[Responsive changes to MPTP in rats with DAT inhibited by antisense oligonucleotides].
OBJECTIVE
To investigate the inhibitory effect of antisense oligonucleotides (ODN) on dopamine transporter (DAT) in rats and observe the response of the rats to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).


METHODS
The cannula was implanted in the substantia nigra compacta under a rat stereotaxic device, through which drugs were used. The rats with successful operation were divided randomly into four groups, and received injection of antisense, sense, missense oligonucleotides and saline respectively, in the substantia nigra compacta of each rat via the cannula, followed by MPTP (30 mg/kg) injection. Behavior of the rats was observed and immunohistochemistry was carried out to check the expression of DAT and apoptosis of dopamine cell.


RESULTS
The expression of DAT (positive unit, PU) in the substantia nigra compacta in rats was 6.65+/- 1.67 in the antisense ODN group, 12.41+/- 2.46 in saline group, 11.45+/- 1.17 in sense ODN group, and 10.35+/- 2.89 in missense ODN group. The expression of DAT was lower in the antisense ODN group than that of the other three groups (P< 0.01). The rotation of the rats induced by apomorphine was slower than that of the other three groups(P< 0.05). The apoptotic cells (21.4+/- 5.6) in the antisense ODN group (200x ) were less than that of the other three groups (61.6+/- 19.7, 56.5+/- 16.3, 52.2+/- 12.5 respectively), (P< 0.01).


CONCLUSIONS
The expression of DAT can be inhibited effectively by the antisense ODN, and the response of the rats to the MPTP was reduced upon DAT inhibition.
Xu
Yan-ming
YM
Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 P. R. China. neuroxym@163.net
Tao
En-xiang
EX
Ding
Xiao-jun
XJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D050483:Dopamine Plasma Membrane Transport Proteins; D016376:Oligonucleotides, Antisense; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine