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 fifteen 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.

Quantifying the accretion of hyperphosphorylated tau in the locus coeruleus and dorsal raphe nucleus: the pathological building blocks of early Alzheimer's disease

“…LC and DRN are parts of the isodendritic core and exhibit extremely early susceptibility to develop ADrelated tau cytoskeleton pathology [8,11,12,21]. As the major site of noradrenalin synthesis in the brain, the LC plays a major role in circadian rhythms, depression and stress [13,27,[44][45][46][47][48][49][50]. The DRN produces the majority of the serotonin in the brain and has been associated with psychiatric disorders such as depression [11].…”

The missing, the short, and the long: Levodopa responses and dopamine actions

“…Substantia nigra (SN) dopaminergic neurons constitute a tiny fraction of human brain neurons, with an estimated total of 1.2 million (600,000 per side) neurons. 29 Each neuron of this small population gives rise to large axonal arborizations with particularly dense innervation of dorsal striatal projection neurons. Projections from the most medial portion of the SN complex, the ventral tegmental area, target other forebrain targets such as ventral striatum, frontal cortex, and amygdala.…”

Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation

“…Recorded images were stacked, aligned, and used for 3D reconstruction of the histological volume with the use of specialized software (Amira 5.3®, Mercury Systems). This software generated a surface based on individual outlines, which were manually traced on digital images (Heinsen et al 2004; Di Lorenzo Alho et al 2015). …”