bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine D4 receptor modulates inhibitory transmission in pallido‐pallidal terminals and regulates motor behavior
Authors: Conde Rojas Israel , Acosta‐García Jackeline , Caballero‐Florán Rene Nahum , Jijón‐Lorenzo Rafael , Recillas‐Morales Sergio , Avalos‐Fuentes José Arturo , Paz‐Bermúdez Francisco , Leyva‐Gómez Gerardo , Cortés Hernán , Florán Benjamín 
Published: October 2020

AbstractTwo major groups of terminals release GABA within the Globus pallidus; one group is constituted by projections from striatal neurons, while endings of the intranuclear collaterals form the other one. Each neurons' population expresses different subtypes of dopamine D2‐like receptors: D2R subtype is expressed by encephalin‐positive MSNs, while pallidal neurons express the D4R subtype. The D2R modulates the firing rate of striatal neurons and GABA release at their projection areas, while the D4R regulates Globus pallidus neurons excitability and GABA release at their projection areas. However, it is unknown if these receptors control GABA release at pallido‐pallidal collaterals and regulate motor behavior. Here, we present neurochemical evidence of protein content and binding of D4R in pallidal synaptosomes, control of [3H] GABA release in pallidal slices of rat, electrophysiological evidence of the presence of D4R on pallidal recurrent collaterals in mouse slices, and turning behavior induced by D4R antagonist microinjected in amphetamine challenged rats. As in projection areas of pallidal neurons, GABAergic transmission in pallido‐pallidal recurrent synapses is under modulation of D4R, while the D2R subtype, as known, modulates striato‐pallidal projections. Also, as in projection areas, D4R contributes to control the motor activity differently than D2R. This study could help to understand the organization of intra‐pallidal circuitry.
Short‐term exposure to the simple polyphenolic compound gallic acid induces neuronal hyperactivity in zebrafish larvae
Authors: Annona Giovanni , Tarallo Andrea , Nittoli Valeria , Varricchio Ettore , Sordino Paolo , D'Aniello Salvatore , Paolucci Marina 
Published: October 2020

AbstractA growing body of evidence suggests that the biological effects of polyphenols are not restricted to antioxidant activity, but they exert a wide range of modulatory effects on metabolic pathways, cellular signaling and gene expression. In this study, we tested the minimum safe concentration of gallic acid (GA) in 72 hpf zebrafish larvae in order to evaluate the effects on the central nervous system and the behavioral response. We showed that a short exposure (30 min) induces the depletion of the two main excitatory and inhibitory neurotransmitters, Glu and GABA, respectively, in the larval nervous system. The acute impairment of GABAergic‐glutamatergic balance was paralleled by an increase of thefosabneuronal activity marker in specific brain areas, such as the forebrain, olfactory bulbs, pallial area, ventral midbrain, tegmentum, and the medulla oblongata ventral area. The neuronal excitation was mirrored by the increased cumulative motor response. The inhibition of the olfactory epithelium with brief cadmium exposition suggests a direct involvement of olfaction in the larvae response to GA. Our results demonstrate that a brief exposure to GA induces motoneuronal hyperexcitability in zebrafish. The behavioral response was probably elicited through the activation of an odorous, or chemical, stimulus. The specificity of the activated neuronal territories suggests the involvement of additional signaling pathways. Although the underlying molecular mechanisms remain to be elucidated, our data support the hypothesis that GA acts as an excitatory molecule, capable of inducing a specific nerve response. These results offer a new vision on potential effects of GA.
Nonpharmacological interventions for respiratory health in Parkinson’s disease: A systematic review and meta‐analysis
Authors: McMahon L. , Blake C. , Lennon O. 
Published: October 2020

Background and purposeRespiratory dysfunction in Parkinson’s disease (PD) is often an underdiagnosed and untreated impairment associated with the disease. Clinically, a reactive approach to respiratory morbidity is taken, rather than preventative approaches that address underlying impairment/s. This systematic review identifies the current evidence to support nonpharmacological interventions to improve respiratory impairments in individuals with PD.MethodsThe relevant literature was searched using a customised and systematic strategy. Randomised and nonrandomised control trials of nonpharmacological interventions targeting respiratory outcome measures in PD were included. Outcomes of interest were respiratory morbidity and mortality, respiratory muscle strength, spirometry measures, lung volumes, peak cough flow, and perception of dyspnoea.ResultsNonpharmacological interventions included: functional training, generalised strength training, respiratory muscle strength training, aerobic exercise, qigong, yoga, breath stacking, incentive spirometry and singing. Methodological quality of included studies varied. Meta‐analyses of nonpharmacological interventions demonstrated significant effects for inspiratory muscle strength (mean difference [MD] 19.68; confidence interval [CI] 8.49, 30.87; z = 3.45; p = 0.0006; I2 = 2%), expiratory muscle strength (MD 18.97; CI 7.79, 30.14; z = 3.33; p = 0.0009; I2 = 23%) and peak expiratory flow (MD 72.21; CI 31.19, 113.24; z = 3.45; p = 0.0006; I2 = 0%). Best‐evidence synthesis identified level 1 evidence supporting nonpharmacological interventions for improving peak cough flow and perceived dyspnoea. No studies were identified reporting outcomes of respiratory rate, inspiration:expiration ratio or respiratory morbidity or mortality in PD.ConclusionsNonpharmacological interventions improved respiratory muscle strength and peak expiratory flow in PD. Additional trials targeting respiratory dysfunction and longitudinal studies examining the relationship between respiratory dysfunction and morbidity and mortality rates in PD are required.
Associations between texture of T1‐weighted magnetic resonance imaging and radiographic pathologies in Alzheimer’s disease
Authors: Lee Subin , Kim Ki Woong ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2020

AbstractBackground and purposeTexture analysis of magnetic resonance imaging (MRI) brain scans have been proposed as a promising tool in the early diagnosis of Alzheimer’s disease (AD), but its biological correlates remain unknown. In this study, we examined the relationship between MRI texture features and AD pathology.MethodsThe study included 150 participants who had a 3.0T T1‐weighted image, amyloid‐β positron emission tomography (PET), and tau PET within 3 months of each other. In each of six brain regions (hippocampus, precuneus, and entorhinal, middle temporal, posterior cingulate and superior frontal cortices), linear regression analyses adjusting for age and sex was performed to examine the effects of regional amyloid‐β and tau burden on regional texture features. We also compared neuroimaging measures based on pathological severity using ANOVA.ResultsIn all regions, tau burden (p < 0.05), but not amyloid‐β burden, were associated with a certain texture feature that varied with the region’s cytoarchitecture. Specifically, autocorrelation and cluster shade were associated with tau burden in allocortical and periallocortical regions, whereas entropy and contrast were associated with tau burden in neocortical regions. Mean signal intensity of each region did not show any associations with AD pathology. The values of the region‐specific textures also varied across groups of varying pathological severity.ConclusionsOur results suggest that textures of T1‐weighted MRI reflect changes in the brain that are associated with regional tau burden and the local cytoarchitecture. This study provides insight into how MRI texture can be used for detection of microstructural changes in AD.
Association between cortical microinfarcts and total small vessel disease burden in cerebral amyloid angiopathy on 3‐Tesla magnetic resonance imaging
Authors: Ii Yuichiro , Ishikawa Hidehiro , Shindo Akihiro , Matsuyama Hirofumi , Matsuura Keita , Matsuda Kana , Yoshimaru Kimiko , Satoh Masayuki , Kogue Ryota , Umino Maki , Maeda Masayuki , Tomimoto Hidekazu 
Published: October 2020

