RT Journal Article
SR Electronic
T1 Mice with Partial Deficiency of c-Jun Show Attenuation of Methamphetamine-Induced Neuronal Apoptosis
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 993
OP 1000
DO 10.1124/mol.62.5.993
VO 62
IS 5
A1 Xiaolin Deng
A1 Subramaniam Jayanthi
A1 Bruce Ladenheim
A1 Irina N. Krasnova
A1 Jean Lud Cadet
YR 2002
UL http://molpharm.aspetjournals.org/content/62/5/993.abstract
AB The regional distribution of c-Jun expression and of the number of apoptotic cells was compared in various brain areas after methamphetamine administration to mice. Our results showed that there was methamphetamine-induced overexpression of c-Jun in the cortex and striatum but not in the cerebellar cortex. There was an almost totally similar regional appearance of methamphetamine-induced apoptotic cells in the mouse brain; no apoptosis was present in the cerebellum. Additionally, in the neocortical area, more positive signals for c-Jun immunoreactivity were observed in the piriform cortex, an area that also showed more positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) signals than the frontal and parietal cortices. These observations suggested that c-Jun might be involved in methamphetamine-induced apoptosis. This idea was confirmed by using heterozygous c-Jun knockout mice that showed much less apoptosis than wild-type controls. In addition, we found that the majority of TUNEL-positive cells were also positive for c-Jun–like immunoreactivity in both genotypes. Moreover, methamphetamine-induced caspase-3 activity and PARP cleavage were also reduced in c-Jun heterozygous knockout mice. In contrast, methamphetamine-induced hyperthermia was essentially identical in the two genotypes. When taken together, our data support the hypothesis that c-Jun is involved in methamphetamine-induced apoptosis.