Age‐related and regional differences in dopamine transporter mRNA expression in human midbrain

Bannon, Michael J.; Whitty, Christopher J. M.

doi:10.1212/wnl.48.4.969

Cited by 120 publications

(89 citation statements)

References 4 publications

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“…It is unclear whether increasing passage number of a cultured cell line can be correlated to cell aging. Moreover, the number of available DAT sites in the brain decreases with aging (Bannon and Whitty, 1997;Salvatore et al, 2003), in contrast with the present CHO cell findings. For each of the classical DAT blockers cocaine, mazindol, methylphenidate and benztropine, DUIP IC 50 values differed significantly between "low passage" and "high passage" WT DAT CHO cells.…”

Section: Discussioncontrasting

confidence: 99%

Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

Ukairo¹,

Ramanujapuram²,

Surratt³

2007

Brain Research

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Cocaine, amphetamines and other psychostimulants inhibit synaptic dopamine uptake by interfering with dopamine transporter (DAT) function. The resultant potentiation of dopaminergic neurotransmission is associated with psychostimulant addiction. Fluctuations in dopamine uptake inhibition potency (DUIP) were observed for classical DAT blockers including cocaine, mazindol, methylphenidate (Ritalin™) and benztropine in CHO cells expressing wildtype DAT; cocaine potency also decreased in DAT-expressing non-neuronal COS-7 cells and neuronal N2A neuroblastoma cells. In contrast, the DAT substrate (+)-amphetamine did not display this DUIP fluctuation. In parallel experiments, no fluctuation was observed for the apparent binding affinities of these 5 drugs. The DUIP decrease appeared to correlate with an increase in cell surface DAT expression level, as measured by B max values and confocal microscopy. The fact that the DUIP profile of amphetamine diverged from that of the classical DAT blockers is consistent with the idea of fundamental differences between the mechanisms of abused psychostimulant DAT substrates and inhibitors. Identification of the cellular factors that underlie the DAT inhibitor DUIP fluctuation phenomenon may be relevant to anti-psychostimulant drug discovery efforts.

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Section: Discussioncontrasting

confidence: 99%

Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

Ukairo¹,

Ramanujapuram²,

Surratt³

2007

Brain Research

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“…Postmortem brain specimens were obtained from Miami, Florida (study 1) and Wayne County, Michigan (study 2) during routine autopsy and analyzed as described (10,11). Medicolegal investigations were conducted by forensic pathologists.…”

Section: Methodsmentioning

confidence: 99%

“…In situ hybridization was carried out as described (11,13). Midbrain sections (Ϸ12 m thick) from different subjects were matched with regard to rostrocaudal plane and processed in parallel by using 35 S-labeled antisense riboprobes for hNURR1 (nucleotides 7,822-8,199 from GenBank accession no.…”

Section: Methodsmentioning

confidence: 99%

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Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Bannon

Pruetz

Manning-Bog

et al. 2002

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

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Chronic exposure to cocaine induces long-term adaptations that are likely to involve changes in transcription factor expression. This possibility has not been examined in the cocaine-exposed human brain. The transcription factor nurr1 is highly expressed in rodent midbrain dopamine neurons and is essential for their proper phenotypic development. Here we show that human NURR1 gene expression is robust within control subjects and reduced markedly within the dopamine neurons of human cocaine abusers. NURR1 is known to regulate transcription of the gene encoding the cocainesensitive dopamine transporter (DAT). We show here that DAT gene expression also is reduced markedly in the dopamine neurons of NURR1-deficient cocaine abusers, suggesting that NURR1 plays a critical role in vivo in controlling human DAT gene expression and adaptation to repeated exposure to cocaine.

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“…A paradigm that is quite intriguing is aging, particularly within cell types that are vulnerable to neurodegeneration in late-onset progressive neurodegenerative disorders as well as those implicated in neuropsychiatric disorders (91,92). For example, age-related decline in dopamine (DA) receptor levels is observed in regional brain studies of animal models and human postmortem tissues (93)(94)(95)(96). To evaluate potential age-related alterations in DA receptor subtypes in specific cell populations of the hippocampus and entorhinal cortex, single-cell RNA amplification is combined with custom-designed cDNA array analysis to evaluate effects of aging on D1-D5 dopamine receptor mRNA expression levels in hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells from normal control postmortem human brains aged 19-95 years old (6).…”

Section: Single-cell Analysis and Aging: Dopamine Receptor Expressionmentioning

confidence: 99%

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

et al. 2004

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Technical and experimental advances in microaspiration techniques, RNA amplification, quantitative real-time polymerase chain reaction (qPCR), and cDNA microarray analysis have led to an increase in the number of studies of single-cell gene expression. In particular, the central nervous system (CNS) is an ideal structure to apply single-cell gene expression paradigms. Unlike an organ that is composed of one principal cell type, the brain contains a constellation of neuronal and noneuronal populations of cells. A goal is to sample gene expression from similar cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and noneuronal cells. The unprecedented resolution afforded by singlecell RNA analysis in combination with cDNA microarrays and qPCR-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease states. 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 as well as postmortem human brain tissues. This focused review illustrates the potential power of single-cell gene expression studies within the CNS in relation to neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia, respectively. KEY WORDS:Alzheimer's disease; cDNA microarray; cholinergic basal forebrain; dopamine receptors; expression profiling; protein phosphatases; RNA amplification; schizophrenia; single-cell microaspiration. Abbreviations (note the use of the NCBI-Unigene annotation): 3Rtau, three-repeat tau; 4Rtau, four-repeat tau; ACT, alpha-1-antichymotrypsin; ACTB, beta-actin; AGER, advanced glycosylation end product-specific receptor; APOE, apolipoprotein E; APP, amyloid-beta precursor protein; arc, activity regulated cytoskeletal-associated protein; BAX,

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Age‐related and regional differences in dopamine transporter mRNA expression in human midbrain

Cited by 120 publications

References 4 publications

Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

Decreased expression of the transcription factor NURR1 in dopamine neurons of cocaine abusers

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

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