PMID- 26339395 OWN - NLM STAT- MEDLINE DCOM- 20160607 LR - 20181113 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 8 IP - 7 DP - 2015 TI - Cerebellar neuronal apoptosis in heroin-addicted rats and its molecular mechanism. PG - 8260-7 AB - BACKGROUND: The overall objective of this study was to investigate neuronal apoptosis and expression of apoptosis related proteins (c-jun, cytc and Bax) in the cerebellum of rates with heroin addiction. MATERIAL/METHODS: 40 adult male Sprague-Dawley rats which weighing 200-220 g were randomly divided into 5 groups (n = 8 per group): control group, 10-day heroin-addicted group, 20-day heroin-addicted group, 30-day heroin-addicted group and 40-day heroin-addicted group. Rats in the control group were treated with normal saline. Rats in the addiction groups (20 d, 30 d, 40 d) were all given subcutaneous injection with heroin for 15 days to induce heroin addiction. After injected with heroin for 15 days, rats were treated with naloxone at a dose of 5 mg/kg to induce abstinence for 30 mins to examine the addiction of rats. They were then continued to be treated with heroin for another 10 days, 20 days, 30 days, and 40 days respectively to establish heroin-addicted models. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was employed to identify apoptotic cells [6]. Immunohistochemistry and Western blot assay were also used in the study to examine the protein expressions of c-jun, cytc and Bax in the cerebellum. RESULTS: Compared with the control group, the proportion of apoptotic neurons increased significantly in the heroin addiction groups (10 d, 20 d, 30 d, 40 d) (P < 0.05), also accompanied by markedly increased expressions of c-jun, cytc and Bax (P < 0.05) depending on doses of heroin in the cerebellum. Thus, the significant differences were observed in heroin addiction groups (10 d, 20 d,30 d, 40 d) and control group (P < 0.05). CONCLUSION: Long-term use of heroin may induce neuronal apoptosis in the cerebellum by raising the expressions of pro-apoptotic c-jun, cytc and Bax, which might be one of mechanisms underlying the heroin-induced cerebellum neuronal damage. FAU - Pu, Hongwei AU - Pu H AD - Department of Science and Research Education Center, First Affiliated Hospital of Xinjiang Medical University Urumqi, China. FAU - Wang, Xuemei AU - Wang X AD - Xinjiang Key Laboratory of Medical animal Model Research, First Affiliated Hospital of Xinjiang Medical University Urumqi, China. FAU - Zhang, Jianlong AU - Zhang J AD - College of Basic Medicine, Xinjiang Medical University Urumqi, China. FAU - Ma, Chuang AU - Ma C AD - Department of Micro-Reconstructive Surgery of Orthopedics Center, First Affiliated Hospital of Xinjiang Medical University Urumqi, China. FAU - Su, Yinxia AU - Su Y AD - Clinical Research Institute of The First Affiliated Hospital of Xinjiang Medical University Urumqi, China. FAU - Li, Xiujuan AU - Li X AD - College of Basic Medicine, Xinjiang Medical University Urumqi, China. FAU - Liu, Xiaoshan AU - Liu X AD - Department of Forensic Science, Zhongshan School of Medicine, Sun Yat-Sen University Guangzhou, China. FAU - Su, Liping AU - Su L AD - Department of Pathology, First Affiliated Hospital of Xinjiang Medical University Urumqi, China. LA - eng PT - Journal Article DEP - 20150701 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (BAX protein, human) RN - 0 (Biomarkers) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (bcl-2-Associated X Protein) RN - 9007-43-6 (Cytochromes c) SB - IM MH - Animals MH - *Apoptosis MH - Biomarkers/metabolism MH - Blotting, Western MH - Cerebellum/metabolism/*pathology MH - Cytochromes c/metabolism MH - Disease Models, Animal MH - Heroin Dependence/metabolism/*pathology MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Male MH - Neurons/metabolism/*pathology MH - Proto-Oncogene Proteins c-jun/metabolism MH - Rats, Sprague-Dawley MH - Time Factors MH - bcl-2-Associated X Protein/metabolism PMC - PMC4555723 OTO - NOTNLM OT - Bax OT - Heroin addiction OT - apoptosis OT - c-jun OT - cerebellum OT - cytc EDAT- 2015/09/05 06:00 MHDA- 2016/06/09 06:00 PMCR- 2015/07/01 CRDT- 2015/09/05 06:00 PHST- 2015/05/06 00:00 [received] PHST- 2015/06/23 00:00 [accepted] PHST- 2015/09/05 06:00 [entrez] PHST- 2015/09/05 06:00 [pubmed] PHST- 2016/06/09 06:00 [medline] PHST- 2015/07/01 00:00 [pmc-release] PST - epublish SO - Int J Clin Exp Pathol. 2015 Jul 1;8(7):8260-7. eCollection 2015.