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Rolipram-induced improvement of cognitive function correlates with changes in hippocampal CREB phosphorylation, BDNF and Arc protein levels
- Source :
- Neuroscience Letters. 610:171-176
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Spatial Learning
Muscle Proteins
Hippocampus
CREB
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
03 medical and health sciences
Cognition
0302 clinical medicine
Neurotrophic factors
Internal medicine
medicine
Animals
Phosphorylation
Cognitive decline
Cyclic AMP Response Element-Binding Protein
Maze Learning
Rolipram
Brain-derived neurotrophic factor
Arc (protein)
biology
Brain-Derived Neurotrophic Factor
General Neuroscience
Memory, Short-Term
030104 developmental biology
Endocrinology
Diabetes Mellitus, Type 2
Synaptic plasticity
biology.protein
Phosphodiesterase 4 Inhibitors
Apoptosis Regulatory Proteins
Cognition Disorders
Psychology
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 03043940
- Volume :
- 610
- Database :
- OpenAIRE
- Journal :
- Neuroscience Letters
- Accession number :
- edsair.doi.dedup.....248a85b663e6ef1fa610ddf7fe8013d6