Correction to: A microfluidic platform for continuous monitoring of dopamine homeostasis in dopaminergic cells.

[This corrects the article DOI: 10.1038/s41378-019-0049-2.].

A microfluidic platform for continuous monitoring of dopamine homeostasis in dopaminergic cells.

Homeostasis of dopamine, a classical neurotransmitter, is a key indicator of neuronal health. Dysfunction in the regulation of dopamine is implicated in a long list of neurological disorders, including addiction, depression, and neurodegeneration. The existing methods used to evaluate dopamine homeostasis in vitro are inconvenient and do not allow for continuous non-destructive measurement. In response to this challenge, we introduce an integrated microfluidic system that combines dopaminergic cell culture and differentiation with electroanalytical measurements of extracellular dopamine in real-time at any point during an assay. We used the system to examine the behavior of differentiated SH-SY5Y cells upon exposure to four dopamine transporter ant/agonists (cocaine, ketamine, epigallocatechin gallate, and amphetamine) and study their pharmacokinetics. The IC50 values of cocaine, ketamine, and epigallocatechin gallate were determined to be (average ± standard deviation) 3.7 ± 1.1 µM, 51.4 ± 17.9 µM, and 2.6 ± 0.8 µM, respectively. Furthermore, we used the new system to study amphetamine-mediated dopamine release to probe the related phenomena of dopamine transporter-mediated reverse-transport and dopamine release from vesicles. We propose that this platform, which is the first platform to simultaneously evaluate uptake and release, could be useful to screen for drugs and other agents that target dopaminergic neurons and the function of the dopamine transporter. More broadly, this platform should be adaptable for any application that could benefit from high-temporal resolution electroanalysis combined with multi-day cell culture using small numbers of cells.

A microfluidic method for dopamine uptake measurements in dopaminergic neurons.

Dopamine (DA) is a classical neurotransmitter and dysfunction in its synaptic handling underlies many neurological disorders, including addiction, depression, and neurodegeneration. A key to understanding DA dysfunction is the accurate measurement of dopamine uptake by dopaminergic neurons. Current methods that allow for the analysis of dopamine uptake rely on standard multiwell-plate based ELISA, or on carbon-fibre microelectrodes used in in vivo recording techniques. The former suffers from challenges associated with automation and analyte degradation, while the latter has low throughput and is not ideal for laboratory screening. In response to these challenges, we introduce a digital microfluidic platform to evaluate dopamine homeostasis in in vitro neuron culture. The method features voltammetric dopamine sensors with limit of detection of 30 nM integrated with cell culture sites for multi-day neuron culture and differentiation. We demonstrate the utility of the new technique for DA uptake assays featuring in-line culture and analysis, with a determination of uptake of approximately ∼32 fmol in 10 min per virtual microwell (each containing ∼200 differentiated SH-SY5Y cells). We propose that future generations of this technique will be useful for drug discovery for neurodegenerative disease as well as for a wide range of applications that would benefit from integrated cell culture and electroanalysis.

Investigating degeneration of the retina in young and aged tau P301L mice.

AIMS: Tau is a microtubule-binding protein facilitating the stability of the cytoskeleton. It is important for neurons as several neurodegenerative diseases involve hyperphosphorylation and aggregation of tau. It is known that mutated tau P301L results in aggregation of tau proteins, leading to neuronal loss in the brain. The aim of this study was to investigate the effect of tau mutation on the retina using a transgenic tau P301L mouse model. MAIN METHODS: Morphometric analysis was utilized to quantify the neurodegenerative changes, including the thickness of the inner nuclear layer (INL), and the density and size of retinal ganglion cells (RGCs). Sections of retina tissue stained by hematoxylin and eosin (H&E) and immunohistochemistry were analyzed. Comparisons were made between the tau P301L mice and control mice, as well as between different age groups. KEY FINDINGS: A significant decrease in the thickness of the INL in tau P301L mice was found when compared with that of control mice. The effect was more pronounced in the peripheral area, and the effect increased with age. Regarding density of RGCs, tau P301L mice showed a similar age-related decline as in control mice. Furthermore, the RGCs from tau P301L mice increased in size with age, and the RGCs from control mice decreased in size with age. SIGNIFICANCE: Tau may be an age-independent factor of accelerated neurodegeneration, with effects differing by types of neurons and regions of the retina.

Review: tauopathy in the retina and optic nerve: does it shadow pathological changes in the brain?

Tau protein's versatility lies in its functions within the central nervous system, including protein scaffolding and intracellular signaling. Tauopathy has been one of the most extensively studied neuropathologies among the neurodegenerative diseases. Because the retina and optic nerve are parts of the central nervous system, we hypothesize that tauopathy also plays a role in various eye diseases. However, little is known about tauopathy in the retina and optic nerve. Here, we summarize the findings from histopathological studies on animal models and human specimens with distinct neurodegenerative diseases. Similar pathological changes of tau protein can be found in Alzheimer's disease, frontotemporal lobe dementia, and glaucoma. In view of the important roles of tauopathy in the brain, it is hoped that this review can stimulate research on eye diseases of the retina and optic nerve.

Nutraceuticals and their preventive or potential therapeutic value in Parkinson's disease.

Parkinson's disease (PD) is the second most common aging-related disorder in the world, after Alzheimer's disease. It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and other parts of the brain, leading to motor impairment, cognitive impairment, and dementia. Current treatment methods, such as L-dopa therapy, are focused only on relieving symptoms and delaying progression of the disease. To date, there is no known cure for PD, making prevention of PD as important as ever. More than a decade of research has revealed a number of major risk factors, including oxidative stress and mitochondrial dysfunction. Moreover, numerous nutraceuticals have been found to target and attenuate these risk factors, thereby preventing or delaying the progression of PD. These nutraceuticals include vitamins C, D, E, coenzyme Q10, creatine, unsaturated fatty acids, sulfur-containing compounds, polyphenols, stilbenes, and phytoestrogens. This review examines the role of nutraceuticals in the prevention or delay of PD as well as the mechanisms of action of nutraceuticals and their potential applications as therapeutic agents, either alone or in combination with current treatment methods.