Stereological length estimation using spherical probes

Mouton, Peter R.; Gokhale, A.M.; Ward, Nicole L.; West, Mark J.

doi:10.1046/j.1365-2818.2002.01006.x

Cited by 179 publications

(166 citation statements)

References 20 publications

(30 reference statements)

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…The density of the TH-positive innervation was assessed using a modified "sphere counting" technique of Mouton et al (17,18). Using a 100× oilimmersion objective, in a bright-field microscope (Olympus AX70), a z-stack was captured throughout the entire thickness of the section at 1-μm intervals, using Velocity v5.4.2 image analysis software (PerkinElmer).…”

Section: Methodsmentioning

confidence: 99%

Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain

Englund

Widner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

246

233

View full text Add to dashboard Cite

Clinical trials using cells derived from embryonic ventral mesencephalon have shown that transplanted dopaminergic neurons can survive and function in the long term, as demonstrated by in vivo brain imaging using 18F-fluorodopa and 11C-raclopride positron emission tomography. Here we report the postmortem analysis of a patient with Parkinson’s disease who 24 y earlier underwent unilateral transplantation of embryonic dopaminergic neurons in the putamen and subsequently exhibited major motor improvement and recovery of striatal dopaminergic function. Histopathological analysis showed that a dense, near-normal graft-derived dopaminergic reinnervation of the putamen can be maintained for a quarter of a century despite severe host brain pathology and with no evidence of immune response. In addition, ubiquitin- and α-synuclein–positive inclusions were seen, some with the appearance of typical Lewy bodies, in 11–12% of the grafted dopaminergic neurons, reflecting the spread of pathology from the host brain to the transplants. Because the clinical benefits induced by transplantation in this patient were gradually lost after 14 y posttransplantation, our findings provide the first reported evidence, to our knowledge, that even a viable dopaminergic graft giving rise to extensive striatal reinnervation may lose its efficacy if widespread degenerative changes develop in the host brain.

show abstract

Section: Methodsmentioning

confidence: 99%

Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain

Englund

Widner

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

246

233

View full text Add to dashboard Cite

show abstract

“…5 reactive NT length in the sections described above. 74 The surface area of the spaceball was kept constant at 402.124 m. The total area counted was dependent on the amount of pS422ϩ NTs and ranged from 0.42% to 0.04% of the area outlined, optimized to count of 200 to 400 pS422ϩ NTs per case. CE values were calculated to determine the accuracy of the counts (Table 2).…”

Section: Stereological Quantification Of Neurons and Nt Lengthmentioning

confidence: 99%

Progression of Tau Pathology in Cholinergic Basal Forebrain Neurons in Mild Cognitive Impairment and Alzheimer's Disease

