Modern Stereological Evaluation in the Aging Human Substantia Nigra

Quantitative estimation of neuronal numbers in the human substantia nigra (SN) can be achieved by a conventional single section (SS) count or by the more modern stereological disector (DS) count. However, counting results from SS counts are potentially biased and might not accurately reflect the total neuronal number in the SN or the changes in the total number of neurons occurring during aging or with neurodegenerative disease. Potential sources of bias include the lack of linearity between cell number per area of section and cell number per volume; the variation in the counting level and orientation of tissue sections; and shrinkage of tissue. Modern stereological DS counting overcomes these problems and has played a crucial role in many recent studies in neuropathology, neuroanatomy, neuropharmacology and neurogenetics. Over the past decades, four stereology based counting methods including physical DS, physical fractionator, optical DS and optical fractionator, have been established for quantitative measurement. Recently, stereological estimates have revealed a linear reduction rate of total nigral neuronal numbers with age of about 10% per decade. These findings suggest that the surviving nigral neurons undergo a degenerative change leading to neuronal dysfunction with aging. Furthermore, as an advanced quantitative tool, modern stereological evaluation may provide new insights into the aging of the human SN thereby enabling us to better understand the pathophysiological processes in aging brain.