Assessment of Dopaminergic Neurodegeneration in Mice

Abstract

Neuron death is a key feature of neurological disorders like Alzheimer's or Parkinson's disease (PD). As a result, analysis of neurodegeneration is often considered a central experiment in the postmortem characterization of preclinical PD animal models. Stereology provides a precise estimate of particles, like neurons, in three-dimensional objects, like the brain, and is the gold standard quantification approach for the assessment of neuron survival in neurodegenerative disease research. Here, we provide a detailed step-by-step guide for the quantification of dopaminergic neurons in the substantia nigra pars compacta, a brain area prone to neuron loss in PD. In addition, we outline the protocol for the analysis of the dopaminergic terminals in the striatum, the projection area of midbrain dopaminergic neurons, as a readout for the integrity of the nigrostriatal projections.

Keywords: Immunohistochemistry; Mouse models; Neurodegeneration; Optical densitometry; Optical fractionator; Parkinson’s disease; Physical fractionator; Stereology; Striatum; Substantia nigra pars compacta.