Meloxicam Improves Cognitive Impairment of Diabetic Rats through COX2-PGE2-EPs-cAMP/pPKA Pathway.
Mol Pharm
; 15(9): 4121-4131, 2018 09 04.
Article
in En
| MEDLINE
| ID: mdl-30109938
ABSTRACT
Diabetics often face greater risk of cognitive impairment than nondiabetics. However, how to prevent this disease is still unconfirmed. In this study, we investigated the potential protection and mechanism of meloxicam on cognitive impairment in diabetic rats. The diabetic rat model was established with a high-fat diet and a small dose of streptozotocin (40 mg/kg). The changes of spatial learning and memory, histopathology, and the protein expressions of amyloid protein precursor (APP) and ß-amyloid (Aß) indicated that diabetic rats had neuronal injury and cognitive impairment. Tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C reactive protein (CRP) and prostaglandin E2 (PGE2) levels, and microglial cell number were significantly increased in the diabetic rat brain. Meanwhile, the protein expressions of APP, Aß, cyclooxygenases2 (COX2), E-type prostanoid recptors 1 (EP1) and EP2, and the level of cyclic adenosine monophosphate (cAMP) were significantly increased, while the protein expressions of EP3 and phosphorylated protein kinase A (pPKA) were significantly decreased in the diabetic rat hippocampus and cortex. However, the EP4 protein expression had no significant changes. Meloxicam significantly improved neuronal injury and cognitive impairment, and significantly decreased inflammatory cytokines levels. Meloxicam also significantly decreased the protein expressions of APP, Aß, COX2, EP1 and EP2, and the level of cAMP and significantly increased the EP3 and pPKA protein expressions in rat hippocampus and cortex. However, meloxicam did not significantly influence the levels of blood glucose, lipids, and insulin of rats. Our results suggest that meloxicam could significantly protect diabetic rats from cognitive impairment via a mechanism that may be associated with rebalancing the COX2-PGE2-EPs-cAMP/PKA pathway.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cyclic AMP-Dependent Protein Kinases
/
Cyclic AMP
/
Cyclooxygenase 2
/
Cognitive Dysfunction
/
Meloxicam
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mol Pharm
Journal subject:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Year:
2018
Document type:
Article
Affiliation country:
China