AbstractBackground and purposeCortical microinfarcts (CMIs) are frequently found in the brains of patients with advanced cerebral amyloid angiopathy (CAA) at autopsy. The small vessel disease (SVD) score for CAA (i.e., the CAA‐SVD score) has been proposed to evaluate the severity of CAA‐associated vasculopathic changes by a combination of magnetic resonance imaging (MRI) markers. The aim of this study was to examine the association between total CAA‐SVD score and features of CMIs on in vivo 3‐Tesla MRI.MethodsEighty patients with probable CAA were retrospectively analyzed. Lobar cerebral microbleeds, cortical superficial siderosis, enlargement of perivascular space in the centrum semiovale and white matter hyperintensity were collectively assessed, and the total CAA‐SVD score was calculated. The presence of CMI was also examined.ResultsOf the 80 patients, 13 (16.25%) had CMIs. CMIs were detected more frequently in the parietal and occipital lobes. A positive correlation was found between total CAA‐SVD score and prevalence of CMI (ρ = 0.943; p = 0.005). Total CAA‐SVD score was significantly higher in patients with CMIs than in those without (p = 0.009). In a multivariable logistic regression analysis, the presence of CMIs was significantly associated with total CAA‐SVD score (odds ratio 2.318 [95% confidence interval 1.228–4.376]; p = 0.01, per each additional point).ConclusionsThe presence of CMIs with a high CAA‐SVD score could be an indicator of more severe amyloid‐associated vasculopathic changes in patients with probable CAA.
Spinal dural leaks in patients with infratentorial superficial siderosis of the central nervous system—Refinement of a diagnostic algorithm
Authors: Friedauer Lucie , Rezny‐Kasprzak Beata , Steinmetz Helmuth , du Mesnil de Rochemont Richard , Foerch Christian 
Published: October 2020

AbstractBackground and purposeSuperficial siderosis of the central nervous system is a sporadic finding in magnetic resonance imaging, resulting from recurrent bleedings into the subarachnoid space. This study aimed to determine the frequency of spinal dural cerebrospinal fluid (CSF) leaks amongst patients with a symmetric infratentorial siderosis pattern.MethodsIn all, 97,733 magnetic resonance images performed between 2007 and 2018 in our neurocenter were screened by a keyword search for “hemosiderosis” and “superficial siderosis.” Siderosis patterns on brain imaging were classified according to a previously published algorithm. Potential causative intracranial bleeding events were also assessed. Patients with a symmetric infratentorial siderosis pattern but without causative intracranial bleeding events in history were prospectively evaluated for spinal pathologies.ResultsForty‐two patients with isolated supratentorial siderosis, 30 with symmetric infratentorial siderosis and 21 with limited (non‐symmetric) infratentorial siderosis were identified. Amyloid angiopathy and subarachnoid hemorrhage were causes for isolated supratentorial siderosis. In all four patients with a symmetric infratentorial siderosis pattern but without a causative intracranial bleeding event in history, spinal dural abnormalities were detected. Dural leaks were searched for in patients with symmetric infratentorial siderosis and a history of intracranial bleeding event without known bleeding etiology, considering that spinal dural CSF leaks themselves may also cause intracranial hemorrhage, for example by inducing venous thrombosis due to low CSF pressure. Thereby, one additional spinal dural leak was detected.ConclusionsPersisting spinal dural CSF leaks can frequently be identified in patients with a symmetric infratentorial siderosis pattern. Diagnostic workup in these cases should include magnetic resonance imaging of the whole spine.
Atipamezole, a specific α2A antagonist, suppresses spike‐and‐wave discharges and alters Ca2⁺/calmodulin‐dependent protein kinase II in the thalamus of genetic absence epilepsy rats
Authors: Yavuz Melis , Aydın Banu , Çarçak Nihan , Akman Özlem , Raci Yananlı Hasan , Onat Filiz 
Published: October 2020

AbstractObjectiveThe role of α2A adrenergic receptors (α2AARs) in absence epilepsy is not well characterized. Therefore, we investigated the outcomes of the specific antagonism of α2AARs on the spike‐and‐wave discharges (SWDs) in genetic absence epilepsy rats from Strasbourg (GAERSs), together with its influence on the behavior and second messenger systems, which may point to the mechanisms to which a possible SWD modulation can be related.MethodsAtipamezole, an α2AAR antagonist, was administered intracerebroventricularly to the adult GAERSs, and electroencephalography (EEG) was conducted. The cumulative duration and number of SWDs, and the mean duration of each SWD complex were counted. The relative power of the EEG frequency bands and behavioral activity after the acute application of two doses (12 and 31 μg/5 μL) of atipamezole were evaluated. The levels of cyclic adenosine monophosphate and calcium/calmodulin‐dependent kinase II (CaMKII) were measured in the cortex, thalamus, and hippocampus of naive Wistar rats and GAERSs, administered with artificial cerebrospinal fluid (aCSF) as a vehicle, or either acute or chronic atipamezole (12 μg), the latter being administered for 5 consecutive days.ResultsAtipamezole significantly suppressed SWDs dose‐dependently, without affecting the relative power values of EEG frequency spectrum. The stereotypic activity was significantly lower in both naive Wistar rats and GAERSs receiving the highest dose (31 μg) of atipamezole compared to GAERSs receiving aCSF. In GAERSs, CaMKII levels were found to be higher in the thalamus after the acute and chronic application of SWD‐suppressing doses of atipamezole (12 and 31 μg) compared to aCSF.SignificanceThis study emphasizes the α2AR‐related modulation of absence epilepsy and particularly the significance of α2AR antagonism in suppressing SWDs. Atipamezole's SWD‐suppressive actions may be through CaMKII‐mediated second messenger systems in the thalamus.
Neonatal genetic epilepsies display convergent white matter microstructural abnormalities
Authors: Sandoval Karamian Amanda G. , Wusthoff Courtney J. , Boothroyd Derek , Yeom Kristen W. , Knowles Juliet K. 
Published: October 2020

AbstractWhite matter undergoes rapid development in the neonatal period. Its structure during and after development is influenced by neuronal activity. Pathological neuronal activity, as in seizures, might alter white matter, which in turn may contribute to network dysfunction. Neonatal epilepsy presents an opportunity to investigate seizures and early white matter development. Our objective was to determine whether neonatal seizures in the absence of brain injury or congenital anomalies are associated with altered white matter microstructure. In this retrospective case‐control study of term neonates, cases had confirmed or suspected genetic epilepsy and normal brain magnetic resonance imaging (MRI) and no other conditions independently impacting white matter. Controls were healthy neonates with normal MRI results. White matter microstructure was assessed via quantitative mean diffusivity (MD). In 22 cases, MD was significantly lower in the genu of the corpus callosum, compared to 22 controls, controlling for gestational age and postmenstrual age at MRI. This finding suggests convergent abnormal corpus callosum microstructure in neonatal epilepsies with diverse suspected genetic causes. Further study is needed to determine the specific nature, causes, and functional impact of seizure‐associated abnormal white matter in neonates, a potential pathogenic mechanism.
Insecticide exposure affects intergenerational patterns of DNA methylation in the Colorado potato beetle, Leptinotarsa decemlineata
Authors: Brevik Kristian , Bueno Erika M. , McKay Stephanie , Schoville Sean D. , Chen Yolanda H. 
Published: October 2020

AbstractInsecticide use is pervasive as a selective force in modern agroecosystems. Insect herbivores exposed to these insecticides have been able to rapidly evolve resistance to them, but how they are able to do so is poorly understood. One possible but largely unexplored explanation is that exposure to sublethal doses of insecticides may alter epigenetic patterns that are heritable. For instance, epigenetic mechanisms, such as DNA methylation that modifies gene expression without changing the underlying genetic code, may facilitate the emergence of resistant phenotypes in complex ways. We assessed the effects of sublethal insecticide exposure, with the neonicotinoid imidacloprid, on DNA methylation in the Colorado potato beetle, Leptinotarsa decemlineata, examining both global changes in DNA methylation and specific changes found within genes and transposable elements. We found that exposure to insecticide led to decreases in global DNA methylation for parent and F2 generations and that many of the sites of changes in methylation are found within genes associated with insecticide resistance, such as cytochrome P450s, or within transposable elements. Exposure to sublethal doses of insecticide caused heritable changes in DNA methylation in an agricultural insect herbivore. Therefore, epigenetics may play a role in insecticide resistance, highlighting a fundamental mechanism of evolution while informing how we might better coexist with insect species in agroecosystems.
Genetic mixing for population management: From genetic rescue to provenancing
Authors: Hoffmann Ary A. , Miller Adam D. , Weeks Andrew R. 
Published: October 2020

