Brain glucose hypometabolism is a prominent feature of Alzheimer's disease (AD), and in this case-control study we used Magnetic Resonance Spectroscopy (MRS) to assess AD-related differences in the posterior cingulate/precuneal ratio of glucose, lactate, and other metabolites.
Insulin resistance (IR) and type 2 diabetes are risk factors for Alzheimer's disease (AD). Exosomes are endosome-derived vesicles containing macromolecules reflecting their cellular source. Using a methodology for enriching blood exosomes for neuronal origin, we recently identified differentially phosphorylated forms of Insulin Receptor Substrate-1 (IRS-1), as in vivo biomarkers of brain-specific IR in AD (Kapogiannis et al., FASEB J, 2014). Here, we assess their cognitive, functional connectivity, and brain structure correlates in AD. In 26 patients with early AD (Global CDR 0.5 or 1), we isolated blood exosomes and enriched for neuronal origin by immunoabsorption with anti-L1CAM antibody. We measured concentrations of total IRS-1, total phosphorylated tyrosine (pY-), and phosphorylated Ser312 (pS312-) IRS-1. T1-weighted MPRAGE images were acquired and gray matter (GM) images were segmented using the VBM8 toolbox; voxel-based morphometry analysis against exosomal biomarkers was conducted in SPM8. The Allen Human Brain Atlas was used to create a GM mask of IRS-1 gene microarray expression values, which was used for Biological Parametric Mapping. Independent component analysis (ICA) with the GIFT toolbox was used to derive ventral, anterior and posterior default mode networks (DMNs) from resting EPI images (Fig.2A). Associations between DMNs and exosomal biomarkers were examined with the MANCOVAN toolbox. Higher pY-IRS-1 predicted worse global cognition, and immediate and delayed verbal memory. Higher pY-IRS-1 and pS312-IRS-1 were associated with less GM in lateral and medial temporal cortex, precuneus and medial prefrontal DMN nodes, before and after adjusting for IRS-1 expression (Fig.1). Higher pS312-IRS-1 was associated with lower low- to medium-frequency spectral power of anterior DMN (Fig.2.B.C.). Higher pY-IRS-1 was associated with higher low-frequency spectral power of anterior DMN, higher medium- to high-frequency spectral power of posterior and ventral DMN, and spatially restricted posterior DMN (Fig.2.D.E.F.G).
Abstract The effect of aging on motor learning is poorly understood. This study investigated response time and patterns of brain activation induced over the course of a bimanual motor learning task in three age groups. Twenty-two cognitively unimpaired participants (32%women) were grouped into Young (<35,n=6), Middle-Age (36-59,n=10), and Old (60+,n=6). A self-paced bimanual motor learning task was performed during fMRI. The task consisted of using 2 capital and 2 lower case letters in strings of 16 cues with 6 novel alternating with 6 repeated sequence blocks. To assess learning, a repeated measures ANOVA tested whether average time per slide differed over time between novel and sequence conditions. Voxel-wise changes in brain activation between novel and sequence conditions over time were examined using a within-subject repeated measures model. Faster initial time per slide was associated with younger age (p0.05). Old had increased brain activation in repeated sequence than novel conditions in right postcentral and superior parietal regions during the early half of the task compared to the second half (p0.05). We found behavioral evidence of motor learning in Middle-Age and Old, but not Young, perhaps because younger individuals performed quickly and learned sequence almost immediately. Among older individuals, sequence-specific learning in parietal regions challenges the view that it is mediated by only motor areas.
The global impact of COVID-19 driven by new variants may add to the negative mental health consequences of the prolonged pandemic, including posttraumatic stress symptoms (PTSS). University students may be prone to develop a series of PTSS due to life plan disruptions as well as increased uncertainty caused by the pandemic. The purpose of this study was to assess the associations between pandemic fatigue, anxiety sensitivity (AS), and PTSS among university students in South Korea.
Abstract Organophosphorus ( OP ) insecticides are pest‐control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well‐defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase ( AC hE), the enzyme that hydrolyzes the neurotransmitter acetylcholine ( AC h). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short‐ and long‐term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top‐selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms . image
Abstract Background Duchenne muscular dystrophy (DMD) is characterized clinically by severe, progressive loss of skeletal muscle. The phenotype is much less severe in the mdx mouse model of DMD than that seen in patients with DMD. However, a “critical period” has been described for the mdx mouse, during which there is a peak in muscle weakness and degeneration/regeneration between the 2 nd and 5 th weeks of life. A number of studies have employed small animal magnetic resonance imaging (MRI) to examine skeletal muscle in various dystrophic models, but such studies represent a snapshot in time rather than a longitudinal view. Results The in vivo cross-sectional T 2 -weighted image of the healthy (wild type, WT) muscles is homogeneously dark and this homogeneity does not change with time, as there is no disease. We, and others, have shown marked changes in MRI in dystrophic muscle, with multiple, unevenly distributed focal hyperintensities throughout the bulk of the muscles. Here we monitored an mdx mouse using MRI from 5 to 80 weeks of age. Temporal MRI scans show an increase in heterogeneity shortly after the critical period, at 9 and 13 weeks of age, with a decrease in heterogeneity thereafter. The 4.3-fold increase in percent heterogeneity at week 9 and 13 is consistent with the notion of an early critical period described for mdx mice. Conclusions Age is a significant variable in quantitative MR studies of the mdx mouse. The mdx mouse is typically studied during the critical period, at a time that most closely mimics the DMD pathology, but the preliminary findings here, albeit based on imaging only one mdx mouse over time, suggest that the changes in MRI can occur shortly after this period, when the muscles are still recovering.
