Article Figures & Data
Figures
- Fig. 1.
Long-term functional recovery of CB-grafted hemiparkinsonian rats. A, Evolution of the rotational behavior in CB-grafted animals measured before the transplantation (BT) or at the end of the period they were allowed to survive (between 5 and 15 months) (AT). Animals' behavior was evaluated by the amphetamine (left ordinate) and apomorphine (right ordinate) tests. Animals were classified in groups I and II depending on the behavioral and histological characteristics (see Results). Apomorphine tests were done only on animals that had some functional recovery in the amphetamine test to detect upregulation of dopamine receptors. Behavioral status is as follows (mean ± SEM in turns per hour): group I, amphetamine test, BT = 787 ± 171 (n = 6) and AT = 138 ± 53 (n = 6); apomorphine test, AT = 3 ± 5 (n = 5); group II, amphetamine test, BT = 1206 ± 145 (n = 6) and AT = 872 ± 179 (n = 6); apomorphine test, AT = 328 ± 133 (n = 3). B, Same analysis as in A performed in the group of sham-operated animals that rotated <900 turns per hour. Behavioral status is as follows (mean ± SEM in turns per hour): amphetamine test, BT = 671 ± 54 (n = 8) and AT = 702 ± 159 (n = 8); apomorphine test, AT = 298 ± 27 (n = 3). *p < 0.02, statistically significant with respect to BT in the same group (t test); **p < 0.02, statistically significant with respect to the same test in group II and in B(t test).
- Fig. 2.
Long-term striatal reinnervation and survival of substantia nigra neurons in carotid body-grafted rats.A–D, Striatal dopaminergic reinnervation in a representative animal of group I killed 5.5 months after carotid body transplantation (AT). BT, Before transplantation. Normal (A) and reinnervated (B) striata are shown for comparison.Insets at high magnification show the appearance of TH-positive striatal fibers. The region with the carotid body graft (g) is shown in C andD at higher magnifications. Note the numerous typical glomus cells in the graft arranged in glomeruli. E, Localization of FG injection in the striatum near the graft.F, Retrograde labeling of numerous cells in the ipsilateral substantia nigra. Midline is indicated by the dotted line. A–E, Transmitted light and immunostaining with antibody against TH. E, F, UV illumination. Behavioral parameters of this animal (turns per hour) were as follows: amphetamine test, BT = 1512 and AT = 111; apomorphine test, AT = −9. Striatal reinnervation, 70.7%.
- Fig. 3.
Lack of striatal reinnervation in carotid body-grafted animals with complete destruction of substantia nigra neurons. Comparison of the normal (A) and denervated (B) striata in a representative animal of group II killed 5 months after carotid body transplantation (AT). Insets at high magnification show the appearance of TH-positive striatal fibers. Localization of the graft (g) is shown in C and inD and E at higher magnification. Note the large size of the graft with abundant glomus cells. Appearance of the normal (F, H) and lesioned (G, I) substantia nigra in the same animal. Note the complete absence of dopaminergic cells in the lesioned substantia nigra and the marked reduction of stained cells in the ventral tegmental area. Arrowheads inI indicate the track of the needle used for 6-OHDA injection. Immunostaining with antibody against TH (A,B, D, F, G) and TH mRNA in situ hybridization (C,E, H, I). Behavioral parameters of this animal is as follows (turns per hour): amphetamine test, BT = 1293 and AT = 1473. Striatal reinnervation, 2.1%.
- Fig. 4.
Identification and localization of GDNF and the GDNF multicomponent receptor complex in the carotid body.A, RT-PCR showing the existence of GDNF and the high-affinity GDNF receptor complex (GFRα1 and c-ret) in the CB. Note the parallel experiment illustrating the absence of GDNF message in the SCG. TH is also amplified to test for mRNA stability. B, X-gal staining (blue) of histological sections at the level of the carotid artery bifurcation from heterozygous GDNF/lacZ knock-out mice at two magnifications illustrating the dense appearance of GDNF-positive cells in the CB and the complete absence of GDNF expression in the SCG. C, Colocalization of GDNF (blue)- and TH (brown)-positive cells in the same glomeruli. Note that TH immunostaining is absent from glomeruli without GDNF-positive cells (asterisks).D, Example at higher magnification of colocalization of TH and GDNF expression. E–H, Localization of GDNF-positive cells in close apposition with TH-positive cells.F–H, The focus was changed in steps of 4 μm to illustrate how some GDNF-positive cells (indicated byarrowheads) are arranged juxtaposed on a glomus cell.
- Fig. 5.
Differential expression of dopamine transporter in substantia nigra and carotid body cells. A, In situ hybridization in consecutive mesencephalic (SN) and CB slices with probes against DAT and TH mRNAs. DAT message was undetectable in CB slices. B, RT-PCR showing the lack of expression of DAT in the carotid body and comparison with SN. TH mRNA was amplified in parallel to demonstrate mRNA stability. C, TH immunohistochemistry of mesencephalic and carotid body slices from control and MPTP-treated (30 mg/kg daily for 55 d) C57BL/6 mice. Note that systemic administration of MPTP produced a marked destruction of dopaminergic SN neurons but left intact CB glomus cells.