AbstractAnimal and plant species around the world are being challenged by the deleterious effects of inbreeding, loss of genetic diversity, and maladaptation due to widespread habitat destruction and rapid climate change. In many cases, interventions will likely be needed to safeguard populations and species and to maintain functioning ecosystems. Strategies aimed at initiating, reinstating, or enhancing patterns of gene flow via the deliberate movement of genotypes around the environment are generating growing interest with broad applications in conservation and environmental management. These diverse strategies go by various names ranging from genetic or evolutionary rescue to provenancing and genetic resurrection. Our aim here is to provide some clarification around terminology and to how these strategies are connected and linked to underlying genetic processes. We draw on case studies from the literature and outline mechanisms that underlie how the various strategies aim to increase species fitness and impact the wider community. We argue that understanding mechanisms leading to species decline and community impact is a key to successful implementation of these strategies. We emphasize the need to consider the nature of source and recipient populations, as well as associated risks and trade‐offs for the various strategies. This overview highlights where strategies are likely to have potential at population, species, and ecosystem scales, but also where they should probably not be attempted depending on the overall aims of the intervention. We advocate an approach where short‐ and long‐term strategies are integrated into a decision framework that also considers nongenetic aspects of management.
The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid‐related bioactivity over retinol and retinyl palmitate in human skin models
Authors: Bjerke Donald L. , Li Rui , Price Jason M. , Dobson Roy L. M. , Rodrigues MyriamRubecca , Tey ChingSiang , Vires Laura , Adams Rachel L. , Sherrill Joseph D. , Styczynski Peter B. , Goncalves Kirsty , Maltman Victoria , Przyborski Stefan , Oblong John E. 
Published: October 2020

AbstractHuman skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids using in vitro and ex vivo skin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67 and filaggrin. A retinoic acid receptor‐alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results from ex vivo skin found that RP and ROL have higher penetration levels compared with RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14‐hydroxy‐4,14‐retro‐retinol (14‐HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm.
Absence of ethnic difference on single‐dose pharmacokinetics of rivoceranib between healthy male Caucasian, Japanese, and Chinese subjects
Authors: Sachar Madhav , Park Cheol Hee , Pesco‐Koplowitz Luana , Koplowitz Barry , McGinn Arlo 
Published: October 2020

AbstractRivoceranib (known in China as apatinib) is a selective vascular endothelial growth factor receptor‐2 (VEGFR‐2) tyrosine kinase inhibitor which inhibits angiogenesis in solid tumors. The aim of study was to evaluate potential pharmacokinetic (PK) differences between the Caucasian, Japanese, and Chinese populations. An open‐label, single‐dose, parallel‐design PK study of rivoceranib was conducted in Caucasian, Japanese, and Chinese subjects. A total of 18 healthy males were recruited to each group (54 total), and 201 mg rivoceranib tablets (as 250 mg rivoceranib mesylate) were administered orally to subjects. Plasma samples were collected, and rivoceranib plasma concentration was determined using LC‐MS/MS. For PK analysis, non‐compartmental and compartmental analyses were performed. Intrinsic factors (CYP2C19 and CYP3A4 genotype) were also examined. Non‐compartmental analysis showed no significant difference in AUC0–t, AUC0–∞, Cmax, tmax, and t1⁄2. Apparent clearance and volume of distribution were different across the three populations; however, the extent of this difference does not require dose modification. For compartmental modeling, a two‐compartment model was used to fit the plasma concentrations. No significant difference was observed in absorption, elimination, and intercompartmental transfer rate constants among the three groups. The present study shows no major ethnic PK differences between Caucasian, Japanese, and Chinese populations.