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Neurostereology

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Front. Neuroanat. | doi: 10.3389/fnana.2017.00109

Application of the physical disector principle for quantification of dopaminergic neuronal loss in a rat 6-hydroxydopamine nigral lesion model of Parkinson's disease

 Katrine Fabricius1*, Pernille Barkholt2,  Jacob Jelsing2 and Henrik H. Hansen1
  • 1Pharmacology research, Gubra, Denmark
  • 2Histology, Gubra, Denmark

Stereological analysis is the optimal tool for quantitative assessment of brain morphological and cellular changes induced by neurotoxic lesions or treatment interventions. Stereological methods based on random sampling techniques yield unbiased estimates of particle counts within a defined volume, thereby providing a true quantitative estimate of the target cell population. Neurodegenerative diseases involve loss of specific neuron types, such as the midbrain tyrosine hydroxylase-positive dopamine neurons in Parkinson’s disease and in animal models of nigrostriatal degeneration. Therefore, we applied an established automated physical disector principle in a fractionator design for efficient stereological quantitative analysis of tyrosine hydroxylase (TH)-positive dopamine neurons in the substantia nigra pars compacta of hemiparkinsonian rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. We obtained reliable estimates of dopamine neuron numbers, and established the relationship between behavioral asymmetry and dopamine neuron loss on the lesioned side. In conclusion, the automated physical disector principle provided a useful and efficient tool for unbiased estimation of TH-positive neurons in rat midbrain, and should prove valuable for investigating neuroprotective strategies in 6-OHDA model of parkinsonism, while generalizing to other immunohistochemically-defined cell populations.
Abbreviations:
6-OHDA, 6-hydroxydopamine; asf, area sampling fraction; DA, dopaminergic; hsf, height sampling fraction; i.p., intraperitoneal; MFB, medial forebrain bundle; PD, Parkinson’s disease; ROI, region of interest; s.c., subcutaneous; SEM, standard error of the mean; SNc, substantia nigra pars compacta; SPD, Sprague-Dawley; ssf, section sampling fraction; SURS, systematic uniform random sampling; TBS, Tris-buffered saline; TH, tyrosine hydroxylase.

Keywords: Physical disector, Autodisector, Stereology, 6-OHDA rat model, Substantia Nigra, Parkinson Disease

Received: 01 Aug 2017; Accepted: 06 Nov 2017.

Edited by:

Sanne S. Kaalund, Research Laboratory for Stereology and Neuroscience, Denmark

Reviewed by:

Miguel Angel García-Cabezas, Boston University, United States
Hans J. Gundersen, Retired, Denmark  

Copyright: © 2017 Fabricius, Barkholt, Jelsing and Hansen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Katrine Fabricius, Gubra, Pharmacology research, Hørsholm Kongevej 11B, Hørsholm, 2970, Denmark, katrinefabricius@hotmail.com