| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
BACKGROUND: The nucleus tractus solitarii (NTS) is known to be the principal termination site of the primary afferent fibers from peripheral barorecepters. It has been reported that bilateral microinjection of an antisense neuronal nitric oxide synthase (nNOS). oligonucleotide into the NTS increases in arterial blood pressure (ABP). In the previous study, we demonstrated that direct in vivo protein transduction into a specific restricted brain area is possible in rats by microinjecting β-galactosidase (β-gal) with hemagglutinnating virus of Japan envelope (HVJ-E) vector. However, it is not known whether the transducted protein fulfills its function. In the present study, we examined the effect of direct in vivo nNOS protein transduction into the NTS on circulation.
METHODS: Male Wistar rats, weighing 250-350 g, were anesthetized with urethane (1.45 g/kg, i.p.). The ABP, mean ABP (mABP), and heart rate (HR) was measured continuously. The nNOS with HVJ-E vector was microinjected bilateral
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ly into the NTS. As a control β-gal protein with HVJ-E vector was microinjected similarly. After the experiment, the medulla oblongata was removed and the immunohistochemical staining was performed.
RESULTS: Microinjection of nNOS with HVJ-E vector into the NTS produced a significant decrease in mABP compared with the control at 1h - 3h. (1h: nNOS, 94% of the value at Oh, n=6; 3 -gal, 106%, n=9; p<0.05. 2h: nNOS, 89%; /3 -gal, 106%, n=9; p<0.01. 3h: nNOS, 86%; 3 -gal, 106%, n=9; p<0.01.)
RESULTS: Microinjection of nNOS with HVJ-E vector into the NTS produced a significant decrease in mABP compared with the control at 1h - 3h. (1h: nNOS, 94% of the value at Oh, n=6; 3 -gal, 106%, n=9; p<0.05. 2h: nNOS, 89%; /3 -gal, 106%, n=9; p<0.01. 3h: nNOS, 86%; 3 -gal, 106%, n=9; p<0.01.)
RESULTS : Microinjection of nNOS with HVJ-E vector into the NTS produced a significant decrease in mABP compared with the control at lh - 3h. (1h:nNOS, 94% of the value at Oh, n=6 ; 3 -gal, 106%, n=9 ; p<0.05. 2h:nNOS, 89% ; /3 -gal, 106%, n=9 ; p<0.01. 3h:nNOS, 86% ; 3 -gal, 106%, n=9 ; p<0.01.)
CONCLUSION : We demonstrated here that the transducted protein fulfills its function. We suggested that the type of targeted delivery system we present here may have wide applications in the administration of therapeutic proteins to the central nervous system. Less
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