Threedimensional and stereological characterizati

Authors: 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 FerretiRebustini Alexandre Valotta da Silva Ricardo Nitrini Carlos Augusto Pasqualucci Wilson JacobFilho Helmut Heinsen Lea Tenenholz Grinberg

Publish Date: 2015/09/19

Volume: 221, Issue: 7, Pages: 3393-3403

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Abstract

The human brain undergoes nonuniform 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 agerelated neurodegenerative diseases To establish normative data for highresolution 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 formalinfixed celloidinmounted serially cut and Nisslstained The shapes of all SNs investigated were reconstructed using fast highresolution computerassisted 3D reconstruction software We found a negative correlation between age and SN volume p = 004 rho = −053 with great variability in neuronal numbers and density across participants The 3D reconstructions revealed SN inter and intraindividual 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 SNWe are grateful to the families that donated brains for this research We would also like to thank all the members of the Brain Bank of the Brazilian Aging Brain Study Group We are grateful to Prof Dr Edson Amaro Junior for scientific collaboration and Dr Eduardo Alho for technical support in 3D reconstruction We also thank Dr Janet Johnston http//wwwoutputie for language editing Funding sources Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior CAPES Institute for Education and Research of Albert Einstein Hospital São Paulo Research Foundation FAPESP Brazilian National Council for Scientific and Technological Development CNPq LIM22 HCFMUSP for research financial and technical support in Brazil and the National Institutes of Health USA R01AG040311All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

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