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Biosensors Aug 2023Neurotransmitters are an important category of substances used inside the nervous system, whose detection with biosensors has been seriously addressed in the last... (Review)
Review
Neurotransmitters are an important category of substances used inside the nervous system, whose detection with biosensors has been seriously addressed in the last decades. Dopamine, a neurotransmitter from the catecholamine family, was recently discovered to have implications for cardiac arrest or muscle contractions. In addition to having many other neuro-psychiatric implications, dopamine can be detected in blood, urine, and sweat. This review highlights the importance of biosensors as influential tools for dopamine recognition. The first part of this article is related to an introduction to biosensors for neurotransmitters, with a focus on dopamine. The regular methods in their detection are expensive and require high expertise personnel. A major direction of evolution of these biosensors has expanded with the integration of active biological materials suitable for molecular recognition near electronic devices. Secondly, for dopamine in particular, the miniaturized biosensors offer excellent sensitivity and specificity and offer cheaper detection than conventional spectrometry, while their linear detection ranges from the last years fall exactly on the clinical intervals. Thirdly, the applications of novel nanomaterials and biomaterials to these biosensors are discussed. Older generations, metabolism-based or enzymatic biosensors, could not detect concentrations below the micro-molar range. But new generations of biosensors combine aptamer receptors and organic electrochemical transistors, OECTs, as transducers. They have pushed the detection limit to the pico-molar and even femto-molar ranges, which fully correspond to the usual ranges of clinical detection of human dopamine in body humors that cover 0.1 ÷ 10 nM. In addition, if ten years ago the use of natural dopamine receptors on cell membranes seemed impossible for biosensors, the actual technology allows co-integrate transistors and vesicles with natural receptors of dopamine, like G protein-coupled receptors. The technology is still complicated, but the uni-molecular detection selectivity is promising.
Topics: Humans; Dopamine; Catecholamines; Body Fluids; Biocompatible Materials; Cell Membrane
PubMed: 37622892
DOI: 10.3390/bios13080806 -
Movement Disorders : Official Journal... Feb 2024Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if... (Review)
Review
BACKGROUND
Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if undiagnosed and untreated. While ICBD pathophysiology and risk factors are well-studied, a standardized severity definition and treatment evidence remain elusive.
OBJECTIVE
This work aimed to establish international expert consensus on ICBD treatment strategies. To comprehensively address diverse treatment availabilities, experts from various continents were included.
METHODS
From 2021 to 2023, global movement disorders specialists engaged in a Delphi process. A core expert group initiated surveys, involving a larger panel in three iterations, leading to refined severity definitions and treatment pathways.
RESULTS
Experts achieved consensus on defining ICBD severity, emphasizing regular PD patient screenings for early detection. General treatment recommendations focused on continuous monitoring, collaboration with significant others, and seeking specialist advice for legal or financial challenges. For mild to severe ICBDs, gradual reduction in dopamine agonists was endorsed, followed by reductions in other PD medications. Second-line treatment strategies included diverse approaches like reversing the last medication change, cognitive behavior therapy, subthalamic nucleus deep brain stimulation, and specific medications like quetiapine, clozapine, and antidepressants. The panel reached consensus on distinct treatment pathways for punding and dopamine dysregulation syndrome, formulating therapy recommendations. Comprehensive discussions addressed management strategies for the exacerbation of either motor or non-motor symptoms following the proposed treatments.
