The Effect Of N-3 PUFAs On Spatial Learning And Memory In T2DM Rats

ObjectivesTo explore the effect of n-3 polyunsaturated fatty acids(PUFA)on spatial learning and memory in type 2 diabetes mellitus(T2DM)rats and the possible mechanism.MethodsSeventy male Sprague Dawley(SD)rats at four weeks of age were randomly divided into normal control(NC)and model groups(Mod).The NC group was fed with lab chow,and the Mod group was fed with high-fat & high-sugar diet for eight weeks.Intraperitoneal injection of 1% streptozotocin(35mg/kg)was induced in the rats in Mod group to estabolish T2 DM animal model.The diabetic rats were randomly divided into T2 DM group,fish oil low(FO-L),medium(FO-M),high-dose groups(FO-H)and corn oil group(CO).The FO-L,FO-M,FO-H were given with corresponding n-3 PUFAs dosages at 75 mg/kg,150 mg/kg,and 300 mg/kg respectively.The rats in CO group were gavaged with the same volume of corn oil,and those in NC and T2 DM groups were gavaged with the same volume of distilled water daily.After six weeks,the consumption of water and diet,as well as the urine discharge within 24 h were recorded and the density of urine was measured.The spatial learning and memory were tested through Morris water maze in the rats.Fasting serum glucose(FSG),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),C-reactive protein(CRP),interleukin-6(IL-6)and fasting insulin(FINS)were measured.The levels of c AMP-response element binding protein(CREB),brain-derived neurotrophic factor(BDNF)and Akt protein in hippocampal tissue of the rats in each group were detected via enzym-linked immunoassay.Hematoxylin eosin(HE)staining was used to observe the histological morphology of neurons in hippocampal CA1 region of the rats.SPSS 22.0 was used for statistical analysis.Results1.Compared with NC group,body weight of the rats in T2 DM group was significantly decreased(P<0.05),while the consumption of water & diet,the urine discharge,and the urine density were significantly increased in the rats of T2 DM group(P<0.05).2.The serum levels of FSG,FINS and HOMA-IR were higher,but HOMA-βwas lower in T2 DM group than that in NC group(P<0.05).The serum level FINS and HOMA-IR were lower in FO-L and FO-M groups than those in T2 DM group(P<0.05),and FSG,FINS and HOMA-IR were lower in FO-H group than those in T2 DM and CO groups(P<0.05).3.The levels of TG,TC and LDL-C were significantly higher,but HDL-C was significantly lower in T2 DM group rats than that in NC group(P<0.05).The serum level of HDL-C was significantly higher in FO-L group rats(P<0.05),while the levels of TG,TC and LDL-C were significantly lower in the rats of FO-M and FO-H groups than that in T2 DM group(P<0.05).The serum levels of TG were significantly lower in the rats of FO-M and FO-H groups than that in CO group(P<0.05).4.The serum levels of IL-6 and CRP were significantly higher in T2 DM group rats than that in NC and FO-L groups(P<0.05).5.The water maze test showed that the escape latency was significantly longer in the rats of T2 DM group than that in NC group.The escape latency was significantly shorter in the rats in FO-L,FO-M and FO-H groups than that in both T2 DM and CO groups(P<0.05).The probe test showed that the number of crossing platform was much less in the rats of T2 DM group that that in NC and FO-M and FO-H groups(P<0.05).6.The protein levels of Akt,CREB and BDNF in hippocampus were significantly lower in the rats of T2 DM group than that in NC group(P<0.05).The protein expression levels of Akt,CREB and BDNF were significantly higher in the rats of FO-M and FO-H groups and the level of Akt was also significantly higher in the rats of FO-L group than that in T2 DM group(P<0.05).The protein levels of Akt,CREB and BDNF were significantly higher in the rats of FO-H group(P<0.05)and the level of CREB was significantly higher in the rats in FO-M group than that in CO group(P<0.05).7.Compared with NC group,the number of neurons in CA1 region of hippocampus was remarkedly recuded and more incomplete cells,also missing nucleus were seen in the rats of T2 DM group.Compared with the rats in T2 DM and CO groups,the number of neurons were increased in that of FO-L,FO-M and FO-H groups,while the morphology and structure of neurons were significantly improved in the rats of FO-H group.Conclusions1.n-3 PUFAs could decline FSG,improve dyslipidemia and IR in T2 DM rats.2.n-3 PUFAs could decrease the serum levels of CRP and IL-6 and ease inflammation in T2 DM rats.3.n-3 PUFAs could improve the performance of spatial learning and memory in diabetic rats,which might be contributed by enhancing the expression of Akt,CREB and BDNF in the hippocampus and modifying the relevant signal pathway.