Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs.
View Article and Find Full Text PDFThis article describes the development and validation of a shortened form of SELweb EE, a web-based assessment for social-emotional skills in the early elementary grades. Using a Rasch approach, in the first study, we used data from two archival data sets to reduce the number of items in three subtests to create short forms that maintained item fit, item difficulty, item discrimination, and test information function range. In the second study, we created and administered a short form of SELweb EE to a demographically diverse cross-validation sample of 22,683 students.
View Article and Find Full Text PDFThe Zn receptor GPR39 is proposed to be involved in the pathophysiology of depression. GPR39 knockout (KO) animals show depressive- and anxiety-like behaviour, and resistance to conventional monoamine-based antidepressants. However, it is unclear as to which brain regions are involved in the pro-depressive phenotype of GPR39KO mice and the resistance to monoamine-targeting antidepressant treatment.
View Article and Find Full Text PDFNucleoside analogues have long served as key chemotherapeutic drugs for the treatment of viral infections and cancers. Problems associated with the development of drug resistance have led to a search for the design of nucleosides capable of bypassing point mutations in the target enzyme's binding site. As a possible answer to this, the Seley-Radtke group developed a flexible nucleoside scaffold (fleximers), where the heterocyclic purine base is split into its two components, i.
View Article and Find Full Text PDFThe National Children's Study Cognitive Health Domain Team developed detailed plans for assessing cognition longitudinally from infancy to early adulthood. These plans identify high-priority aspects of cognition that can be measured efficiently and effectively, and we believe they can serve as a model for future large-scale longitudinal research. For infancy and toddlerhood, we proposed several paradigms that collectively allowed us to assess six broad cognitive constructs: (1) executive function skills, (2) episodic memory, (3) language, (4) processing speed, (5) spatial and numerical processing, and (6) social cognition.
View Article and Find Full Text PDFHigh trait anxiety is a substantial risk factor for developing anxiety disorders and depression. While neuroinflammation has been identified to contribute to stress-induced anxiety, little is known about potential dysregulation in the neuroinflammatory system of genetically determined pathological anxiety or high trait anxiety individuals. We report microglial alterations in various brain regions in a mouse model of high trait anxiety (HAB).
View Article and Find Full Text PDFPrecise temporal and spatial regulation of gene expression in the brain is a prerequisite for cognitive processes such as learning and memory. Epigenetic mechanisms that modulate the chromatin structure have emerged as important regulators in this context. While posttranslational modification of histones or the modification of DNA bases have been examined in detail in many studies, the role of ATP-dependent chromatin remodeling factors (ChRFs) in learning- and memory-associated gene regulation has largely remained obscure.
View Article and Find Full Text PDFInt J Neuropsychopharmacol
April 2019
Background: Pathological anxiety originates from a complex interplay of genetic predisposition and environmental factors, acting via epigenetic mechanisms. Epigenetic processes that can counteract detrimental genetic risk towards innate high anxiety are not well characterized.
Methods: We used female mouse lines of selectively bred high (HAB)- vs low (LAB)-innate anxiety-related behavior and performed select environmental and pharmacological manipulations to alter anxiety levels as well as brain-specific manipulations and immunohistochemistry to investigate neuronal mechanisms associated with alterations in anxiety-related behavior.
Statistical learning can be used to gain sensitivity to many important regularities in our environment, including structure that is foundational to language and visual perception. As yet, little is known about how statistical learning takes place in the human brain, especially in children's developing brains and with regard to the broader neurobiology of learning and memory. We therefore explored the relationship between statistical learning and the thickness and volume of structures that are traditionally implicated in declarative and procedural memory, focusing specifically on the left inferior PFC, the hippocampus, and the caudate during early childhood (ages 5-8.
View Article and Find Full Text PDFCa-influx through L-type Ca-channels (LTCCs) is associated with activity-related stressful oscillations of Ca levels within dopaminergic (DA) neurons in the substantia nigra (SN), which may contribute to their selective degeneration in Parkinson's disease (PD). LTCC blockers were neuroprotective in mouse neurotoxin models of PD, and isradipine is currently undergoing testing in a phase III clinical trial in early PD. We report no evidence for neuroprotection by pretreatment with therapeutically relevant isradipine plasma levels, or Ca1.
View Article and Find Full Text PDFUsing the enzymatic transglycosylation reaction β-d-ribo- and 2'-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient.
View Article and Find Full Text PDFThe aim of the present study was to assess whether dietary magnesium deficiency can alter distribution of macroelements and trace elements in different organs and tissues. Experiments were carried out on 12 adult female Wistar rats, which were fed either a diet with low Mg content (≤20mgkg of diet) (LMgD) or a diet with daily recommended Mg content (≈500mgkg) as control group (CG) for 70 days. On the 70th day of the experiment heart, aorta, femoral skeletal muscle, forebrain, cerebellum, pituitary gland, thyroid gland, ovaries, uterus, liver, kidneys, and spleen were taken for analysis of mineral content.
