TitleThree-dimensional and stereological characterization of the human substantia nigra during aging.
Publication TypeJournal Article
Year of Publication2016
AuthorsAlho ATereza Di, Suemoto CKimie, Polichiso L, Tampellini E, de Oliveira KCristina, Molina M, Santos GAparecida, Nascimento C, Leite RElaine Par, Ferreti-Rebustini REloah de L, da Silva AValotta, Nitrini R, Pasqualucci CAugusto, Jacob-Filho W, Heinsen H, Grinberg LTenenholz
JournalBrain Struct Funct
Date Published2016 09
KeywordsAged, Aged, 80 and over, Aging, Cell Count, Female, Humans, Imaging, Three-Dimensional, Male, Middle Aged, Neurons, Substantia Nigra

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.

Alternate JournalBrain Struct Funct
PubMed ID26386691
PubMed Central IDPMC4799775
Grant ListR01 AG040311 / AG / NIA NIH HHS / United States