Resumen de Three-dimensional and stereological characterization of the human substantia nigra during aging.

Ana Tereza Di Lorenzo Alho, Claudia Kimie Suemoto, Lívia Polichiso, Edilaine Tampellini, Kátia Cristina de Oliveira, Mariana Molina, Glaucia Aparecida Bento Santos, Camila Nascimento, Renata Elaine Paraizo Leite, Renata Eloah de Lucena Ferreti-Rebustini, Alexandre Valotta da Silva, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob-Filho, Helmut Heinsen, Lea Tenenholz Grinberg

• The human brain undergoes non-uniform changes during aging. The substantia nigra (SN), the source of major dopaminergic pathways in the brain, is particularly vulnerable to changes in the progression of several age-related neurodegenerative diseases. To establish normative data for high-resolution imaging, and to further clinical and anatomical studies we analyzed SNs from 15 subjects aged 50-91 cognitively normal human subjects without signs of parkinsonism. Complete brains or brainstems with substantia nigra were formalin-fixed, celloidin-mounted, serially cut and Nissl-stained. The shapes of all SNs investigated were reconstructed using fast, high-resolution computer-assisted 3D reconstruction software. We found a negative correlation between age and SN volume (p = 0.04, rho = -0.53), with great variability in neuronal numbers and density across participants. The 3D reconstructions revealed SN inter- and intra-individual variability. Furthermore, we observed that human SN is a neuronal reticulum, rather than a group of isolated neuronal islands. Caution is required when using SN volume as a surrogate for SN status in individual subjects. The use of multimodal sequences including those for fiber tracts may enhance the value of imaging as a diagnostic tool to assess SN in vivo. Further studies with a larger sample size are needed for understanding the structure-function interaction of human SN.;