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Differential survival patterns among midbrain dopaminergic cells of MPTP-treated monkeys and 6OHDA-lesioned rats

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Abstract

We explore the patterns of survival among dopaminergic cells of the midbrain in MPTP-treated macaque monkeys and 6OHDA-lesioned Sprague-Dawley rats. For the monkeys, animals were injected intramuscularly with MPTP for 8 days consecutively and then allowed to survive for 21 days. For the rats, 6OHDA was injected into the midbrain and then allowed to survive for either 7, 28 or 84 days. Brains were processed for tyrosine hydroxylase (TH) and calbindin immunocytochemistry to label populations in the ventral and dorsal tiers of midbrain dopaminergic cells. In monkeys, while there was a decrease in the TH+ cell number in the ventral tier of MPTP-treated cases (65%), there was an overall increase (22%) in the TH+ and calbindin+ cell number in the dorsal tier. Double labelling studies indicate that ∼50% of TH+ cells of the dorsal tier contain calbindin also. In rats, there was a decrease in TH+ cell number in the ventral tier of 6OHDA-lesioned cases (97%), and to a lesser extent, in the TH+ and calbindin+ cell number in the dorsal tier (∼40%). In conclusion, we show a surprising increase in TH+ and calbindin+ cell number in the dorsal tier in response to MPTP insult; such an increase was not evident after 6OHDA insult. We suggest that the increase in antigen expression relates to the dopaminergic reinnervation of the striatum in MPTP-treated cases. We also suggest that the greater loss of dopaminergic cells in the ventral tier when compared to the dorsal tier relates to glutamate toxicity.

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Abbreviations

6OHDA:

6 hydroxydopamine

ABC:

Avidin biotin peroxidase complex

Cb:

Calbindin D28 k

DAB:

3,3-diaminobenzidine

dSNc:

Dorsal substantia nigra pars compacta

GABA:

γaminobutyric acid

III:

Oculomotor nerve

LG:

Lateral geniculate nucleus

MG:

Medial geniculate nucleus

Ml:

Medial lemniscus

MPTP:

Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PBS:

Phosphate-buffered saline

R:

Red nucleus

RrF:

Retrorubral field

SC:

Superior colliculus

SNc:

Substantia nigra pars compacta

SNr:

Substantia nigra pars reticulata

Sub:

Subthalamus

TH:

Tyrosine hydroxylase

VL:

Ventral lateral nucleus of thalamus

VP:

Ventral posterior nucleus of thalamus

vSNc:

Ventral substantia nigra pars compacta

VTA:

Ventral tegmental area

ZI:

Zona incerta

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Acknowledgements

We thank Medtronic and Tenix corp/Salteri family for their most generous funding of this work. Laurance Grotti and Sharon Spana provided invaluable technical assistance with the immunostaining and histology, while Rolande Gerbex and Louis Gonzales provided excellent assistance looking after the animal house.

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Correspondence to John Mitrofanis.

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Fitzpatrick, E., Ashkan, K., Wallace, B.A. et al. Differential survival patterns among midbrain dopaminergic cells of MPTP-treated monkeys and 6OHDA-lesioned rats. Anat Embryol 210, 101–123 (2005). https://doi.org/10.1007/s00429-005-0003-y

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Keywords

  • Calbindin
  • Tyrosine hydroxylase
  • MPTP
  • Parkinson disease
  • 6OHDA