Estimates of Intracellular Dopamine in Parkinson's Disease: A Systematic Review and Meta-Analysis.

J Parkinsons Dis

Principal, ExVivos, LLC, Hastings-on-Hudson, NY, USA.

Published: January 2022

Background: The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease progression. However, intraneuronal levels of dopamine have not been reported.

Objective: Meta-analytic methods were utilized to determine intracellular dopamine levels in Parkinson's disease.

Methods: A systematic review of the literature and frequentist meta-analyses were performed. Dopamine levels were scaled for cell and axon numbers as well as VMAT2 protein levels.

Results: Reduced tissue dopamine, dopaminergic cell bodies and VMAT2 protein were confirmed. The ratio of Parkinson's to normal brain intracellular dopamine scaled for either cell or axon number, each with VMAT2 level in the caudate ranged from 1.49 to 1.87 (p = 0.51 and p = 0.12, respectively) and in the putamen from 0.75 to 4.61 (p = 0.40 and 0.001, respectively).

Conclusion: Free, intracellular dopamine levels are not reduced in Parkinson's disease compared to normals to a similar degree as are total tissue concentrations, supporting the relevance of modulating VMAT2, neuromelanin and/or dopamine synthesis as rational neuroprotective strategies.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461729PMC
http://dx.doi.org/10.3233/JPD-212715DOI Listing

Publication Analysis

Top Keywords

intracellular dopamine
16
parkinson's disease
16
dopamine levels
12
dopamine
10
systematic review
8
scaled cell
8
cell axon
8
vmat2 protein
8
parkinson's
6
disease
5

Similar Publications

The concentrations of extracellular and intracellular signaling molecules, such as dopamine and cAMP, change over both fast and slow timescales and impact downstream pathways in a cell-type specific manner. Fluorescence sensors currently used to monitor such signals are typically optimized to detect fast, relative changes in concentration of the target molecule. They are less well suited to detect slowly-changing signals and rarely provide absolute measurements of either fast and slow signaling components.

View Article and Find Full Text PDF

Habitual consumption of low-calorie sweeteners (LCS) during juvenile-adolescence can lead to greater sugar intake later in life. Here, we investigated if exposure to the LCS Acesulfame Potassium (Ace-K) during this critical period of development reprograms the taste system in a way that would alter hedonic responding for common dietary compounds. Results revealed that early-life LCS intake not only enhanced the avidity for a caloric sugar (fructose) when rats were in a state of caloric need, it increased acceptance of a bitterant (quinine) in Ace-K-exposed rats tested when middle-aged.

View Article and Find Full Text PDF

Localization of Melanocortin 1 Receptor in the Substantia Nigra.

Int J Mol Sci

December 2024

Department of Anatomy, Dokkyo Medical University School of Medicine, 880 Kita-Kobayashi, Mibu-machi, Shimotsuga-gun 321-0293, Tochigi, Japan.

Article Synopsis
  • Recent research indicates that a deficiency in the melanocortin 1 receptor (MC1R) is linked to neurodegeneration similar to Parkinson's disease in a specific brain region called the substantia nigra (SN).
  • The study used techniques like in situ hybridization and immunohistochemistry to identify the location and characteristics of MC1R, finding it mostly in susceptible dopaminergic neurons and in a type of inhibitory neuron known as parvalbumin (PV)-positive neurons.
  • The results show that MC1R is involved not only in the cell membrane but also in organelles like mitochondria, suggesting that it, along with a modulator called attractin (Atrn), plays an important role in
View Article and Find Full Text PDF

Detection of Human GPCR Activity in Drosophila S2 Cells Using the Tango System.

Int J Mol Sci

December 2024

Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Osaka 920-1192, Japan.

G protein-coupled receptors (GPCRs) are essential cell surface proteins involved in transducing extracellular signals into intracellular responses, regulating various physiological processes. This study validated the use of the Tango assay, a sensitive method for detecting GPCR activation, in Schneider 2 (S2) cells, focusing on the human Dopamine Receptor D4 (DRD4). Plasmids encoding the LexA-tagged human DRD4 receptor and a luciferase reporter were co-transfected into S2 cells and stimulated with dopamine.

View Article and Find Full Text PDF

In silico drug repurposing at the cytoplasmic surface of human aquaporin 1.

PLoS One

January 2025

Genome and Structural Bioinformatics Group, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, Wales, United Kingdom.

Aquaporin 1 (AQP1) is a key channel for water transport in peritoneal dialysis. Inhibition of AQP1 could therefore impair water transport during peritoneal dialysis. It is not known whether inhibition of AQP1 occurs unintentionally due to off-target interactions of administered medications.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!