Umegaki H, Ishiwata K, Ogawa O, Ingram D K, Roth G S, Oda K, Kurotani S, Kawamura K, Wang W F, Ikari H, Senda M, Iguchi A
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya, Aichi 466-8550, Japan.
Neuroscience. 2003;121(2):479-86. doi: 10.1016/s0306-4522(03)00489-5.
Overexpression of dopamine D(2) receptors by adenoviral vector-mediated gene transfer in the rat striatum was evaluated by positron emission tomography in vivo and by ex vivo autoradiography in 5-, 13-, and 24-month-old Fischer 344 rats. Each rat had hemilateral gene transfer of D(2) receptors mediated by adenoviral vectors (AdCMV.DopD(2)R) in the striatum with contralateral striatal injection of control vectors (AdCMV.LacZ). At day 2 or 3 after vector injection positron emission tomography or ex vivo autoradiography was performed. The binding potential of a radiolabeled D(2) receptors ligand, [11C]raclopride, was significantly higher in the D(2) receptors gene-transferred striatum than the control side in each age group at a similar degree. The binding potential in the AdCMV.DopD(2)R-injected striatum of 24-month-old rats was similar to that in the AdCMV.LacZ-injected striatum of 5-month-old rats (0.99+/-0.14 versus 0.91+/-0.08). A significant age-associated decrease of the binding potential of [11C]raclopride was found in the control vector-injected side, and a significant increase of the binding potential in the adenoviral vector-injected side in all three age groups, suggesting no aging effect on the overexpression of D(2) receptors. A group of rats underwent follow-up assessment by positron emission tomography. The overexpression of D(2) receptors decreased with time in all three groups; however, the decrease rate of the D(2) receptors expression was significantly smaller in the 24-month-old group than in the 5-month-old group. We confirmed that the adenoviral vector-mediated gene transfer of D(2) receptors compensated the decreased density of striatal D(2) receptors in the 24-month-old rats up to the level in the control striatum of 5-month-old rats, and the decrease rate of the overexpression was significantly smaller in aged rats.
通过腺病毒载体介导的基因转移使大鼠纹状体中多巴胺D(2)受体过表达，采用正电子发射断层扫描术在体评估以及对5月龄、13月龄和24月龄的Fischer 344大鼠进行离体放射自显影评估。每只大鼠在纹状体中接受腺病毒载体（AdCMV.DopD(2)R）介导的D(2)受体单侧基因转移，对侧纹状体注射对照载体（AdCMV.LacZ）。在载体注射后第2天或第3天进行正电子发射断层扫描或离体放射自显影。在各年龄组中，放射性标记的D(2)受体配体[11C]雷氯必利的结合潜能在D(2)受体基因转移的纹状体中均显著高于对照侧，且程度相似。24月龄大鼠注射AdCMV.DopD(2)R的纹状体中的结合潜能与5月龄大鼠注射AdCMV.LacZ的纹状体中的结合潜能相似（0.99±0.14对0.91±0.08）。在注射对照载体的一侧发现[11C]雷氯必利的结合潜能随年龄显著降低，而在所有三个年龄组中，注射腺病毒载体的一侧结合潜能显著增加，提示衰老对D(2)受体过表达无影响。一组大鼠通过正电子发射断层扫描进行随访评估。所有三个组中D(2)受体的过表达均随时间降低；然而，24月龄组中D(2)受体表达的降低速率显著小于5月龄组。我们证实，腺病毒载体介导的D(2)受体基因转移可将24月龄大鼠纹状体中D(2)受体密度的降低补偿至5月龄大鼠对照纹状体的水平，且老年大鼠中过表达的降低速率显著较小。
