Effect Of Curcumin On Hippocampal No-Nos System Of Growing Pigs Subjected To Transport Stress

Previous studies demonstrated that stress causes dysfunction of hippocampus, and leads to neuron death which eventually results in a variety of neurodegenerative diseases. Lipopolysaccharide (LPS) or kainic acid (KA)-induced acute hippocampal neurodegenesis are associated with activation of hippocampal NO-NOS system. Studies on rodents indicated that curcumin (CUR) can alleviate the chronic stress and attenuates neuronal damage induced by LPS or KA through regulating hippocampal NO synthesis. The short distance transport is a subacute stress in pigs. It is not clear whether 2 h transport can induce activation of hippocampal NO-NOS system, and whether CUR may alleviate transport stress-induced responses in hippocampal NO-NOS system in pigs. Herein, this study was aimed to investigate (1) whether 2 h transport could lead to activation of hippocampal NO-NOS system in pigs; (2) whether feeding CUR for 21 days could reverse or attenuate stress-induced changes in hippocampal NO-NOS system in pigs; (3) whether CUR plays direct protective roles on primary porcine hippocampal neurons under the challenge of dexamethasone (DEX) in vitro.1 Effects of CUR on hippocampal NO-NOS system in pigs subjected to transport stress18 male Pietrain×Erhualian F2 piglets were randomly divided into three groups: control group (CON) fed basic diet for 21 d, tranport control group (T-CON) fed basal diet for 21 d, then subjected to 2 h transport, CUR group (CUR) was administered orally 8 mg/kg.BW of CUR per day successively for 21 d, then subjected to 2 h transport together with T-CON. After 2 h transport, piglets were sacrificed with electric shock. Serum and hippocampus were collected for analysing serum cortisol levels and variations in hippocampal NO-NOS system.2 h tranport significantly increased serum cortisol level (P< 0.01), CUR effectively attenuated transport stress-induced elevation of serum cortisol production (P<0.05). Transport led to significant increase of NO production in hippocampus (P<0.05), together with significantly (P<0.05) enhanced hippocampal mRNA expression of nNOS and eNOS, as well as increased (P< 0.05) activity of T-NOS, iNOSand cNOS. CUR totally reversed stress-induced hippocampal NO production, which was in line with completely reversed cNOS activity, and diminished mRNA expression of nNOS and eNOS, as well as T-NOS activity. The results indicated that CUR reverses or attenuates the activation of hippocampal NO-NOS induced by transport stress in pigs.2 Effect of curcumin pretreatment on viability and NO-NOS system of primary cultural hippocampal neurons exposed to dexamethasoneThe neuroprotective roles of CUR pretreatment was investigated in primary culture of porcine hippocampal neurons exposed to DEX for 24 h. Cell viability was detected by MTT assay and NO production in culture medium and NOS activity in cell lysates were determined with NO assay kit and NOS assay kit respectively. Cell viability was significantly decreased in DEX-treated neurons (P< 0.05),24 h of pretreatment with 10 p.M CUR reversed DEX-induced decrease in cell viability. DEX exposure resulted in significant increase in NO level in hippocampus (P<0.05), which was associated with up-regulated enzyme activities of T-NOS, iNOS and cNOS (P<0.05). CUR pretreatment prevented DEX-induced NO production and T-NOS, cNOS activation (P<0.05), but not iNOS up-regulation. The results indicated that CUR plays direct neuroprotective roles in primary hippocampal neurons under DEX challenge through modulating NO-NOS system.