PMID- 28466254 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20220321 IS - 1559-1166 (Electronic) IS - 0895-8696 (Print) IS - 0895-8696 (Linking) VI - 62 IP - 2 DP - 2017 Jun TI - Celecoxib Alleviates Memory Deficits by Downregulation of COX-2 Expression and Upregulation of the BDNF-TrkB Signaling Pathway in a Diabetic Rat Model. PG - 188-198 LID - 10.1007/s12031-017-0922-0 [doi] AB - Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed. Western blotting and immunohistochemical staining were performed to determine cyclooxygenase 2 (COX-2) expression in hippocampus. The results showed that a rat model of STZ-induced diabetes was successfully established and that celecoxib treatment significantly improved the associated nephropathy and inflammation. Moreover, spatial memory and hippocampal long-term potentiation (LTP) were impaired in diabetic model (P < 0.05). Interestingly, our data revealed that oral application of celecoxib reversed the memory deficit and hippocampal LTP in the diabetic rats. To understand the underlying mechanisms, the expression of some important pathways involved in memory impairment was determined. We found that brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase (p-TrkB) were decreased in diabetic rats but were effectively reversed by celecoxib treatment. As evidenced by western blotting and immunohistochemical staining, the expression of COX-2 in hippocampus was significantly upregulated in diabetic rat (P < 0.05) but inhibited by celecoxib treatment. The present findings provide novel data that celecoxib reverses memory deficits via probable downregulation of hippocampal COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a diabetic rat. FAU - Yang, Ying AU - Yang Y AD - Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangcheng District, Xiangyang City, Hubei, 441021, China. FAU - Gao, Ling AU - Gao L AD - Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No. 136, Jingzhou Street, Xiangcheng District, Xiangyang City, Hubei, 441021, China. linggao048@sina.com. LA - eng PT - Journal Article DEP - 20170502 PL - United States TA - J Mol Neurosci JT - Journal of molecular neuroscience : MN JID - 9002991 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclooxygenase 2 Inhibitors) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - EC 2.7.10.1 (Receptor, trkB) RN - JCX84Q7J1L (Celecoxib) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Celecoxib/pharmacology/*therapeutic use MH - Cyclooxygenase 2/*genetics/metabolism MH - Cyclooxygenase 2 Inhibitors/pharmacology/*therapeutic use MH - Diabetes Mellitus, Experimental/*drug therapy MH - Hippocampus/drug effects/metabolism/physiology MH - Long-Term Potentiation MH - *Memory MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, trkB/genetics/*metabolism MH - Signal Transduction PMC - PMC5486519 OTO - NOTNLM OT - BDNF-TrkB signaling OT - COX-2 OT - Celecoxib OT - Diabetes OT - Long-term potentiation OT - Memory deficit COIS- The author(s) declare(s) that there is no conflict of interest. EDAT- 2017/05/04 06:00 MHDA- 2018/03/27 06:00 PMCR- 2017/05/02 CRDT- 2017/05/04 06:00 PHST- 2016/11/21 00:00 [received] PHST- 2017/04/13 00:00 [accepted] PHST- 2017/05/04 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2017/05/04 06:00 [entrez] PHST- 2017/05/02 00:00 [pmc-release] AID - 10.1007/s12031-017-0922-0 [pii] AID - 922 [pii] AID - 10.1007/s12031-017-0922-0 [doi] PST - ppublish SO - J Mol Neurosci. 2017 Jun;62(2):188-198. doi: 10.1007/s12031-017-0922-0. Epub 2017 May 2.