Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their components

The decrease in plasticity that occurs in the central nervous system during postnatal development is accompanied by the appearance of perineuronal nets (PNNs) around the cell body and dendrites of many classes of neuron. These structures are composed of extracellular matrix molecules, such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan (HA), tenascin-R, and link proteins. To elucidate the role played by neurons and glial cells in constructing PNNs, we studied the expression of PNN components in the adult rat cerebellum by immunohistochemistry and in situ hybridization. In the deep cerebellar nuclei, only large excitatory neurons were surrounded by nets, which contained the CSPGs aggrecan, neurocan, brevican, versican, and phosphacan, along with tenascin-R and HA. Whereas both net-bearing neurons and glial cells were the sources of CSPGs and tenascin-R, only the neurons expressed the mRNA for HA synthases (HASs), cartilage link protein, and link protein Bral2. In the cerebellar cortex, Golgi neurons possessed PNNs and also synthesized HASs, cartilage link protein, and Bral2 mRNAs. To see whether HA might link PNNs to the neuronal cell surface by binding to a receptor, we investigated the expression of the HA receptors CD44, RHAMM, and LYVE-1. No immunolabelling for HA receptors on the membrane of net-bearing neurons was found. We therefore propose that HASs, which can retain HA on the cell surface, may act as a link between PNNs and neurons. Thus, HAS and link proteins might be key molecules for PNN formation and stability.     

Impact of sampling rate on statistical significance for single subject fMRI connectivity analysis

A typical time series in functional magnetic resonance imaging (fMRI) exhibits autocorrelation, that is, the samples of the time series are dependent. In addition, temporal filtering, one of the crucial steps in preprocessing of functional magnetic resonance images, induces its own autocorrelation. While performing connectivity analysis in fMRI, the impact of the autocorrelation is largely ignored. Recently, autocorrelation has been addressed by variance correction approaches, which are sensitive to the sampling rate. In this article, we aim to investigate the impact of the sampling rate on the variance correction approaches. Toward this end, we first derived a generalized expression for the variance of the sample Pearson correlation coefficient (SPCC) in terms of the sampling rate and the filter cutoff frequency, in addition to the autocorrelation and cross‐covariance functions of the time series. Through simulations, we illustrated the importance of the variance correction for a fixed sampling rate. Using the real resting state fMRI data sets, we demonstrated that the data sets with higher sampling rates were more prone to false positives, in agreement with the existing empirical reports. We further demonstrated with single subject results that for the data sets with higher sampling rates, the variance correction strategy restored the integrity of true connectivity.     

Glucose metabolism transporters and epilepsy: Only GLUT1 has an established role

The availability of glucose, and its glycolytic product lactate, for cerebral energy metabolism is regulated by specific brain transporters. Inadequate energy delivery leads to neurologic impairment. Haploinsufficiency of the glucose transporter GLUT1 causes a characteristic early onset encephalopathy, and has recently emerged as an important cause of a variety of childhood or later‐onset generalized epilepsies and paroxysmal exercise‐induced dyskinesia. We explored whether mutations in the genes encoding the other major glucose (GLUT3) or lactate (MCT1/2/3/4) transporters involved in cerebral energy metabolism also cause generalized epilepsies. A cohort of 119 cases with myoclonic astatic epilepsy or early onset absence epilepsy was screened for nucleotide variants in these five candidate genes. No epilepsy‐causing mutations were identified, indicating that of the major energetic fuel transporters in the brain, only GLUT1 is clearly associated with generalized epilepsy.     

