Cerebellar neuronal apoptosis in heroin-addicted rats and its molecular mechanism.
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.


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).


CONCLUSIONS
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.
Department of Science and Research Education Center, First Affiliated Hospital of Xinjiang Medical University Urumqi, China.
Hongwei
H
Pu
Xinjiang Key Laboratory of Medical animal Model Research, First Affiliated Hospital of Xinjiang Medical University Urumqi, China.
Xuemei
X
Wang
College of Basic Medicine, Xinjiang Medical University Urumqi, China.
Jianlong
J
Zhang
Department of Micro-Reconstructive Surgery of Orthopedics Center, First Affiliated Hospital of Xinjiang Medical University Urumqi, China.
Chuang
C
Ma
Clinical Research Institute of The First Affiliated Hospital of Xinjiang Medical University Urumqi, China.
Yinxia
Y
Su
College of Basic Medicine, Xinjiang Medical University Urumqi, China.
Xiujuan
X
Li
Department of Forensic Science, Zhongshan School of Medicine, Sun Yat-Sen University Guangzhou, China.
Xiaoshan
X
Liu
Department of Pathology, First Affiliated Hospital of Xinjiang Medical University Urumqi, China.
Liping
L
Su
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D006556:Heroin Dependence / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D015415:Biomarkers; D016755:Proto-Oncogene Proteins c-jun; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c
Bax; Heroin addiction; apoptosis; c-jun; cerebellum; cytc