The cardinal motor symptoms of Parkinson's disease (PD) are caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Alpha‐synuclein (aSYN) pathology and mitochondrial ...dysfunction have been implicated in PD pathogenesis, but until recently it was unclear why SNc dopaminergic neurons should be particularly vulnerable to these two types of insult. In this brief review, the evidence that SNc dopaminergic neurons have an anatomical, physiological, and biochemical phenotype that predisposes them to mitochondrial dysfunction and synuclein pathology is summarized. The recognition that certain traits may predispose neurons to PD‐linked pathology creates translational opportunities for slowing or stopping disease progression.
This review summarizes evidence that selective neuronal vulnerability in Parkinson's disease results from several phenotypic traits: (a) calcium‐dependent, feed‐forward control of mitochondrial respiration leading to elevated reactive oxygen species and cytosolic calcium concentration; (b) an extensive axonal arbor; and (c) a reactive neurotransmitter. These traits increase vulnerability to genetic mutations associated with PD, age and environmental toxins.
Human and non-human animal behavior is highly malleable and adapts successfully to internal and external demands. Such behavioral success stands in striking contrast to the apparent instability in ...neural activity (i.e., variability) from which it arises. Here, we summon the considerable evidence across scales, species, and imaging modalities that neural variability represents a key, undervalued dimension for understanding brain-behavior relationships at inter- and intra-individual levels. We believe that only by incorporating a specific focus on variability will the neural foundation of behavior be comprehensively understood.
Successful behavior arises from brain activity exhibiting remarkable variability. Summoning evidence across species, scales, and techniques, Waschke et al. argue that neural variability represents a key, undervalued dimension essential for understanding inter- and intra-individual associations between brain and behavior.
A cerium metal organic framework-loaded silver nanocluster (MOFCeAgNC) is synthesized by a facile stirring procedure with trimesic acid, cerium nitrate, silver nitrate and NaBH4, which exhibites ...strong catalytic activity in the indicated reaction of HAuCl4-sodium lactate (SL). MOFCeAgNC can sensitively detect dopamine (DA) by surface-enhanced Raman scattering (SERS) and resonance Rayleigh scattering (RRS) techniques with a detection concentration range of 0.01–0.25 nmol/L and a detection limit of 0.008 nmol/L. Based on the specific binding of aptamer (Apt)-DA and the catalytic amplification strategy of MOFCeAgNC on HAuCl4-SL, a sensitive and convenient DA platform for dual-mode detection of SERS and RRS is constructed. In addition, the platform is successfully applied to detect DA in human serum with satisfactory recoveries (95.7–102%).
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•A novel stable and highly catalytic MOFCeAgNC nanosol was prepared.•MOFCeAgNC had a strong catalytic effect on the HAuCl4-SL indicator reaction.•The SERS/RRS dual-mode detection method was constructed based on the reaction of aptamer and indicator.•The aptamer detection of DA was label-free, sensitive, and selective.
Delay discounting refers to the depreciation of the value of a reward as a function of the time it takes to obtain it. Growing evidence shows altered delay discounting in several pathological ...conditions, including neurological disorders. Here, we conducted a systematic review and meta-analysis of the published literature on delay discounting (DD) in Parkinson’s Disease (PD). We found steeper DD in patients with PD, compared to healthy controls, both in “on” and “off” dopaminergic medication. These results confirm altered DD in PD and suggest an independent influence of the dopaminergic medication and the clinical condition itself on it. Also the effect of impulse control disorder and of pharmacological treatments are analysed.
•We explored delay discounting in Parkinson disease.•Patients with Parkinson disease (PD) show steeper delay discounting than healthy controls.•Medicated patients with PD show steeper delay discounting than non-medicated ones.•Dopaminergic medication and diagnosis of PD have an independent influence on delay discounting.
Einwandige Kohlenstoffnanoröhren (single‐walled carbon nanotubes, SWCNTs) sind vielseitig einsetzbare Bausteine für Biosensoren, die im nahen Infrarot (NIR) fluoreszieren. Ihre Oberfläche kann ...chemisch so modifiziert werden, dass sie auf Analyten mit einer Veränderung ihrer Fluoreszenz reagieren. Intensitätsbasierte Signale werden jedoch leicht durch äußere Faktoren wie Bewegungen der Probe beeinflusst. Hier zeigen wir Fluoreszenz‐Lebensdauer Mikroskopie (fluorescence lifetime imaging microscopy, FLIM) von SWCNT‐basierten Sensoren im NIR. Dafür wurde ein konfokales Laser‐Scanning‐Mikroskop (CLSM) für NIR‐Signale (>800 nm) angepasst und zeitkorrelierte Einzelphotonenzählung von (GT)10‐DNA‐funktionalisierten SWCNTs verwendet. (GT)10‐SWCNTs fungieren als Sensoren für den wichtigen Neurotransmitter Dopamin. Ihre Fluoreszenzlebensdauer (>900 nm) fällt biexponentiell ab, wobei die längere Lebensdauerkomponente (370 ps) mit steigender Dopaminkonzentration um bis zu 25 % ansteigt. Mit diesen Sensoren können Zellen beschichtet werden, um extrazelluläres Dopamin in 3D mittels FLIM zu messen. Wir demonstrieren damit das Potenzial der Fluoreszenzlebensdauer als Messgröße für SWCNT‐basierte NIR‐Sensoren.
