic factor; Cognition; Rolipram; cAMP response element-binding protein