View Article and Find Full Text PDFGlutamate-mediated excitotoxicity involving N-methyl-d-aspartate (NMDA) receptors has been recognized as a final common outcome in pathological conditions involving death of retinal ganglion cells (RGCs). Overstimulation of NMDA receptors results in influx of calcium (Ca) and sodium (Na) ions and efflux of potassium (K). NMDA receptors are blocked by magnesium (Mg).
View Article and Find Full Text PDFMagnesium deficiency (MgD) has been shown to impact numerous biological processes at the cellular and molecular levels. In the present review, we discuss the relationship between MgD and oxidative stress (OS). MgD is accompanied by increased levels of OS markers such as lipid, protein and DNA oxidative modification products.
View Article and Find Full Text PDFExpression of learned stimulus-reward associations based on context is essential for regulation of behavior to meet situational demands. Contextual regulation improves during development, although the developmental progression of relevant neural and cognitive processes is not fully specified. We therefore measured neural correlates of flexible, contextual expression of stimulus-reward associations in pre/early-adolescent children (ages 9-13 years) and young adults (ages 19-22 years).
View Article and Find Full Text PDFL-type voltage gated Ca(2+) channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms Cav1.2 and Cav1.
View Article and Find Full Text PDFA wide range of natural purine analogues was used as probe to assess the mechanism of recognition by the wild-type (WT) E. coli purine nucleoside phosphorylase (PNP) versus its Ser90Ala mutant. The results were analyzed from viewpoint of the role of the Ser90 residue and the structural features of the bases.
View Article and Find Full Text PDFWorking memory develops slowly: Even by age 8, children are able to maintain only half the number of items that adults can remember. Neural substrates that support performance on working memory tasks also have a slow developmental trajectory and typically activate to a lesser extent in children, relative to adults. Little is known about why younger participants elicit less neural activation.
View Article and Find Full Text PDFMagnesium (Mg) deficiency is implicated in the development of numerous disorders of the cardiovascular system. Moreover, the data regarding the efficacy of different magnesium compounds in the correction of impaired functions due to low magnesium intake are often fragmentary and inconsistent. The aim of this study was to compare the effects of the most bioavailable Mg compounds (Mg l-aspartate, Mg N-acetyltaurate, Mg chloride, Mg sulphate and Mg oxybutyrate) on systemic inflammation and endothelial dysfunction in rats fed a low Mg diet for 74 days.
View Article and Find Full Text PDFCognitive conflict detection and resolution develops with age across childhood and likely supports age-related increases in other aspects of cognitive and emotional development. Little is known about the neural correlates of conflict detection and resolution in early childhood. In the current study, we investigated age-related change in neural recruitment during a blocked spatial-incompatibility task (Simon task) in children ages 5-10 years using fMRI.
View Article and Find Full Text PDFAcross development children show marked improvement in their executive functions (EFs), including the ability to hold information in working memory and to deploy cognitive control, allowing them to ignore prepotent responses in favor of newly learned behaviors. How does the brain support these age-related improvements? Age-related cortical gray-matter thinning, thought to result from selective pruning of inefficient synaptic connections and increases in myelination, may support age-related improvements in EFs. Here we used structural MRI to measure cortical thickness.
View Article and Find Full Text PDFYoung children often perseverate, engaging in previously correct, but no longer appropriate behaviors. One account posits that such perseveration results from the use of stimulus-specific representations of a situation, which are distinct from abstract, generalizable representations that support flexible behavior. Previous findings supported this account, demonstrating that only children who flexibly switch between rules could generalize their behavior to novel stimuli.
View Article and Find Full Text PDFBackground: The beneficial effects of magnesium (Mg) salts on central manifestations of Mg deficiency are well known. Mg replacement therapy can be effective to prevent some of the serious depression-like and anxiety-related behaviour sequelae of Mg deficiency. However, few experimental studies have been undertaken on Mg-deficiency-induced behavioural changes.
View Article and Find Full Text PDFWhy do people perseverate, repeating prior behaviours that are no longer appropriate? Many accounts point to isolated deficits in processes such as inhibition or attention. We instead posit a fundamental difference in rule representations: flexible switchers use active representations that rely on later-developing prefrontal cortical areas and are more abstract, whereas perseverators use latent representations that rely on earlier-developing posterior cortical and subcortical areas and are more stimulus-specific. Thus, although switchers and perseverators should apply the rules they use to familiar stimuli equally reliably, perseverators should show unique limitations in generalizing their rules to novel stimuli, a process that requires abstract representations.
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