Microarray analysis to screen the related genes of venlafaxine on chronic mild stress rats

Abstract

Objective To used microarray analysis to screen the related genes of venlafaxine. Methods All rats were divided into 3 groups (6 rats per group) according to the table of random digit, i. e. , normal control, venlafaxine + stress, saline + stress. The rats of normal control group receive no intervention until otherwise noted. The stress group was subjected to the chronic mild stress procedure for 8 weeks. Rats in stress group were interfered with venlafaxine [(2. 5 mg/(kg · d)]and saline in weeks 5-8. Weight and sucrose intake were tested every week. At the end of weeks 8, all rats were sacrificed. Three rats in venlafaxine group were randomly chosen. Hippocampus of both sides from chosen venlafaxine group and saline group were collected and total RNA was abstracted. The cDNA probes of venlafaxine and saline control were prepared by labeling cell RNA with Cy5 and Cy3 with reverse transcription respectively. The microarrays with 10 891 genes were hybridized against the cDNA probe mixture, and the fluorescent signals were scanned. Results From weeks 1 to 8, the weights in normal control group [(365.4 ±22.5) ,(383. 1 ± 17. 2), (434. 1 ± 35. 7), (467. 0 ± 30. 3), (496. 2 ±34.4),(516. 2 ± 34. 4) , (534. 8 ± 44.4) , (535. 5 ± 35. 7) g] were significantly higher than that in venlafaxine +stress [(322. 3 ±9.5), (335. 6±13. 8), (348. 8 ± 18.9), (370.0 ±22. 6), (391.2 ±31. 2), (394.0 ±24.4),(401.6 ±26.9),(409.2 ±29.9) g]and saline + stress groups [(313.2 ± 14.5), (328.2 ±11. 1) ,(350. 9 ± 15. 6) ,(345. 3 ±29. 0), (370. 8 ±42. 9), (396. 0 ±45. 8), (395. 0 ±49. 2), (404. 5 ±38. 6) g, P = 0. 000]. In weeks 4, the level of sucrose intake in normal control group [(7. 7 ± 1. 1) g] was higher than that in venlafaxine + stress [(5. 0 ± 2. 5) g, P = 0. 046] and saline + stress groups [(4. 9 ±2.5) g, P = 0. 038]. From weeks 6 there was no difference on sucrose intake between venlafaxine + stress [(9. 4±5.2), (17.9 ±5.9), (18.9 ±5.5) g] and normal control groups [(13.4 ±2. 1), (15. 8 ±3. 8),(15. 7 ± 4. 4) g,P>0. 05] , both of which were higher than saline + stress group [(5. 3 ± 4. 3) , (4. 9 ±3. 9) , (4.7 ±2.9) g, P =0. 013,0. 000,0. 000]. Ten genes were up-regulated in all venlafaxine treated rats when the ratio of Cy5 /Cy3 signal was ≥ 2. 0 or ≤0. 5. Conclusions The mechanism of venlafaxine treatment related to many genes, which include neural development, neural plastically, ion channel, and transmembrane transporters. Key words: Oligonucleotide array sequence analysis; Hippocampus; Genes; Stress; Venlafaxine