Applications of Unbiased Stereology to Neurodevelopmental Toxicology

Author(s):  
Peter R. Mouton
Keyword(s):  
Author(s):  
Vyvyan Howard ◽  
Matthew Reed
Keyword(s):  

Neurology ◽  
2018 ◽  
Vol 90 (5) ◽  
pp. e396-e403 ◽  
Author(s):  
Garam Kim ◽  
Shahrooz Vahedi ◽  
Tamar Gefen ◽  
Sandra Weintraub ◽  
Eileen H. Bigio ◽  
...  

ObjectiveTo quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA).MethodsPhosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language- and memory-related cortical regions.ResultsClinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere.ConclusionsThe distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.


2005 ◽  
Vol 145 (1-2) ◽  
pp. 37-46 ◽  
Author(s):  
Ivan Lopez ◽  
Gail Ishiyama ◽  
Yong Tang ◽  
Michael Frank ◽  
Robert W Baloh ◽  
...  

2005 ◽  
Vol 289 (2) ◽  
pp. F273-F279 ◽  
Author(s):  
Hayley Dickinson ◽  
David W. Walker ◽  
Luise Cullen-McEwen ◽  
E. Marelyn Wintour ◽  
Karen Moritz

The spiny mouse is relatively mature at birth. We hypothesized that like other organs, the kidney may be more developed in the spiny mouse at birth, than in other rodents. If nephrogenesis is complete before birth, the spiny mouse may provide an excellent model with which to study the effects of an altered intrauterine environment on renal development. Due to its desert adaptation, the spiny mouse may have a reduced cortex-to-medulla ratio but an equivalent total nephron number to the C57/BL mouse. Kidneys were collected from fetal and neonatal spiny mice and sectioned for gross examination of metanephric development. Kidneys were collected from adult spiny mice (10 wk of age), and glomerular number, volume, and cortex-to-medulla ratios were determined using unbiased stereology. Nephrogenesis is complete in spiny mouse kidneys before birth. Metanephrogenesis begins at ∼ day 18, and by day 38 of a 40-day gestation, the nephrogenic zone is no longer present. Spiny mice have a significantly ( P < 0.001) lower total nephron number compared with C57/BL mice, although the total glomerular volume is similar. The cortex-to-medulla ratio of the spiny mouse is significantly ( P < 0.01) smaller. The spiny mouse is the first rodent species shown to complete nephrogenesis before birth. This makes it an attractive candidate for the study of fetal and neonatal kidney development and function. The reduced total nephron number and cortex-to-medulla ratio in the spiny mouse may contribute to its ability to highly concentrate its urine under stressful conditions (i.e., dehydration).


1997 ◽  
Vol 68 (2-3) ◽  
pp. 177-178
Author(s):  
T. Sharma ◽  
S.W.L. Lewis ◽  
T. Sigmundsson ◽  
E. Lancaster ◽  
P. Barta ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Bunmi Ojo ◽  
Heather Davies ◽  
Payam Rezaie ◽  
Paul Gabbott ◽  
Francis Colyer ◽  
...  

Advanced ageing is associated with hippocampal deterioration and mild cognitive decline. The hippocampal subregion CA3 stratum lucidum (CA3-SL) receives neuronal inputs from the giant mossy fibre boutons of the dentate gyrus, but relatively little is known about the integrity of this synaptic connection with ageing. Using serial electron microscopy and unbiased stereology, we examined age-related changes in mossy fibre synapses on CA3 thorny excrescences within the CA3-SL of young adults (4-month-old), middle-aged (12-month-old), and old-aged (28-month-old) Wistar rats. Our data show that while there is an increase in CA3 volume with ageing, there is a significant (40–45%) reduction in synaptic density within the CA3-SL of 12- and 28-month-old animals compared with 4-month-old animals. We also present preliminary data showing that the CA3 neuropil in advanced ageing was conspicuously full of lipofuscin and phagolysosome positive, activated microglial cellular processes, and altered perivascular pathology. These data suggest that synaptic density in the CA3-SL is significantly impaired in ageing, accompanied by underlying prominent ultrastructural glial and microvascular changes.


Author(s):  
Mark Burke ◽  
Shahin Zangenehpour ◽  
Peter R. Mouton ◽  
Maurice Ptito

2002 ◽  
Vol 112 (3) ◽  
pp. 526-533 ◽  
Author(s):  
Yong Tang ◽  
Ivan Lopez ◽  
Akira Ishiyama

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