CONCLUSION
The consensus offers in-depth insights into ICBD management, presenting clear severity criteria and expert consensus treatment recommendations. The study highlights the critical need for further research to enhance ICBD management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Humans; Parkinson Disease; Consensus; Mental Disorders; Dopamine; Dopamine Agonists; Deep Brain Stimulation; Disruptive, Impulse Control, and Conduct Disorders
PubMed: 38234035
DOI: 10.1002/mds.29700 -
Neuroscience Aug 2023Dopamine (DA) is a critical neuromodulator involved in various brain functions. To understand how DA regulates neural circuits and behaviors in the physiological and... (Review)
Review
Dopamine (DA) is a critical neuromodulator involved in various brain functions. To understand how DA regulates neural circuits and behaviors in the physiological and pathological conditions, it is essential to have tools that enable the direct detection of DA dynamics in vivo. Recently, genetically encoded DA sensors based on G protein-coupled receptors revolutionized this field, as it allows us to track in vivo DA dynamic with unprecedented spatial-temporal resolution, high molecular specificity, and sub-second kinetics. In this review, we first summarize traditional DA detection methods. Then we focus on the development of genetically encoded DA sensors and feature its significance to understanding dopaminergic neuromodulation across diverse behaviors and species. Finally, we present our perspectives about the future direction of the next-generation DA sensors and extend their potential applications. Overall, this review offers a comprehensive perspective on the past, present, and future of DA detection tools, with important implications for the study of DA functions in health and disease.
Topics: Dopamine; Receptors, G-Protein-Coupled
PubMed: 37419404
DOI: 10.1016/j.neuroscience.2023.06.025 -
The Journal of Physiology Aug 2023The experimental study of learning and plasticity has always been driven by an implicit question: how can physiological changes be adaptive and improve performance? For... (Review)
Review
The experimental study of learning and plasticity has always been driven by an implicit question: how can physiological changes be adaptive and improve performance? For example, in Hebbian plasticity only synapses from presynaptic neurons that were active are changed, avoiding useless changes. Similarly, in dopamine-gated learning synapse changes depend on reward or lack thereof and do not change when everything is predictable. Within machine learning we can make the question of which changes are adaptive concrete: performance improves when changes correlate with the gradient of an objective function quantifying performance. This result is general for any system that improves through small changes. As such, physiology has always implicitly been seeking mechanisms that allow the brain to approximate gradients. Coming from this perspective we review the existing literature on plasticity-related mechanisms, and we show how these mechanisms relate to gradient estimation. We argue that gradients are a unifying idea to explain the many facets of neuronal plasticity.
Topics: Neuronal Plasticity; Neurons; Dopamine; Synapses; Brain
PubMed: 37078235
DOI: 10.1113/JP282747 -
The Australian and New Zealand Journal... Sep 2023
Topics: Humans; Dopamine; Schizophrenia
PubMed: 37264935
DOI: 10.1177/00048674231177958 -
Experimental Eye Research Sep 2023The purpose was to quantify ocular dopamine in rabbits after stimulation of the optic nerve head with short-wavelength (blue) light to activate melanopsin expressed in...
The purpose was to quantify ocular dopamine in rabbits after stimulation of the optic nerve head with short-wavelength (blue) light to activate melanopsin expressed in the axons of intrinsically photosensitive retinal ganglion cells (ipRGCs). Dopamine levels in tears, aqueous humor, vitreous body, and retina (including choroid) were quantified after blue light stimulation of the optic nerve head of 15 rabbits with an optical fiber for 1 min, 10 min, or no stimulation (n = 5, each group). The left eye of all rabbits was operated on to introduce the optical fiber and stimulate the optic nerve, while the contralateral eye served as internal control. One minute of blue light stimulation significantly increased dopamine concentration in the vitreous body of the treated eyes compared to the contralateral ones (P = 0.015). Stimulation for 10 min significantly increased dopamine concentration in the vitreous body, as well as the aqueous humor (P < 0.05). Therefore, using an optical fiber approach to stimulate the optic nerve head with blue light significantly increased dopamine concentration in the aqueous humor and the vitreous body. This likely reflects an upregulation of retinal dopamine synthesis that could be attributed to ipRGC activation. However, the data provided in this study fell short of establishing a definitive link between dopamine release and ipRGC activation, mainly due to the lack of evidence supporting the expression of the melanopsin photopigment in the optic nerve.
Topics: Animals; Rabbits; Optic Disk; Dopamine; Retina; Retinal Ganglion Cells; Light; Rod Opsins; Photic Stimulation
PubMed: 37499737
DOI: 10.1016/j.exer.2023.109604 -
Nature Communications Nov 2023The auditory striatum, a sensory portion of the dorsal striatum, plays an essential role in learning and memory. In contrast to its roles and underlying mechanisms in...
