Stereotaxic Surgical Targeting of the Nonhuman Primate Caudate and Putamen: Gene Therapy for Huntington's Disease

Methods Mol Biol. 2016:1382:409-28. doi: 10.1007/978-1-4939-3271-9_29.

Abstract

Stereotaxic surgery is an invaluable tool to deliver a variety of gene therapy constructs to the nonhuman primate caudate and putamen in preclinical studies for the genetic, neurodegenerative disorder, Huntington's disease (HD). Here we describe in detail how to perform this technique beginning with a pre-surgical magnetic resonance imaging scan to determine surgical coordinates followed by the stereotaxic surgical injection technique. In addition, we include methodology of a full necropsy including brain and peripheral tissue removal and a standard immunohistochemical technique to visualize the injected gene therapy agent.

Keywords: Huntington’s disease; Immunohistochemistry; Magnetic resonance imaging; Necropsy; Neurodegeneration; Nonhuman primate; Stereotaxic surgery.

MeSH terms

  • Animals
  • Caudate Nucleus / metabolism*
  • Disease Models, Animal
  • Genetic Therapy
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / pathology
  • Huntington Disease / therapy*
  • Macaca mulatta
  • Magnetic Resonance Imaging
  • Nerve Tissue Proteins / genetics*
  • Putamen / metabolism*
  • Stereotaxic Techniques

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins