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Stage II trial of natalizumab for the anti-Hu connected paraneoplastic nerve syndromes.
We found that the brain structural network continues to strengthen during later adolescence and adulthood, through the first 20-30 years of life. Older adults, aged 65-75, had a significantly less optimized topological organization in their structural network, with decreased global efficiency and increased path lengths versus subjects in other groups. This study suggests that probabilistic tractography based on EAP provides a reliable method to construct macroscale structural connectivity networks to capture the age-associated changes of brain structures. click here Copyright © 2020 Wu, Peng, Selvaraj, Schulz and Zhang.Patients with Parkinson's disease (PD) generally have reduced risk of developing many types of cancers, except melanoma-a malignant tumor of melanin-producing cells in the skin. For decades, a large number of epidemiological studies have reported that the occurrence of melanoma is higher than expected among subjects with PD, and the occurrence of PD is reciprocally higher than expected among patients with melanoma. More recent epidemiological studies further indicated a bidirectional association, not only in the patients themselves but also in their relatives. This association between PD and melanoma offers a unique opportunity to understand PD. Here, we summarize epidemiological, clinical, and biological evidence in regard to shared risk factors and possible underlying mechanisms for these two seemingly distinct conditions. Copyright © 2020 Ye, Wen, Al-Kuwari and Chen.Alzheimer's disease (AD) is the most common form of dementia worldwide. It is mostly known for its devastating effect on memory and learning but behavioral alterations commonly known as neuropsychiatric disturbances (NPDs) are also characteristics of the disease. These include apathy, depression-like behavior, and sleep disturbances, and they all contribute to an increased caregiver burden and earlier institutionalization. The interaction between NPDs and AD pathology is not well understood, but the consensus is that they contribute to disease progression and faster decline. Consequently, recognizing and treating NPDs might improve AD pathology and increase the quality of life for both patients and caregivers. In this review article, we examine previous and current literature on apathy, depressive symptoms, and sleep disturbances in AD patients and preclinical AD mechanistic models. We hypothesize that tau accumulation, beta-amyloid (Aβ) aggregation, neuroinflammation, mitochondrial damage, and loss of the locus coeruleus (LC)-norepinephrine (NE) system all collectively impact the development of NPDs and contribute synergistically to AD pathology. Targeting more than one of these processes might provide the most optimal strategy for treating NPDs and AD. The development of such clinical approaches would be preceded by preclinical studies, for which robust and reliable mechanistic models of NPD-like behavior are needed. Thus, developing effective preclinical research models represents an important step towards a better understanding of NPDs in AD. Copyright © 2020 Clement, Wiborg and Asuni.Introduction Evidence suggests urinary urgency is associated with cognitive impairment in a subtype of Parkinson's disease (PD) patients. This study investigates if cognitive impairment independently predicts the presence of urinary dysfunction. Methods We report data of 189 idiopathic PD patients, excluding those with concomitant diseases or medication interacting with bladder function. A standardized questionnaire was used to define the presence of urinary urgency. All patients underwent a comprehensive motor, cognitive non-motor and health-related quality of life (HRQoL) assessment. Multivariable linear regression analysis was performed to identify independent variables characterizing urinary urgency in PD (PD-UU), which were assigned as discriminant features to estimate their individual contribution to the phenotype of the PD-UU group. Results Of 189 PD patients, 115 (60.8%) reported PD-UU. The linear regression analysis showed that among cognitive domains, executive function (EF; p = 0.04) had a significpelt-Scarfone.Limb remote ischemic preconditioning (RIPC) has been proven to alleviate stroke injury in young rats, but its protective effect and its mechanism in aged rats are still unclear. Hypoxia-inducible factor (HIF) is one of the important markers of stroke, and its high expression plays an important role in the pathogenesis of stroke. In this study, we tested the hypothesis that RIPC could regulate the expression of HIF, leading to reduced inflammatory responses in aged rats. Stroke was induced by transient middle cerebral artery occlusion (MCAo) in aged rats, and RIPC was conducted in both hind limbs. The HIF-1α and HIF-2α mRNA and protein were examined by real-time RT-PCR and western blotting (WB). Inflammatory cytokines in the peripheral blood and brain were measured using AimPlex multiplex immunoassays. The protein levels of p-Akt, Akt, p-ERK, and ERK were examined by WB. We investigated that RIPC reduced the infarct size, improved neurological functions, and decreased the expression of HIF-1α and HIF-2α in the ischemic brain. RIPC reduced the levels of IL-1β, IL-6 and IFN-γ in the peripheral blood and the levels of IL-1β and IFN-γ in the ischemic brain 48 h post-stroke. Moreover, intraperitoneal injection of the HIF inhibitor, acriflavine hydrochloride (ACF), abolished the protection of RIPC with respect to infarct size and neurological functions and neutralized the downregulation of pro-inflammatory IL-1β, IL-6 and IFN-γ. ACF also reversed the activation of the Akt signaling pathway induced by RIPC following stroke. HIF may play a key role in RIPC, which was likely mediated by the Akt signaling pathway and systemic modulation of the inflammatory response in aged rats. Copyright © 2020 Du, Yang, Liu, Wang, Zhang, Zhao, Du and Geng.Aim Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. Methods We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. Results The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, P less then 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, P less then 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides, hsCRP was negatively correlated with MoCA; while total cholesterol, HDL-C and LDL-C were positively correlated with the MoCA, respectively. Conclusion Our findings suggest that lower SOD along with cholesterol, HDL-C and LDL-C, and higher hsCRP levels might be important markers to assess the PD severity. A better understanding of SOD and hsCRP may yield insights into the pathogenesis of PD. Copyright © 2020 Yang, Chang, Que, Weng, Deng, Wang, Huang, Xie, Wei, Yang, Li, Ma, Zhou, Tang, Mok, Zhu and Wang.Human brain evolution toward complexity has been achieved with increasing energy supply as the main adaptation in brain metabolism. Energy metabolism, like other biochemical reactions in aerobic cells, is under enzymatic control and strictly regulated. Nevertheless, physiologically uncontrolled and deleterious reactions take place. It has been proposed that these reactions constitute the basic molecular mechanisms that underlie the maintenance or loss-of-function of neurons and, by extension, cerebral functions during brain aging. In this review article, we focus attention on the role of the nonenzymatic and irreversible adduction of fumarate to the protein thiols, which leads to the formation of S-(2-succino)cysteine (2SC; protein succination) in the human brain. In particular, we first offer a brief approach to the succination reaction, features related to the specificity of protein succination, methods for their detection and quantification, the bases for considering 2SC as a biomarker of mitochondrial stress, the succinated proteome, the cross-regional differences in 2SC content, and changes during brain aging, as well as the potential regulatory significance of fumarate and 2SC. We propose that 2SC defines cross-regional differences of metabolic mitochondrial stress in the human brain and that mitochondrial stress is sustained throughout the healthy adult lifespan in order to preserve neuronal function and survival. Copyright © 2020 Jové, Pradas, Mota-Martorell, Cabré, Ayala, Ferrer and Pamplona.The association between physical fitness and cognitive performance has been widely investigated in the literature. However, the neurophysiological mechanisms underlying this relationship are not yet clear. Here, we aim to evaluate the interactions between executive function measures, heart rate variability (HRV), and physical fitness in the context of the neurovisceral integration (NVI) theory. Twenty-eight healthy elderly subjects (>60 years) were submitted to evaluation of executive performance with three computerized tests the N-back test measured working memory capacity, the Stroop Color test evaluated inhibitory control and selective attention, and the Wisconsin Card Sorting Test (WCST) evaluated abstract reasoning and cognitive flexibility. We also used the Physical Testing Battery for the Elderly to measure aerobic capacity, dynamic balance, upper body flexibility, and handgrip strength. Our results confirm the relationship between executive function and physical fitness, particularly between working memory, cardiorespiratory fitness, and dynamic balance. We also demonstrate an association between executive performance and HRV in older people, corroborating previous results from other groups obtained in young adults. However, our regression models did not indicate that HRV mediates the relationship between cognition and physical fitness in the elderly, suggesting that age-related degeneration of autonomic control can affect aspects of NVI in this population. Copyright © 2020 Matos, Vido, Garcia, Lopes and Pereira.Normative aging is known to affect how decisions are made in risky situations. Although important individual variability exists, on average, aging is accompanied by greater risk aversion. Here the behavioral and neural mechanisms of greater risk aversion were examined in young and old rats trained on an instrumental probability discounting task. Consistent with the literature, old rats showed greater discounting of reward value when the probability of obtaining rewards dropped below 100%. Behaviorally, reward magnitude discrimination was the same between young and old rats, and yet these same rats exhibited reduced sensitivity to positive, but not negative, choice outcomes. The latter behavioral result was congruent with additional findings that the aged ventral tegmental neurons (including dopamine cells) were less responsive to rewards when compared to the same cell types recorded from young animals. In sum, it appears that reduced responses of dopamine neurons to rewards contribute to aging-related changes in risky decisions.
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