Memory and Plasticity

Entorhinal cortical thinning affects perceptual and cognitive functions in adolescents born preterm with very low birth weight (VLBW).

Early Hum Dev. 2012 Feb;88(2):103-9

Authors: Skranes J, Løhaugen GC, Evensen KA, Indredavik MS, Haraldseth O, Dale AM, Brubakk AM, Martinussen M

Abstract
BACKGROUND: The entorhinal cortex serves as an important gateway between the cerebral cortex and the hippocampus by receiving afferent information from limbic, modality sensory-specific, and multimodal association fibers from all the brain lobes.
AIM: To investigate whether thinning of entorhinal cortex is associated with reduced perceptual, cognitive and executive skills in very low birth weight (VLBW) adolescents.
STUDY DESIGN: Prospective, geographically based follow-up study of three year cohorts of preterm born VLBW children.
SUBJECTS: Forty-nine VLBW (birth weight ? 1500 g) and 58 term-born control adolescents were examined at the age of 14-15 years.
OUTCOME MEASURES: Perceptual and cognitive functions were assessed with Visual motor integration test, Grooved Pegboard test, Wechsler Intelligence Scale for Children-III and different executive function tests (Wisconsin card sorting test, Trail Making test, Knox cube test). An automated MRI technique at 1.5 T for morphometric analyses of cortical thickness was performed. Areas with cortical thinning in left and right entorhinal cortex in the VLBW group were chosen as regions of interest to look for associations between cortical thickness and clinical findings.
RESULTS: Thinning of the entorhinal cortex was correlated with low performance on perceptual and cognitive scores in the VLBW adolescents, but not in controls. In addition, thinning of the entorhinal cortices correlated with reduced performance on several executive tests, including perceptual speed and aspects of working memory.
CONCLUSIONS: Entorhinal cortical thinning is related with low IQ and reduced perceptual and executive functions in VLBW adolescents.

PMID: 21839590 [PubMed - indexed for MEDLINE]

The selective S1P receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate: translation from preclinical to clinical studies.

Br J Pharmacol. 2012 May 30;

Authors: Gergely P, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, Groenewegen A, Vitaliti A, Sing T, Luttringer O, Yang J, Gardin A, Wang N, Crumb WJ, Saltzman M, Rosenberg M, Wallström E

Abstract
BACKGROUND AND PURPOSE:? BAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P(1) and S1P(5) . S1P(1) is central for lymphocyte egress from lymph nodes and a drug target in immune-mediated diseases. The aim of the study was to characterize the immunomodulatory potential of BAF312 and the S1P receptor-mediated effects on heart rate using preclinical and human clinical data. EXPERIMENTAL APPROACH:? BAF312 was tested in a rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings of G protein-coupled inwardly rectifying potassium (GIRK) channels were carried out in human atrial myocytes. A Phase I multiple-dose trial studied the pharmacokinetics, pharmacodynamics and safety of BAF312 in 48 healthy subjects. KEY RESULTS:? BAF312 effectively suppressed EAE in rats by internalizing S1P(1) , rendering them insensitive for the egress signal from lymph nodes. In healthy volunteers, BAF312 caused preferential decreases in CD4(+) T cells, T(naïve) , T(central?memory) and B cells within 4-6 h. Cell counts returned to normal ranges within a week after therapy cessation, in line with the elimination half-life of BAF312. Despite sparing S1P(3) (associated with bradycardia in mice) BAF312 induced rapid, transient (Day 1 only) bradycardia in humans. BAF312-mediated activation of GIRK channels in human atrial myocytes can fully explain the bradycardia. CONCLUSIONS AND IMPLICATIONS:? This study illustrates species-specific differences in S1P receptor specificity for first-dose cardiac effects. Based on its profound effect on lymphocyte trafficking inhibition but with a rapid reversal of lymphocyte reduction, BAF312 may have potential as a treatment for immune-mediated diseases. © 2012 Novartis Institutes for Biomedical Research. British Journal of Pharmacology © 2012 The British Pharmacological Society.

PMID: 22646698 [PubMed - as supplied by publisher]

Regulation of T(H)2 development by CXCR5(+) dendritic cells and lymphotoxin-expressing B cells.

Nat Immunol. 2012 May 27;

Authors: León B, Ballesteros-Tato A, Browning JL, Dunn R, Randall TD, Lund FE

Abstract
Although cognate encounters between antigen-bearing dendritic cells (DCs) that express the chemokine receptor CCR7 and CCR7(+) naive T cells take place in the T cell zone of lymph nodes, it is unknown whether the colocalization of DCs and T cells in the T cell area is required for the generation of effector cells. Here we found that after infection with an intestinal nematode, antigen-bearing DCs and CD4(+) T cells upregulated the chemokine receptor CXCR5 and localized together outside the T cell zone by a mechanism dependent on the chemokine CXCL13, B cells and lymphotoxin. Notably, lymphotoxin-expressing B cells, CXCR5-expressing DCs and T cells, and CXCL13 were also necessary for development of interleukin 4 (IL-4)-producing type 2 helper T cells (T(H)2 cells), which suggests that T(H)2 differentiation can initiate outside the T cell zone.

PMID: 22634865 [PubMed - as supplied by publisher]

Set-Shifting in Adults with ADHD.

J Int Neuropsychol Soc. 2012 May 22;:1-10

Authors: Halleland HB, Haavik J, Lundervold AJ

Abstract
Difficulties related to inhibition and set-shifting have been suggested as possible endophenotypes of Attention Deficit Hyperactivity Disorder (ADHD). However, such difficulties have not been consistently found in studies using standard neuropsychological tests. This has been partly explained by the complexity of these tests and the need to include contrast measures which control for more basic functions. The purpose of the present study was to examine whether difficulties related to inhibition and set-shifting in adult ADHD patients could be revealed by the Color Word Interference Test (CWIT) from the Delis Kaplan Executive Function System (D-KEFS). A clinically recruited group of adults with ADHD (n = 60) obtained significantly lower scores than population derived controls (n = 60) on both primary summary (p < .001) and contrast measures (p = .004) of set-shifting. The differences between the groups remained statistically significant after controlling for intellectual function and working memory (p = .003). However, no significant differences between the groups were observed on any measure of inhibition. The study indicates that adults with ADHD have specific difficulties with set-shifting as measured by the CWIT, difficulties that probably also reflect problems related to executive function in their daily life. (JINS, 2012, 18, 1-10).

PMID: 22613368 [PubMed - as supplied by publisher]