[Apoptosis in adult mouse brain after chronic poisoning of ketamine].
OBJECTIVE
To study the effect of chronic poisoning of ketamine on brain cell apoptosis in adult mouse under different duration and doses.


METHODS
The mouse model of chronic poisoning of ketamine was established on adult mouse by tail vein injection of ketamine twice every week with different doses (4, 10, 20 and 30 mg/kg). The mice were sacrificed after continuous injection of ketamine of 1, 2, 4, 8 and 12 weeks. The qualitative assessment of apoptosis was made by transmission electron microscope and the quantitative assessment was made by Caspase-3 immumofluorescence staining method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to estimate the time point of apoptosis. All the experimental results were statistically analyzed.


RESULTS
The neuron apoptosis was observed in hippocampus and corpus striatum by transmission electron microscope one week after administration, and continued for eight weeks. High level of Caspase-3 expression was observed one week after administration, but with a low level expression after 4 weeks. The number of TUNEL positive cells obviously increased one week after administration and maintained in a high number at 4 weeks.


CONCLUSIONS
Ketamine by tail vein injection could induce neuron apoptosis in adult mouse.
Department of Pathology, the Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China. yangju_33@126.com
Ju
J
Yang
Department of Pathology, the Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
Xiao-jing
XJ
Li
Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, China.
Zhi-xiang
ZX
Zhang
Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, China.
Kai-ming
KM
Lu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D049429:Forensic Pathology / Q000379:methods; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000506:poisoning*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D007649:Ketamine; C505409:Casp3 protein, mouse; D053148:Caspase 3