Selective loss of subpopulations of ventral mesencephalic dopaminergic neurons in the monkey following exposure to MPTP

1987 ◽  
Vol 411 (1) ◽  
pp. 144-150 ◽  
Author(s):  
J.S. Schneider ◽  
A. Yuwiler ◽  
C.H. Markham
Keyword(s):  
Dopaminergic Neurons ◽  
Selective Loss ◽  
Ventral Mesencephalic

scholarly journals Intrastriatal Ventral Mesencephalic Xenografts of Porcine Tissue in Rats: Immune Responses and Functional Effects

2000 ◽  
Vol 9 (2) ◽  
pp. 261-272 ◽  
Author(s):  
Lena C. Larsson ◽  
Kimberly A. Czech ◽  
Patrik Brundin ◽  
Håkan Widner
Keyword(s):  
Immune Responses ◽  
Graft Survival ◽  
Functional Recovery ◽  
Dopaminergic Neurons ◽  
Immunosuppressive Treatment ◽  
Neural Tissue ◽  
Scar Tissue ◽  
Rat Striatum ◽  
Intracerebral Transplantation ◽  
Ventral Mesencephalic

Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested for amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750 ± 1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (n = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.

scholarly journals A Drosophila Model of Mutant Human Parkin-Induced Toxicity Demonstrates Selective Loss of Dopaminergic Neurons and Dependence on Cellular Dopamine

2007 ◽  
Vol 27 (5) ◽  
pp. 981-992 ◽  
Author(s):  
T.-K. Sang ◽  
H.-Y. Chang ◽  
G. M. Lawless ◽  
A. Ratnaparkhi ◽  
L. Mee ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Selective Loss ◽  
Drosophila Model

Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue

Neuroscience ◽  
2005 ◽  
Vol 133 (3) ◽  
pp. 701-713 ◽  
Author(s):  
R.H. Andres ◽  
A.W. Huber ◽  
U. Schlattner ◽  
A. Pérez-Bouza ◽  
S.H. Krebs ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Ventral Mesencephalic

The Age of Striatum Determines the Pattern and Extent of Dopaminergic Innervation: a Nigrostriatal Double Graft Study

1997 ◽  
Vol 6 (3) ◽  
pp. 287-296 ◽  
Author(s):  
Ingrid Stromberg ◽  
Lars Björklund ◽  
Petter Forander
Keyword(s):  
Nerve Fiber ◽  
Growth Pattern ◽  
Dopaminergic Neurons ◽  
Nerve Fibers ◽  
Growth Patterns ◽  
Ganglionic Eminence ◽  
Fiber Network ◽  
Lateral Ganglionic Eminence ◽  
Ventral Mesencephalic ◽  
Dopaminergic Grafts

In animal models of Parkinson's disease, transplanted fetal mesencephalic dopaminergic neurons can innervate the dopamine-depleted host brain, but it is unclear why large portions of the host striatum are left uninnervated. During normal development, the dopaminergic innervation first occurs in the form of a dense patchy pattern in the striatum, followed by a widespread nerve fiber network. Using intraocular double grafts we have investigated dopaminergic growth patterns initiated when ventral mesencephalic grafts innervate striatal targets. The fetal lateral ganglionic eminence was implanted into the anterior eye chamber. After maturation in oculo, fetal ventral mesencephalon was implanted and placed in contact with the first graft. In other animals the two pieces of tissue were implanted simultaneously. Tyrosine hydroxylase (TH) immunohistochemistry revealed a pattern of dense TH-positive patches throughout the total volume of the striatal grafts in simultaneously transplanted cografts, while a widespread, less dense, pattern was found when mature striatal transplants were innervated by fetal dopaminergic grafts. To investigate which type or types of growth patterns that developed after grafting to striatum in situ of an adult host, fetal ventral mesencephalic tissue was implanted into the lateral ventricle adjacent to the dopamine-lesioned striatum. After maturation of the mesencephalic graft, the fetal lateral ganglionic eminence was implanted into the reinnervated part of the host striatum. TH immunohistochemistry revealed a few nerve fibers within the striatal graft and the growth pattern was of the widespread type. In conclusion, grafted dopaminergic neurons preferably innervate mature striatum with a widespread sparse nerve fiber network, while the innervation of the immature striatum occurs in the form of dense patches. Furthermore, when the patchy pattern is formed, the total volume of the striatal target is innervated while growth of the widespread type terminates prior to reaching distal striatal parts. Thus, the growth pattern seems essential to the final volume that is innervated. Once the widespread growth pattern is initiated, the presence of immature striatum does not change the dopaminergic growth pattern.

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