Vana

Kanaan

Ugwu

et al. 2011

The American Journal of Pathology

105

109

View full text Add to dashboard Cite

Tau is a microtubule-associated protein that forms neurofibrillary tangles (NFTs) in the selective vulnerable long projection neurons of the cholinergic basal forebrain (CBF) in Alzheimer's disease (AD). Although CBF neurodegeneration correlates with cognitive decline during AD progression, little is known about the temporal changes of tau accumulation in this region. We investigated tau posttranslational modifications during NFT evolution within the CBF neurons of the nucleus basalis (NB) using tissue from subjects with no cognitive impairment, mild cognitive impairment, and AD. The pS422 antibody was used as an early tau pathology marker that labels tau phosphorylated at Ser422; the TauC3 antibody was used to detect later stage tau pathology. Stereologic evaluation of NB tissue immunostained for pS422 and TauC3 revealed an increase in neurons expressing these tau epitopes during disease progression. We also investigated the occurrence of pretangle tau events within cholinergic NB neurons by dual staining for the cholinergic cell marker, p75 NTR , which displays a phenotypic down-regulation within CBF perikarya in AD. As pS422؉ neurons increased in number, p75 NTR ؉ neurons decreased, and these changes correlated with both AD neuropathology and cognitive decline. Also, NFTs developed slower in the CBF compared with previously examined cortical regions. Taken together, these results suggest that changes in cognition are associated with pretangle events within NB cholinergic neurons before frank Degeneration of the cholinergic basal forebrain (CBF) neurons, which provide the major cholinergic innervation to the entire cortical mantle, hippocampus, and amygdala 1,2 correlates with dementia severity, disease duration, and cognitive impairment 3,4 in Alzheimer's disease (AD). 3,5-9 The viability of CBF neurons is dependent on the prototypic neurotrophic substance, nerve growth factor (NGF), 10 which is retrogradely transported to CBF neurons through a complex interaction of its two receptors, the high-affinity NGF-specific cell survival tyrosine kinase (trkA) and the putative cell death associated lowaffinity pan neurotrophin (p75 NTR ) receptor. 11,12 Previous studies have identified critical changes within the basocortical cholinergic system during the progression of AD, indicating a shift in the balance from pro-survival to apoptotic mechanisms, before frank cellular alteration, 13,14 which likely over time plays a mechanistic role in the CBF degeneration seen in AD. 5 In addition to altered neurotrophic factor dysfunction coincident with disease progression, CBF neurons also develop intracellular inclusions that appear as globose neurofibrillary tangles (NFTs) and neuropil threads (NTs), hallmark tau pathologies found in AD. [15][16][17] Tau is a microtubule-associated protein involved in normal cytoskeleton function, 18,19 but in AD tau transitions from its relatively soluble state into filamentous aggregates. 20 Braak and colleagues delineated six stages (I to VI) related to the spatial temporal distribution a...

show abstract

“…Axon length was assessed using the SpaceBalls probe under Koehler illumination at 63x (Zeiss PlanAchromat, N.A. 1.4) (Calhoun and Mouton, 2000;Mouton et al, 2002;Calhoun et al, 2004;Kreczmanski et al, 2005). SpaceBalls is a stereological tool that places sampling hemispheres for lineal features in the context of a fractionator sampling scheme (Mouton, 2002).…”

Section: Axon Length Densitymentioning

confidence: 99%

Cortical dopaminergic innervation among humans, chimpanzees, and macaque monkeys: A comparative study

et al. 2008

View full text Add to dashboard Cite

In this study, we assessed the possibility that humans differ from other primate species in the supply of dopamine to the frontal cortex. To this end, quantitative comparative analyses were performed among humans, chimpanzees, and macaques using immunohistochemical methods to visualize tyrosine hydroxylase-immunoreactive axons within the cerebral cortex. Axon densities and neuron densities were quantified using computer-assisted stereology. Areas 9 and 32 were chosen for evaluation due to their roles in higher-order executive functions and theory of mind, respectively. Primary motor cortex (area 4) was also evaluated because it is not directly associated with cognition. We did not find an overt quantitative increase in cortical dopaminergic innervation in humans relative to the other primates examined. However, several differences in cortical dopaminergic innervation were observed among species which may have functional implications. Specifically, humans exhibited a sublaminar pattern of innervation in layer I of areas 9 and 32 that differed from that of macaques and chimpanzees. Analysis of axon length density to neuron density among species revealed that humans and chimpanzees together deviated from macaques in having increased dopaminergic afferents in layers III and V/VI of areas 9 and 32, but there were no phylogenetic differences in area 4. Finally, morphological specializations of axon coils that may be indicative of cortical plasticity events were observed in humans and chimpanzees, but not macaques. Our findings suggest significant modifications of dopamine's role in cortical organization occurred in the evolution of the apes, with further changes in the descent of humans.

show abstract

Stereological length estimation using spherical probes

Cited by 179 publications

References 20 publications

Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain

Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain

Progression of Tau Pathology in Cholinergic Basal Forebrain Neurons in Mild Cognitive Impairment and Alzheimer's Disease

Cortical dopaminergic innervation among humans, chimpanzees, and macaque monkeys: A comparative study

Contact Info

Product

Resources

About