Effects of vagus nerve stimulation on inflammatory factors and apoptosis in depression model rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective To explore the influence of vagus nerve stimulation (VNS) on inflammatory factors in serum and nucleus of the solitary tract,and hippocampal apoptosis in rats with depression induced by chronic unpredictable stress ( CUS). Methods Totally 32 male Sprague Dawley ( SD) rats aged 8-9 weeks were selected. Eight rats were chosen as control group,and the other 24 rats were treated as the de-pression model with CUS. The rats were randomly divided into CUS,fluoxetine and VNS group,with 8 rats in each group after successful modeling. The control group and CUS group were induced by normal saline. Flu-oxetine group and VNS group were implanted with VNS stimulation electrode. The VNS stimulation lasted for 28 d. On the time points of before experiment,after modeling and after treatment,the sucrose consumption test and open-field test (OFT) were performed to observe the behavioral changes of rats. Elisa was used to detect the levels of TNF-α,IL-6 and IL-1β in serum and nucleus of the solitary tract. Cell apoptosis was ob-served with TUNEL staining in hippocampal CA1 region. Results ( 1) Sucrose consumption experiment and OFT showed that,compared with the CUS group,the consumption of sucrose,percentage of sucrose con-sumption,scores of vertical and horizontal movement increased significantly in the VNS group ( consumption of sucrose (11. 78±2. 67) ml,(8. 06±2. 85) ml; percentage of sucrose consumption (72. 31±9. 98)%, (63. 67±8. 95)%; score of vertical movement (16. 61±3. 98),(10. 31±3. 86); score of horizontal move-ment (44. 25±9. 59),(36. 21±7. 21)) (t=4. 87,7. 98,5. 87,9. 12,all P<0. 05). There was no signifi-cant difference between VNS and fluoxetine groups (consumption of sucrose (11. 32±2. 66) ml; percentage of sucrose consumption (71. 31±9. 03)%; score of vertical movement (15. 63±4. 11); score of horizontal movement (45. 61±8. 54)) (t=-0. 32,-1. 83,0. 98,-1. 13,all P>0. 05). (2) Compared with the CUS group,levels of TNF-α,IL-6 and IL-1β in serum decreased in the VNS group ( serum TNF-α ( 46. 72 ± 11. 63) pg/ml,(125. 47±15. 18) pg/ml; serum IL-6 (243. 65±38. 90) pg/ml,(441. 39±83. 31) pg/ml;serum IL-1β (209. 31±32. 45) pg/ml,(339. 21±76. 37) pg/ml) (t=-70. 38,-196. 25,-131. 13,all P<0. 05). The results in the VNS group were lower than those in the fluoxetine group (serum TNF-α (58. 76 ±12. 64) pg/ml; serum IL-6 (308. 83± 64. 31) pg /ml,serum IL-1β ( 249. 18 ± 43. 6) pg/ml) ( t=-15. 38,-64. 25,-18. 83,both P<0. 05). The levels of TNF-α,IL-6 and IL-1β in nucleus of the solitary tract in the VNS group were lower than those in the CUS ( TNF-α (53. 52± 12. 31) pg/ml,(135. 51± 20. 64)pg/ml; IL-6 (265. 31±45. 63) pg/ml,(465. 32±60. 21) pg/ml; IL-1β (212. 66±43. 32)pg/ml, (365. 96±76. 32) pg/ml) (t=-79. 38,-189. 13,-127. 50,all P<0. 05) and fluoxetine groups (TNF-α(63. 42±10. 64) pg/ml; IL-6 (315. 62±53. 21) pg/ml; IL-1β (278. 32±65. 38) pg/ml ) (t=-10. 25,-39. 00,-83. 00,all P<0. 05). (3) The apoptotic rate of hippocampal CA1 region in VNS group ((21. 41± 5. 86)%) was lower than that in the CUS group ((32. 78±8. 32)%) (t=-10. 75,P<0. 05); and there was no difference between VNS group and fluoxetine group ((22. 54±6. 31)%) (t=-1. 75,P>0. 05). Conclu-sion VNS can improve the depression behavior in rats with depression induced by CUS and the mechanism maybe related to inhibiting the expression of TNF-α,IL-6 and IL-1β in serum and nucleus of the solitary tract and cell apoptosis in hippocampal CA1 region.