DNA‐funktionalisierte einwandige Kohlenstoffnanoröhren (single‐walled carbon nanotubes, SWCNTs) dienen als fluoreszente Sensoren im Nahinfrarot für den Neurotransmitter Dopamin. Diese Sensoren ändern ihre Fluoreszenzlebensdauer, die durch gepulste Anregung und Einzelphotonenzählung quantifiziert werden kann. Die Lebenszeiten reagieren empfindlich auf unterschiedliche Dopaminkonzentrationen, was für die Darstellung der Dopaminfreisetzung durch Zellen genutzt wird.
Background and Aim: Zingiber officinale (ginger) extract increased dopamine concentration in various brain areas. Therefore, the present study aimed to investigate how ginger extract can affect the ...efficiency of D2 receptor agonist (bromocriptine) and antagonist (chlorpromazine) on pain sensitivity in rats. Materials and Methods: Forty-eight adult male rats in standard conditions divided into eight groups, i.e. the control, the ginger sham1, sham2, ginger, bromocriptine 10 or 30 µM + ginger, and chlorpromazine 20 or 40 µM + ginger. The cannulation of the lateral ventricle was conducted unilaterally by the stereotaxic procedure. A pain sensitivity test was carried out in all the groups by formalin test on the 16th day. Results: The results of this study indicated that ginger could remarkablly (P<0.01) reduce pain sensitivity in all stages of the formalin test. As the data revealed, bromocriptine 10 or 30 µg/rat and chlorpromazine 20 or 40 µg/rat significantly (P<0.01) decreased the pain sensitivity in all phases of the formalin test in comparison with the control and sham groups. However, chlorpromazine 20 or 40 µg/rat noticeably (P<0.01) increased the pain sensitivity when compared to ginger and bromocriptine groups. Conclusion: According to the results of the present study, ginger mimics the analgesic effect of bromocriptine. Moreover, ginger has attenuated the hyperalgesic effect of chlorpromazine. It seems that ginger has a synergistic effect with the analgesic effect of the dopamine D2 receptor.
The current review is an update on experimental approaches in which birds serve as model species for the investigation of typical failure symptoms associated with autism spectrum disorder (ASD). The ...discussion is focused on deficiencies of social behavior, from social interactions of domestic chicks, based on visual and auditory cues, to vocal communication in songbirds. Two groups of pathogenetic/risk factors are discussed: 1) non-genetic (environmental/epigenetic) factors, exemplified by embryonic exposure to valproic acid (VPA), and 2) genetic factors, represented by a list of candidate genes and signaling pathways of diagnostic or predictive value in ASD patients. Given the similarities of birds as experimental models to humans (visual orientation, vocal learning, social cohesions), avian models usefully contribute toward the elucidation of the neural systems and developmental factors underlying ASD, improving the applicability of preclinical results obtained on laboratory rodents. Furthermore, they may predict potential susceptibility factors worthy of investigation (both by animal studies and by monitoring human babies at risk), with potential therapeutic consequence.
Recent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of prediction errors plays a key role in learning and ...decision-making, is controlled by dopamine and contributes to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation with a placebo, a dopamine receptor agonist bromocriptine or a dopamine receptor antagonist sulpiride (dopamine study n = 59) and in patients with early psychosis (psychosis study n = 74: 20 participants with first-episode psychosis, 30 healthy controls and 24 participants with at-risk mental state attenuated psychotic symptoms). Behavioural computational modelling indicated that precision weighting of prediction errors benefits learning in health and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors, which signal surprise, relative to their precision in superior frontal cortex (replicated across studies, combined n = 133), which was perturbed by dopaminergic modulation, impaired in psychosis and associated with task performance and schizotypy (schizotypy correlation in 86 healthy volunteers). In contrast to our previous work, we did not observe significant precision-weighting of signed prediction errors, which signal valence, in the midbrain and ventral striatum in the healthy controls (or patients) in the psychosis study. We conclude that healthy people, but not patients with first-episode psychosis, take into account the precision of the environment when updating beliefs. Precision weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.
Abstract
Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory performance entails ...brain-wide switching between activity states using a combination of functional magnetic resonance imaging in healthy controls and individuals with schizophrenia, pharmacological fMRI, genetic analyses and network control theory. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Individuals with schizophrenia show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations. Our results demonstrate the relevance of dopamine signaling for the steering of whole-brain network dynamics during working memory and link these processes to schizophrenia pathophysiology.
A new surface bioconjugation strategy is presented. A polydopamine surface coating provides chemical activation on material surfaces, is resistant to hydrolysis, and offers selectivity in coupling of ...biomolecules via nucleophilic groups through simple pH control. Control of orientation of immobilized biomolecules may be possible using terminally modified DNA or His‐containing proteins.
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