title: Activation of Hippocampal CREB by Rolipram Partially Recovers Balance Between TNF-α and IL-10 Levels and Improves Cognitive Deficits in Diabetic Rats.
abstract: Diabetes damages the central nervous system, inducing cognitive dysfunction and structural changes, known as diabetic encephalopathy (DE). Some research suggests that the pathogenesis of DE may involve an inflammatory imbalance in the nervous system, along with β-amyloid deposition, similar to Alzheimer's disease. Less data have been yet provided to prove that mechanism. The aim of this study was to evaluate the influence of diabetes on the expression of TNF-α, IL-10, and cAMP response element-binding protein (CREB)/phosphorylated CREB (pCREB). Moreover, we investigated whether rolipram can improve memory, suppress the inflammatory response, and improve balance of CREB/pCREB in the hippocampus of diabetic rats. We used a 4-week high-fat diet and a low dose of streptozocin (30 mg/kg) to induce diabetes with hyperinsulinemia and hyperglycemia. Cognitive impairment was induced over a period of 4 months, and rolipram treatment was concomitantly given. Cognitive impairment was evaluated with the Morris water maze test. We also assessed expression of the pro-inflammatory cytokine TNF-α and the anti-inflammatory cytokine IL-10. We found that memory in rats with long-term diabetes was impaired. Treatment with rolipram increased expression of CREB and pCREB, reduced the inflammatory reaction (decreased TNF-α levels and increased IL-10 levels), and prevented cognitive impairment in these diabetic animals. This present study suggests that rolipram improves cognitive function by activating the CREB signaling pathway and alleviating neuroinflammation in type 2 diabetic rats. Rolipram may have therapeutic potential in DE.
authors.affiliation: Department of Geriatrics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Department of Geriatrics, Zhejiang Hospital, 12 Ling Yin Road, Hangzhou, 310013, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Geriatrics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Geriatrics, Shanghai Jiaotong 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 Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China.
authors.forename: Beiyuan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai, 200233, China. zhongyuan_zhy@163.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000819:agonists / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D016753:Interleukin-10 / Q000819:agonists / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020889:Rolipram
keywords: Cognitive impairment; Diabetes; Neuroinflammation; Rolipram