Title: The new PDE4 inhibitor Roflupram ameliorated cognitive deficits and neuroinflammation in a rat model of Alzheimer's disease
Abstract: Aim To investigate whether the new PDE4 inhibitor Roflupram can ameliorate Aβ25- 35 induced cognitive deficits through the anti-neuroinflammation effects. Methods The Alzheimer 's disease model was produced by microinjection of amyloid-β( Aβ)25- 35 fibrils into the bilateral hippocampal CA1 area of male rats. Then the rats were randomly divided into shamoperated control group,Aβ25- 35 microinjected group,Aβ25- 35 microinjected followed by donepezil hydrochloride or Rolipram treated group,Aβ25- 35 microinjected combined Roflupram treated group with different doses.Treatment was given( i. g.) 24 h after microinjection surgery operation for consecutive 23 days. Morris water maze and passive avoidance test were used to test the behavior performance after drug treatments of 14 and20 days. The protein level of c AMP downstream signaling molecules( p-PKA,P-CREB), proinflammatory cytokines( i NOS,COX-2,TNF-α,IL-1β),microglia and astrocyte activation marker( Iba-1,GFAP) and inflammation related protein( nuclear NF-κB p65,pp38) in hippocampus were detected by Western blot.The mRNA level of proinflammatory cytokines was measured by semi-quantitative PCR. Results The results of behavioral manifestations indicated that Roflupram could significantly ameliorate the spatial learning and memory ability and the passive avoidance learning and memory ability impairment induced by microinjection of Aβ25- 35. Biochemical analysis revealed that the hippocampus protein level of p-CREB and p-PKA of rats was significantly decreased induced by microinjection of Aβ25- 35,while the level of NF-κBp65( Nucleus),p-p38,i NOS,COX-2,TNF-α,IL-1β,GFAP and Iba-1 was increased,and these effects were reversed by each kind of drug treatment. Semi-quantitative PCR test showed that each treatment could reduce the mRNA level of proinflammatory cytokines compared to the Aβ25- 35 microinjection animal. Conclusion The new PDE4 inhibitor Roflupram can ameliorate cognitive impairment induced by Aβ25- 35 infusion rat,which is related to its antigliosis,inflammatory cytokines expression reducing and neuroinflammation amelioration effect.
Publication Year: 2015
Publication Date: 2015-01-01
Language: en
Type: article
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