Store-operated calcium entry modulates neuronal network activity in a model of chronic epilepsy

Store-operated Ca²⁺ entry (SOCE) over the plasma membrane is activated by depletion of intracellular Ca²⁺ stores and has only recently been shown to play a role in CNS processes like synaptic plasticity. However, the direct effect of SOCE on the excitability of neuronal networks in vitro and in vivo has never been determined. We confirmed the presence of SOCE and the expression of the calcium sensors STIM1 and STIM2, which convey information about the calcium load of the stores to channel proteins at the plasma membrane, in neurons and astrocytes. Inhibition of SOCE by pharmacological agents 2-APB and ML-9 reduced the steady-state neuronal Ca²⁺ concentration, reduced network activity, and increased synchrony of primary neuronal cultures grown on multi-electrode arrays, which prompted us to elucidate the relative expression of STIM proteins in conditions of pathologic excitability. Both proteins were increased in brains of chronic epileptic rodents and strongly expressed in hippocampal specimens from medial temporal lobe epilepsy patients. Pharmacologic inhibition of SOCE in chronic epileptic hippocampal slices suppressed interictal spikes and rhythmized epileptic burst activity. Our results indicate that SOCE modulates the activity of neuronal networks in vitro and in vivo and delineates SOCE as a potential drug target.     

Intracellular transport of Toxoplasma gondii through the blood-brain barrier

Toxoplasma gondii establishes latent infection in the central nervous system of immunocompentent hosts. Toxoplasmic encephalitis is a life threatening reactivation of latent infection in the brain of immunocompromised patients. To further understand the mechanisms of entry into the brain of T. gondii we investigated host molecules and cells involved in the passage of the parasite through the blood-brain barrier. First, using microarrays brain endothelial cells were found to upregulate, among others, chemokines and adhesion molecules following infection with tachyzoites. Using flow cytometry we observed upregulated ICAM-1 expression on the surface of brain endothelial cells following infection; ICAM-1 expression was further increased after pre-incubation with IFN-γ. Compared to RH tachyzoites, ME49 tachyzoites induced a stronger upregulation of ICAM-1 and an earlier and stronger IL-6 and MCP-1 secretion by brain endothelial cells. Using an in vitro coculture model of the BBB (primary glia cells and brain endothelial cells) we found a stronger migration of infected antigen-presenting cells compared to lymphocytes (4.63% vs. 0.6% of all cells) across the BBB. Among all antigen-presenting cells CD11b(+)/CD11c(+) cells showed the highest infection rate, whereas the majority of infected cells that migrated through the blood-brain barrier were CD11b(+)/CD11c(-) cells. Infection of PBMCs with type I or type II Toxoplasma strains resulted in similar patterns of cell migration across the in vitro BBB model. In conclusion, these results suggest that T. gondii modulates gene expression of brain endothelial cells to promote its own migration through the blood-brain barrier in a 'Trojan horse' manner. Cells expressing CD11b either with or without CD11c are likely candidate cells for the intracellular transport of T. gondii across the BBB. T. gondii type I and type II strains induced similar migration patterns of antigen-presenting cells across the in vitro BBB.     

The Association Between Autistic Traits and Disordered Eating is Moderated by Sex/Gender and Independent of Anxiety and Depression

Journal of Autism and Developmental Disorders - Previous studies have reported positive correlations between autistic traits and disordered eating, though it is unclear whether the association is...     

Older adults’ preferences for exercising alone versus in groups: Considering contextual congruence

Background: A growing body of research suggests that older exercisers prefer to exercise alone rather than in group-based settings. One limitation of these studies, however, has been that researchers have failed to take into account the age-related characteristics of groups when asking adults about their preferences for exercise settings.Purpose: The overall purpose of this study was to examine the exercise preferences of 947 adults for involvement in standard exercise classes populated by participants from various categories across the age spectrum.Results: The results revealed that when faced with the prospect of exercising with considerably older or younger exercisers, participants found such an exercise context to be largely unappealing. However, in accordance with the basic tenets of self-categorization theory, the results revealed that older and younger adults alike express a positive preference for exercising in standard exercise classes comprised of similarly aged participants.Conclusions: The findings of this study challenge a growing call for exercise interventions for older adults to be primarily directed at the individual-level, and suggest that group-related intervention strategies may indeed be attractive to older exercisers.     

Suicide in deaf populations: a literature review

Background  

Studies have found that deaf individuals have higher rates of psychiatric disorder than those who are hearing, while at the same time encountering difficulties in accessing mental health services. These factors might increase the risk of suicide. However, the burden of suicidal behaviour in deaf people is currently unknown.