Longitudinal follow-up study of adenoviral vector-mediated gene transfer of dopamine D2 receptors in the striatum in young, middle-aged, and aged rats: a positron emission tomography study.
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.
Umegaki
H
H
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya, Aichi 466-8550, Japan. umegaki@med.nagoya-u.ac.jp
Ishiwata
K
K
Ogawa
O
O
Ingram
D K
DK
Roth
G S
GS
Oda
K
K
Kurotani
S
S
Kawamura
K
K
Wang
W F
WF
Ikari
H
H
Senda
M
M
Iguchi
A
A
D000256:Adenoviridae / Q000235:genetics; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000821:virology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D020891:Raclopride / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D002247:Carbon Isotopes; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D020891:Raclopride