Induction of a novel form of hippocampal long-term depression by muscimol: involvement of GABAA but not glutamate receptors.

1. Unlike long-term potentiation, long-term depression (LTD) in the central nervous system remains poorly understood. The present study was undertaken to investigate the role of GABAA receptors in LTD and synaptic plasticity. 2. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). 3. Muscimol induced a time- and concentration-dependent LTD of the amplitude of orthodromic potentials. Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 s reversed the LTD induced by muscimol. Muscimol also induced LTD in the absence of electrical stimulation. 4. Adenosine decreased the spike size in a concentration-dependent manner, but failed to induce LTD. 5. Alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 microM), potentiated the inhibitory effect of muscimol on the population spike size, including concentrations which were not effective by themselves. Both steroids were able to potentiate the ability of muscimol to induce LTD. 6. Bicuculline, 5 microM, reversed the LTD induced by muscimol, 10 microM. 7. The NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (2-AP5), the NMDA/metabotropic antagonist 2-AP3 and selective metabotropic antagonist L-(+)-2-amino-3-phosphonopropionic acid (L(+)-AP3) failed to modify the LTD. Similarly, quisqualic acid and (1S, 3R)-aminocyclopentane dicarboxylic acid (ACPD) a selective agonist at metabotropic receptors did not induce LTD or short-term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outbreak of serogroup C meningococcal disease caused by a variant of Neisseria meningitidis serotype 2a ET-15 in a community of men who have sex with men

We describe an outbreak, in a community of men who have sex with men, of serogroup C meningococcal disease caused by a genetic variant of the serotype 2a ET-15 Neisseria meningitidis characterized by a point mutation in the gene coding for the serotype 2a antigen. A microbiological characterization of the outbreak strain is presented in this report.     

Identification and Validation of Nutrient State-Dependent Serum Protein Mediators of Human CD4+ T Cell Responsiveness

Intermittent fasting and fasting mimetic diets ameliorate inflammation. Similarly, serum extracted from fasted healthy and asthmatic subjects’ blunt inflammation in vitro, implicating serum components in this immunomodulation. To identify the proteins orchestrating these effects, SOMAScan technology was employed to evaluate serum protein levels in healthy subjects following an overnight, 24-h fast and 3 h after refeeding. Partial least square discriminant analysis identified several serum proteins as potential candidates to confer feeding status immunomodulation. The characterization of recombinant IGFBP1 (elevated following 24 h of fasting) and PYY (elevated following refeeding) in primary human CD4⁺ T cells found that they blunted and induced immune activation, respectively. Furthermore, integrated univariate serum protein analysis compared to RNA-seq analysis from peripheral blood mononuclear cells identified the induction of IL1RL1 and MFGE8 levels in refeeding compared to the 24-h fasting in the same study. Subsequent quantitation of these candidate proteins in lean versus obese individuals identified an inverse regulation of serum levels in the fasted subjects compared to the obese subjects. In parallel, IL1RL1 and MFGE8 supplementation promoted increased CD4⁺ T responsiveness to T cell receptor activation. Together, these data show that caloric load-linked conditions evoke serological protein changes, which in turn confer biological effects on circulating CD4⁺ T cell immune responsiveness.     

Molekulare Mechanismen der Embryoimplantation im Endometrium

Human Reproduction is a very complex and surprisingly inefficient process. The embryo development and the generation of a receptive endometrium needs an exact timing and synchronization. Understanding the factors involved in preimplantation embryo development and embryo-maternal interaction and implantation is crucial for improving success rates in reproductive medicine. The purpose of the present review is to describe briefly the function of adhesion- and hormonal factors, cytokines, growth factors and metalloproteinases. A better understanding of the molecular mechanisms of implantation will be responsible for the improvement of clinical and therapeutical management of sterility, infertility and contraception.     

Multimodal imaging in photic retinopathy

Letter to the Editor