In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining

Tatton, Nadine; Kish, Stephen J.

doi:10.1016/s0306-4522(96)00545-3

Cited by 434 publications

(306 citation statements)

References 45 publications

Supporting

Mentioning

276

Contrasting

Unclassified

Order By: Relevance

“…Its metabolite, MPP ϩ , is a potent inhibitor of mitochondrial NADHlinked electron transport at Complex I resulting in the loss of ATP production and subsequent cell death. A recent study demonstrates that MPTP can elicit apoptotic nuclei in the substantia nigra compacta (39). However, the type of cell death and its associated mechanisms induced by this neurotoxin are still controversial.…”

Section: Introductionmentioning

confidence: 99%

Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

Choi

Canzoniero

Sensi

et al. 1999

Experimental Neurology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

Choi

Canzoniero

Sensi

et al. 1999

Experimental Neurology

View full text Add to dashboard Cite

“…2A) and is compatible with confocal microscopy. 158,160 Quantitative analysis of double-labeled sections demonstrates approximately 55% of TSstained SPs also contain AO labeling, 31,158 indicating the presence of RNA species in a significant population of SPs. The observed sequestration of RNA SPs in AD and related disorders prompted single cell analysis of SPs in sections of AD hippocampus.…”

Section: Expression Profile Analysis Of Senile Plaques In the Ad Hippmentioning

confidence: 99%

Single cell gene expression profiling in Alzheimer’s disease

et al. 2006

View full text Add to dashboard Cite

Summary: Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

show abstract

“…MPTP, as well as its active metabolite MPP + (1-methyl-4-phenylpyridinium), can induce an inflammatory response [16,17] and the death of DN by apoptotic pathway in the substantia nigra pars compacta (SNc) in mouse [18] . MPTP will preferentially produce an inflammatory process after an acute treatment (4 × 20 mg/kg i.p.…”

Section: Introductionmentioning

confidence: 99%

“…MPTP will preferentially produce an inflammatory process after an acute treatment (4 × 20 mg/kg i.p. every 2 h on one day) [19] and neuronal cell death after a chronic treatment (30 mg/kg/day during 5 consecutive days) [18,20] . The MPTP mouse model of PD and MPP + cell exposure both lead to apoptosis and TNF-α release and offer a good model for in vivo and in vitro Parkinson's studies.…”

Section: Introductionmentioning

confidence: 99%

Targeting of cell death and neuroinflammation with peptide-linked iron oxide nanoparticles and Gd-DTPA in a mouse model of Parkinson's disease

Sclavons

Boutry²,

Laurent

et al. 2015

JBEI

View full text Add to dashboard Cite

Parkinson's disease (PD) is one of the most common neurodegenerative disease and remains difficult to diagnose by conventional methods of early detection. It is characterized by the apoptotic loss of dopaminergic neurons (DN) and a neuroinflammation mainly located in the ventral midbrain (VM).The aim of this work is to study new vectorized contrast agents for magnetic resonance imaging (MRI) detection of PD injured areas by targeting apoptosis and inflammation. Two peptides selected by phage display were used for the experiments: R826 peptide, selected for its affinity for the phosphatidylserine (PS) exposed at the external surface of apoptotic cells, and 2C peptide, selected for its affinity for TNF-α (tumor necrosis factor alpha), one of the most abundant cytokines secreted during inflammation. These peptides were grafted to pegylated iron oxide nanoparticles (PEG-USPIO) and gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) for in vitro and in vivo studies, respectively. PD was simulated on mice with the MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) neurotoxin and its active metabolite MPP + (1-methyl-4-phenylpyridinium) for in vitro studies.The results showed that PEG-USPIO-R826 and PEG-USPIO-2C enabled the detection of apoptosis and inflammation, respectively, on MPP + -treated culture cells. PEG-USPIO-2C also allowed detection of inflammation on histological brain sections of MPTP-treated mice. The 2C peptide grafted to Gd-DTPA showed encouraging results in MRI detection of injured brain areas in MPTP-treated mice. These observations suggest that a targeting of damaged cells and injured areas by these new specific contrast agents occurs, offering a new tool for early diagnosis of neurodegenerative disorders like PD by MRI.

show abstract

In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining

Cited by 434 publications

References 45 publications

Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

Single cell gene expression profiling in Alzheimer’s disease

Targeting of cell death and neuroinflammation with peptide-linked iron oxide nanoparticles and Gd-DTPA in a mouse model of Parkinson's disease

Contact Info

Product

Resources

About