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Neuronal loss in the caudal intralaminar thalamic nuclei in a primate model of Parkinson’s disease

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Abstract

In light of postmortem human studies showing extensive degeneration of the center median (CM) and parafascicular (Pf) thalamic nuclei in Parkinson’s disease patients, the present study assessed the extent of neuronal loss in CM/Pf of non-human primates that were rendered parkinsonian by repeated injections of low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In order to determine the course of CM/Pf degeneration during the MPTP intoxication, motor-asymptomatic animals with partial striatal dopamine denervation were also used. The Cavalieri’s principle for volume estimation and the unbiased stereological cell count method with the optical dissector technique were used to estimate the total number of neurons in the CM/Pf. We found substantial neurons loss in the CM/Pf in both, motor-symptomatic MPTP-treated monkeys in which the striatal dopamine innervation was reduced by more than 80 %, and in motor-asymptomatic MPTP-treated animals with 40–50 % striatal dopamine loss. In MPTP-treated parkinsonian monkeys, 60 and 62 % neurons loss was found in CM and Pf, respectively, while partially dopamine-depleted asymptomatic animals displayed 59 and 52 % neurons loss in the CM and Pf, respectively. Thus, our study demonstrates that the CM/Pf neurons loss is an early phenomenon that occurs prior to the development of parkinsonian motor symptoms in these animals. In contrast, the neighboring mediodorsal nucleus of the thalamus was only mildly affected (18 % neurons loss) in the parkinsonian monkeys. Together with recent findings about the possible role of the CM/Pf-striatal system in cognition, our findings suggest that the pathology of the thalamostriatal system may precede the development of motor symptoms in PD, and may account for some of the cognitive deficits in attentional set-shifting often seen in these patients. Future studies in this animal model, and in monkeys with selective lesion of CM or Pf, are needed to further elucidate the role of the CM/Pf-striatal system in normal and parkinsonian conditions.

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Abbreviations

AchE:

Acetylcholinesterase

Cb:

Calbindin

CD:

Caudate nucleus

CM:

Center median nucleus

MD:

Mediodorsal nucleus

MPP+ :

1-Methyl-4-phenylpyridinium ion

MPTP:

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

PD:

Parkinson’s disease

Pf:

Parafascicular nucleus

Pu:

Putamen

ROI:

Regions of interest

SN:

Substantia nigra

TH:

Tyrosine hydroxylase

vGluT2:

Vesicular glutamate transporter type 2

6-OHDA:

6-Hydroxydopamine

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Acknowledgments

The authors thank Jean-Francois Pare and Susan Jenkins for technical assistance. Thanks are also due to Dr. Gunasingh Masilamoni and the Yerkes Center Animal Resources Division for the MPTP-treatment and care of the monkeys. The authors also thank to Dr. Adriana Galvan for critical reading of the manuscript. Special thanks are due to Professor Carlos Avendaño (Anatomy Department of the School of Medicine, University Autonoma in Madrid, Spain) for his generous help with the initial design of stereological analysis. This work was supported by research grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke Grants R01NS062876 and P50-NS071669 (TW), and by funding from the National Center for Research Resources P51RR000165 and the Office of Research Infrastructure Programs/OD P51OD011132 to the Yerkes National Primate Research Center.

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Authors and Affiliations

  1. Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA, 30329, USA

    R. M. Villalba, T. Wichmann & Y. Smith

  2. Department of Neurology, Emory University, Atlanta, GA, USA

    T. Wichmann & Y. Smith

  3. Udall Center of Excellence for Parkinson’s Disease Research, Emory University, Atlanta, GA, USA

    R. M. Villalba, T. Wichmann & Y. Smith

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  1. R. M. Villalba
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Correspondence to R. M. Villalba.

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Villalba, R.M., Wichmann, T. & Smith, Y. Neuronal loss in the caudal intralaminar thalamic nuclei in a primate model of Parkinson’s disease. Brain Struct Funct 219, 381–394 (2014). https://doi.org/10.1007/s00429-013-0507-9

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