Comparison of unbiased estimation of neuronal number in the rat hippocampus with different staining methods

J Neurosci Methods. 2015 Oct 30:254:73-9. doi: 10.1016/j.jneumeth.2015.07.022. Epub 2015 Jul 31.

Abstract

Background: NeuN and Nissl staining (toluidine blue, cresyl violet staining) are routinely used methods in unbiased stereological estimation of the total number of hippocampal neurons.

New method: In the present study, we stained serial frozen coronal sections from 5 normal adult male Sprague-Dawley rat brains with different methods, measured the deformation of hippocampal area in brain sections and estimated the total number of hippocampal neurons using the optical fractionator.

Results: The deformation in x, y-axis was not obviously different with different staining protocols, but shrinkage in z-axis was significant after staining (p < 0.001). NeuN staining produced significant higher estimate number than cresyl violet staining by 24% (p = 0.002), however, NeuN and Cresyl Violet staining showed a high degree of correlation in quantification of total neuronal numbers and both methods are suitable for unbiased stereological estimation.

Comparison with existing method (s): NeuN is more reliable but if time is limited or the number of animals used in experiments is high, cresyl violet staining may be a feasible method.

Conclusions: Compared with previous estimates of the neurons number in rat hippocampus, our present data is reliable and the stereological analysis based on our system is a cost-effective unbiased method for estimation of neuron number.

Keywords: Hippocampal neuron; Histological study; Stereological analysis; Unbiased estimation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism
  • Benzoxazines
  • Cell Count / methods*
  • Coloring Agents
  • Feasibility Studies
  • Hippocampus / cytology*
  • Hippocampus / metabolism
  • Imaging, Three-Dimensional / methods
  • Immunohistochemistry / methods
  • Male
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology*
  • Neurons / metabolism
  • Rats, Sprague-Dawley
  • Tolonium Chloride

Substances

  • Antigens, Nuclear
  • Benzoxazines
  • Coloring Agents
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Tolonium Chloride
  • cresyl violet