A protocol for concurrent high-quality immunohistochemical and biochemical analyses in adult mouse central nervous system

Eur J Neurosci. 2014 Jan;39(2):165-75. doi: 10.1111/ejn.12447. Epub 2013 Dec 10.

Abstract

Biochemical analysis of central nervous system proteins and nucleic acids requires fresh-tissue homogenates, whereas immunohistochemistry usually is performed in sections prepared from perfusion-fixed tissue. Post-mortem immersion-fixation is possible, but largely impairs morphological preservation and protein antigenicity. Here, we present a simple, fast and versatile protocol allowing concurrent biochemical and immunohistochemical analysis, including pre-embedding immunoelectron microscopy, using tissue from the same animal. The protocol includes a brief transcardiac perfusion with ice-cold, oxygenated and glucose-supplemented artificial cerebrospinal fluid to maintain brain tissue alive, prior to isolation of regions of interest, followed by homogenisation for biochemistry or immersion-fixation for immunohistochemistry. We provide several examples demonstrating that this protocol allows optimal biochemical and morphological analysis, characterised with optimal sensitivity and preservation of tissue structure, along with a reduction of artefacts typically seen in perfusion-fixed tissue. This protocol should find widespread applications for combining analytical methods in tissue from the same animal, thereby reducing the number of mice required for a given experiment.

Keywords: RT-PCR; Western blot; antibodies; immunofluorescence; ultrastructure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / metabolism
  • Brain / ultrastructure*
  • Brain Chemistry*
  • Cell Adhesion Molecules, Neuronal / analysis
  • Extracellular Matrix Proteins / analysis
  • Gene Expression Profiling / methods
  • Glutamate Decarboxylase / genetics
  • Green Fluorescent Proteins / genetics
  • Immunohistochemistry / methods*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Immunoelectron / methods
  • Nerve Tissue Proteins / analysis
  • Neurons / chemistry
  • Neurons / cytology
  • Perfusion
  • Real-Time Polymerase Chain Reaction
  • Receptors, GABA-A / analysis
  • Reelin Protein
  • Serine Endopeptidases / analysis
  • Subcellular Fractions / chemistry
  • Tissue Preservation

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • Reelin Protein
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Serine Endopeptidases
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1