The Use of Recently Developed Histochemical Markers for Localizing Neurotoxicant Induced Regional Brain Pathologies

Sarkar, Sumit; Raymick, James; Schmued, Larry C.

doi:10.3390/toxins6041453

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…Furthermore, we propose to use Fluoro Jade C, a histochemical technique currently used only to detect neurodegeneration in animal models, for human autoptic diagnoses. 24 , 25 …”

Section: Introductionmentioning

confidence: 99%

From fix to fit into the autoptic human brains

et al. 2018

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Formalin-fixed, paraffin embedded (FFPE) human brain tissues are very often stored in formalin for long time. Formalin fixation reduces immunostaining, and the DNA/RNA extraction from FFPE brain tissue becomes suboptimal. At present, there are different protocols of fixation and several procedures and kits to extract DNA/RNA from paraffin embedding tissue, but a gold standard protocol remains distant. In this study, we analysed four types of fixation systems and compared histo- and immunostaining. Based on our results, we propose a modified method of combined fixation in formalin and formic acid for the autoptic adult brain to obtain easy, fast, safe and efficient immunolabelling of long-stored FFPE tissue. In particular, we have achieved an improved preservation of cellular morphology and obtained success in post-mortem immunostaining for NeuN. This nuclear antigen is an important marker for mapping neurons, for example, to evaluate the histopathology of temporal lobe epilepsy or to draw the topography of cardiorespiratory brainstem nuclei in sudden infant death syndrome (SIDS). However, NeuN staining is frequently faint or lost in post-mortem human brain tissues. In addition, we attained Fluoro Jade C staining, a marker of neurodegeneration, and immunofluorescent staining for stem cell antigens in the postnatal human brain, utilizing custom fit fixation procedures.

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“…Furthermore, we propose to use Fluoro Jade C, a histochemical technique currently used only to detect neurodegeneration in animal models, for human autoptic diagnoses. 24 , 25 …”

Section: Introductionmentioning

confidence: 99%

From fix to fit into the autoptic human brains

et al. 2018

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“…We next determined the number of amyloid plaques in the cortex of the treated and untreated APP/PS1 mice using Amylo-glo [ 50 ]. We observed a significant reduction in the number of plaques in the cortex of the treated versus the placebo mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer’s phenotypes without blocking peripheral T cell IL-2 response

Stallings,

O’Neal,

et al. 2023

Alz Res Therapy

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Background Current treatments for Alzheimer’s disease (AD) have largely failed to yield significant therapeutic benefits. Novel approaches are desperately needed to help address this immense public health issue. Data suggests that early intervention at the first stages of mild cognitive impairment may have a greater chance for success. The calcineurin (CN)-Pin1 signaling cascade can be selectively targeted with tacrolimus (FK506), a highly specific, FDA-approved CN inhibitor used safely for > 20 years in solid organ transplant recipients. AD prevalence was significantly reduced in solid organ recipients treated with FK506. Methods Time release pellets were used to deliver constant FK506 dosage to APP/PS1 mice without deleterious manipulation or handling. Immunofluorescence, histology, molecular biology, and behavior were used to evaluate changes in AD pathology. Results FK506 can be safely and consistently delivered into juvenile APP/PS1 mice via time-release pellets to levels roughly seen in transplant patients, leading to the normalization of CN activity and reduction or elimination of AD pathologies including synapse loss, neuroinflammation, and cognitive impairment. Pin1 activity and function were rescued despite the continuing presence of high levels of transgenic Aβ42. Indicators of neuroinflammation including Iba1 positivity and IL-6 production were also reduced to normal levels. Peripheral blood mononuclear cells (PBMC) obtained during treatment or splenocytes isolated at euthanasia activated normally after mitogens. Conclusions Low-dose, constant FK506 can normalize CNS CN and Pin1 activity, suppress neuroinflammation, and attenuate AD-associated pathology without blocking peripheral IL-2 responses making repurposed FK506 a viable option for early, therapeutic intervention in AD.

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“…A typical commercial reagent for amyloid staining is "Amylo-Glo" [58][59][60][61]: Compound [53]: "Amylo-glo"; specification: Styrylbenzene derivative; Appearance: Yellow solution; Molecular Weight: 392; Filter system for visualizing: UV Ethibium Bromide: EtBr, 2,7-Diamino-10-ethyl-6-phenylphenanthridinium bromide; Appearance: light red-orange solution; Molecular Weight: 394.32. 392; Filter system for visualizing: UV Purity: Thin layer chromatography using alumina plates and a solvent system of ethanol and water (3:1) revealed the presence of two fluorescent isomers.…”

Section: Staining Amyloid-betamentioning

confidence: 99%

Glutathione As Biomarker for Neurodegenerative Diseases

2020

J B & Bio Engine;

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Brain imaging is one of the main obstacles of modern disease diagnostics since it must allow accurate and quantitative measurements on a living organ that is placed in adults (in neonatal humans’ skull penetration is somewhat easier) inside a bone cage. Inside is the brain, the main function controller of our body that must be done in a non- invasive way on the living operation brain. Many spectroscopic methods are trying to overcome the difficult access to the brain: Photoacoustic microscopy, Confocal microscopy, Two-photon microscopy, Optical coherence tomography, Scanning Laser Acoustic Microscopy, Acoustic microscopy, Ultrasonography, positron tomography, fluorescence methods, photo caustic microscopy and multi (two) photon imaging spectroscopy. The situation is complex since the brain is wrapped in the blood brain barrier allowing only selected molecules to pass from the blood stream to and out of the brain. In this chapter, we will survey the current situation of brain diagnostics with the aid of the spectroscopic methods. Brain research is integrated in aging research as a major area of interest. Aging is in most cased coupled with the loss of brain function and dementia. The neurodegenerative diseases, although identified by Dr. Alzheimer and his collaborators more than a century ago, continue as the leading causes of mortality among the elderly. Brain research in trying to give hope to those people but unfortunately our understanding in this area is limited. Oxidative stress contributes to neurodegenerative diseases pathophysiology and progression. The target was to describe central and peripheral metabolites of redox metabolism and to describe correlations between glutathione status, age, and disease severity.

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The Use of Recently Developed Histochemical Markers for Localizing Neurotoxicant Induced Regional Brain Pathologies

Cited by 5 publications

References 52 publications

From fix to fit into the autoptic human brains

From fix to fit into the autoptic human brains

Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer’s phenotypes without blocking peripheral T cell IL-2 response

Glutathione As Biomarker for Neurodegenerative Diseases

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