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Objective To investigate the effect and mechanism of suberoylanilide hydroxamic acid (SAHA) on the fear extinction in mice with chronic social defeat stress (SD). Methods Fifty-six male C57BL/6J mice aged 7-8 weeks were randomly divided into control group,social defeat group,control-SAHA group and social defeat-SAHA group to investigate the effect of SAHA and social defeat group,social defeat-AAV BDNF group and social defeat-AAV blank group to investigate the effect of BDNF. Fear extinction in mice was evaluated by fear conditioning test (FC). The levels of BDNF and HDAC2 in mice hippocampus were detected by Western blot (WB). The expression of BDNF-overexpressing virus in hippocampus of mice was detected by immunofluorescence assay. Results (1) Compared with control group,fear extinction in the social defeat group was significantly decreased (P<0. 05). Compared with control group, the level of HDAC2(0. 50±0. 02) in the social defeat group was significantly increased (P<0. 001),while the level of BDNF(0. 16 ± 0. 03) was significantly decreased (P<0. 001) in the social defeat group. ( 2) After using SAHA,fear extinction of mice significantly improved (P<0. 05). Compared with control group,the level of HDAC2 (0. 26±0. 02) in the control-SAHA group was significantly decreased(P<0. 001),and the level of BDNF (0. 40±0. 03) was significantly increased (P<0. 001). Compared with social defeat group,the level of HDAC2 (0. 39±0. 03) in the social defeat-SAHA group was significantly decreased (P<0. 001),and the lev-el of BDNF (0. 28±0. 01) was significantly increased (P<0. 001). (3)After injection BDNF-overexpressing virus,fear extinction was significantly improved(P<0. 05). Conclusion SAHA can enhance fear extinction in mice with chronic social defeat stress and its mechanism may be related to the up-regulation of BDNF ex-pression in hippocampus by inhibiting HDAC2 in hippocampal.
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Objective To investigate the neuroprotective effects of protease-activated receptor (PAR)-1 antagonist SCH79797 on early stage of brain injury and expression patterns of brain-derived neuro trophic factor (BDNF) and nerve growth factor (NGF) after subarachnoid hemorrhage (SAH) in rats. Methods Fifty-four clean male SD rats were randomly divided into three groups:sham-operative group, SAH group and treatment group (n=18). SAH rat models in the later two groups were induced by single cisterna magna blood injection. Rats in the treatment group were given SCH79797 (25μg/kg) after SAH modeling. Neurologic function was assessed and scored after SAH for 24 h. Then the rats were sacrificed, and then, the brains were collected for determination of brain water content. The expression patterns of BDNF and NGF in cerebral tissues were tested by enzyme linked immunosorbent assay and immunofluorescence method. Results As compared with rats in the SAH group, rats in the treatment group had significantly increased neurological deficit scale scores (12.11 ±2.62 vs. 14.59 ±2.24), statistically decreased water content in brain tissues (83.01%±0.38%vs. 79.79%±0.44%), with significant difference (P<0.05). As compared with those in the SAH group, the expressions of BDNF and NGF in treatment group were significantly higher ([100.15±59.13] pg/mL vs. [368.00±137.52] pg/mL; [33.44± 2.21] pg/mL vs. [37.49±2.29] pg/mL, P<0.05). As compared with those in the SAH group, the immunofluorescent staining intensities of BDNF and NGF in treatment group were significantly higher (41.65±1.50 vs. 91.40±1.30;23.50±1.70 vs. 30.65±1.80, P<0.05). Conclusion SCH79797 given early may reduce the degree of brain edema and increase the expressions of BDNF and NGF, which has obvious neuroprotective effect.
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Objective To observe the effects of Jiaji electroacupuncture and neurodynamic mobilization technique on axon regeneration and content of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in rabbits with sciatic nerve injury. Meth-ods 30 male adult rabbits were assigned to sham (A, n=6), model (B, n=6), neurodynamic mobilization (C, n=6), Jiaji electroacupuncture (D, n=6), and Jiaji electroacupuncture combine with neurodynamic mobilization (E, n=6) groups. The group C was treated with neurodynam-ic mobilization, the group D with Jiaji electroacupuncture, and the group D with both 3 days after modeling of clamping at sciatic nerve, while the groups A and B with no treatment. The axon regeneration was observed with HE staining, and the content of BDNF and CNTF in serum was measured with ELISA 4 weeks after treatment. Results The axons regeneration was observed better in the groups C, D and E than in the group B. The content of BDNF and CNTF was more in the groups C, D and E than in the group B (P<0.05). Conclusion Both Ji-aji electroacupuncture and neurodynamic mobilization can improve axon regeneration with synergistic action, which may associate with the increase of BDNF and CNTF in serum.