title: Three-dimensional and stereological characterization of the human substantia nigra during aging.
abstract: 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.
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Labor für Morphologische Hirnforschung der Klinik und Poliklinik für Psychiatrie und Psychotherapie, Institut Rechtsmedizin, Universitätsklinikum Würzburg, Würzburg, Germany.|Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Ana Tereza
authors.initials: AT
authors.lastname: Di Lorenzo Alho
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Discipline of Geriatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Claudia Kimie
authors.initials: CK
authors.lastname: Suemoto
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.
authors.forename: Lívia
authors.initials: L
authors.lastname: Polichiso
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.
authors.forename: Edilaine
authors.initials: E
authors.lastname: Tampellini
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Labor für Morphologische Hirnforschung der Klinik und Poliklinik für Psychiatrie und Psychotherapie, Institut Rechtsmedizin, Universitätsklinikum Würzburg, Würzburg, Germany.
authors.forename: Kátia Cristina
authors.initials: KC
authors.lastname: de Oliveira
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Molina
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Glaucia Aparecida Bento
authors.initials: GA
authors.lastname: Santos
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Nascimento
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Discipline of Geriatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Renata Elaine Paraizo
authors.initials: RE
authors.lastname: Leite
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Discipline of Geriatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Renata Eloah
authors.initials: RE
authors.lastname: de Lucena Ferreti-Rebustini
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Instituto do Cérebro, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Alexandre Valotta
authors.initials: AV
authors.lastname: da Silva
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Department of Neurology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nitrini
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil.
authors.forename: Carlos Augusto
authors.initials: CA
authors.lastname: Pasqualucci
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil.|Discipline of Geriatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Jacob-Filho
authors.affiliation: Labor für Morphologische Hirnforschung der Klinik und Poliklinik für Psychiatrie und Psychotherapie, Institut Rechtsmedizin, Universitätsklinikum Würzburg, Würzburg, Germany.|Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil.
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
authors.affiliation: Grupo de Estudos em Envelhecimento Cerebral e LIM 22, Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, Av. Dr. Arnaldo, 455 sala 1353, São Paulo, CEP 01246-903, Brazil. lea.grinberg@ucsf.edu.|Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA. lea.grinberg@ucsf.edu.|Department of Pathology, Faculdade de Medicina da Universidade de Sao Paulo, São Paulo, Brazil. lea.grinberg@ucsf.edu.
authors.forename: Lea Tenenholz
authors.initials: LT
authors.lastname: Grinberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002452:Cell Count; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D013378:Substantia Nigra / Q000033:anatomy & histology* / Q000166:cytology / Q000502:physiology*
keywords: 3D reconstruction; Aging brain; Celloidin mounting; Stereology; Substantia nigra