The auditory striatum, a sensory portion of the dorsal striatum, plays an essential role in learning and memory. In contrast to its roles and underlying mechanisms in operant conditioning, however, little is known about its contribution to classical auditory fear conditioning. Here, we reveal the function of the auditory striatum in auditory-conditioned fear memory. We find that optogenetically inhibiting auditory striatal neurons impairs fear memory formation, which is mediated through the striatal-amygdala pathway. Using calcium imaging in behaving mice, we find that auditory striatal neuronal responses to conditioned tones potentiate across memory acquisition and expression. Furthermore, nigrostriatal dopaminergic projections plays an important role in modulating conditioning-induced striatal potentiation. Together, these findings demonstrate the existence of a nigro-striatal-amygdala circuit for conditioned fear memory formation and expression.
Topics: Mice; Animals; Dopamine; Acoustic Stimulation; Amygdala; Learning; Fear
PubMed: 37945595
DOI: 10.1038/s41467-023-43066-9 -
Cellular and Molecular Neurobiology Oct 2023The application of glial cell line-derive neurotrophic factor (GDNF) to cell cultures and animal models has demonstrated positive effects upon dopaminergic neuronal... (Review)
Review
The application of glial cell line-derive neurotrophic factor (GDNF) to cell cultures and animal models has demonstrated positive effects upon dopaminergic neuronal survival and development, function, restoration, and protection. On this basis, recombinant GDNF protein has been trialled in the treatment of late-stage human Parkinson's disease patients with only limited success that is likely due to a lack of viable receptor targets in an advanced state of neurodegeneration. The latest research points to more refined approaches of modulating GDNF signalling and an optimal quantity and spatial regulation of GDNF can be extrapolated using regulation of dopamine as a proxy measure. The basic research literature on dopaminergic effects of GDNF in animal models is reviewed, concluding that a twofold increase in natively expressing cells increases dopamine turnover and maximises neuroprotective and beneficial motor effects whilst minimising hyperdopaminergia and other side-effects. Methodological considerations for measurement of dopamine levels and neuroanatomical distinctions are made between populations of dopamine neurons and their respective effects upon movement and behaviour that will inform future research into this still-relevant growth factor.
Topics: Animals; Humans; Dopamine; Glial Cell Line-Derived Neurotrophic Factor; Substantia Nigra; Neuroglia; Parkinson Disease
PubMed: 37410316
DOI: 10.1007/s10571-023-01375-z -
Frontiers in Neuroendocrinology Oct 2023Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females,... (Review)
Review
Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.
Topics: Female; Humans; Male; Dopamine; Epigenesis, Genetic; Gonadal Steroid Hormones; Meta-Analysis as Topic; Progesterone; Sex Characteristics; Substance-Related Disorders; Systematic Reviews as Topic; Testosterone
PubMed: 37543184
DOI: 10.1016/j.yfrne.2023.101085 -
Nature Communications Nov 2023Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether...
Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice. We find that DGLα deletion from VTA dopamine neurons prevents depolarization-induced suppression of excitation (DSE), a form of 2-AG-mediated synaptic plasticity, in dopamine neurons. DGLα deletion also decreases effortful, cue-driven reward-seeking but has no effect on non-cued or low-effort operant tasks and other behaviors. Moreover, dopamine recording in the NAc reveals that deletion of DGLα impairs the transfer of accumbal dopamine signaling from a reward to its earliest predictors. These results demonstrate that 2-AG mobilization from VTA dopamine neurons is a necessary step for the generation of dopamine-based predictive associations that are required to direct and energize reward-oriented behavior.
Topics: Mice; Animals; Dopaminergic Neurons; Dopamine; Endocannabinoids; Ventral Tegmental Area; Reward
PubMed: 37985770
DOI: 10.1038/s41467-023-43131-3