Anatomy and Embryology

, Volume 210, Issue 2, pp 101–123 | Cite as

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

  • Emily Fitzpatrick
  • Keyoumars Ashkan
  • Bradley A. Wallace
  • Alim-Louis Benabid
  • John Mitrofanis
Original Article

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.

Keywords

Calbindin Tyrosine hydroxylase MPTP Parkinson disease 6OHDA 

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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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Emily Fitzpatrick
    • 1
  • Keyoumars Ashkan
    • 2
    • 3
  • Bradley A. Wallace
    • 2
    • 4
  • Alim-Louis Benabid
    • 2
  • John Mitrofanis
    • 1
    • 2
    • 5
  1. 1.Department of Anatomy & HistologyUniversity of Sydney Australia
  2. 2.Department of Clinical NeurosciencesUniversity of Joseph FourierGrenobleFrance
  3. 3.Functional Neurosurgery UnitInstitute of NeurologyLondonUK
  4. 4.Department of NeurosurgeryUniversity of FloridaGainesvilleUSA
  5. 5.Australian National University, Medical SchoolCanberraAustralia

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