Molecular Sex Differences in Human Serum

Background: Sex is an important factor in the prevalence, incidence, progression, and response to treatment of many medical conditions, including autoimmune and cardiovascular diseases and psychiatric conditions. Identification of molecular differences between typical males and females can provide a valuable basis for exploring conditions differentially affected by sex. Methodology/Principal Findings: Using multiplexed immunoassays, we analyzed 174 serum molecules in 9 independent cohorts of typical individuals, comprising 196 males and 196 females. Sex differences in analyte levels were quantified using a meta-analysis approach and put into biological context using k-means to generate clusters of analytes with distinct biological functions. Natural sex differences were established in these analyte groups and these were applied to illustrate sexually dimorphic analyte expression in a cohort of 22 males and 22 females with Asperger syndrome. Reproducible sex differences were found in the levels of 77 analytes in serum of typical controls, and these comprised clusters of molecules enriched with distinct biological functions. Analytes involved in fatty acid oxidation/hormone regulation, immune cell growth and activation, and cell death were found at higher levels in females, and analytes involved in immune cell chemotaxis and other indistinct functions were higher in males. Comparison of these naturally occurring sex differences against a cohort of people with Asperger syndrome indicated that a cluster of analytes that had functions related to fatty acid oxidation/hormone regulation was associated with sex and the occurren

Evidence for a wide extra-astrocytic distribution of S100B in human brain

BACKGROUND: S100B is considered an astrocytic in-situ marker and protein levels in cerebrospinal fluid (CSF) or serum are often used as biomarker for astrocytic damage or dysfunction. However, studies on S100B in the human brain are rare. Thus, the distribution of S100B was studied by immunohistochemistry in adult human brains to evaluate its cell-type specificity. RESULTS: Contrary to glial fibrillary acidic protein (GFAP), which selectively labels astrocytes and shows only faint ependymal immunopositivity, a less uniform staining pattern was seen in the case of S100B. Cells with astrocytic morphology were primarily stained by S100B in the human cortex, while only 20% (14–30%) or 14% (7–35%) of all immunopositive cells showed oligodendrocytic morphology in the dorsolateral prefrontal and temporal cortices, respectively. In the white matter, however, most immunostained cells resembled oligodendrocytes [frontal: 75% (57–85%); temporal: 73% (59–87%); parietal: 79% (62–89%); corpus callosum: 93% (86–97%)]. S100B was also found in ependymal cells, the choroid plexus epithelium, vascular endothelial cells, lymphocytes, and several neurones. Anti-myelin basic protein (MBP) immunolabelling showed an association of S100B with myelinated fibres, whereas GFAP double staining revealed a distinct subpopulation of cells with astrocytic morphology, which solely expressed S100B but not GFAP. Some of these cells showed co-localization of S100B and A2B5 and may be characterized as O2A glial progenitor cells. However, S100B was not detected in microglial cells, as revealed by double-immunolabelling with HLA-DR. CONCLUSION: S100B is localized in many neural cell-types and is less astrocyte-specific than GFAP. These are important results in order to avoid misinterpretation in the identification of normal and pathological cell types in situ and in clinical studies since S100B is continuously used as an astrocytic marker in animal models and various human diseases

Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control

Identification of subgroups of Schizophrenia patients with changes in either immune or growth factor and hormonal pathways

Schizophrenia is a heterogeneous disorder normally diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. However, these criteria do not necessarily reflect differences in underlying molecular abnormalities of the disorder. Here, we have used multiplexed immunoassay analyses to measure immune molecules, growth factors, and hormones important to schizophrenia in acutely ill antipsychotic-naive patients (n = 180) and matched controls (n = 398). We found that using the resulting molecular profiles, we were capable of separating schizophrenia patients into 2 significantly distinct subgroups with predominant molecular abnormalities in either immune molecules or growth factors and hormones. These molecular profiles were tested using an independent cohort, and this showed the same separation into 2 subgroups. This suggests that distinct abnormalities occur in specific molecular pathways in schizophrenia patients. This may be of relevance for intervention studies that specifically target particular molecular mechanisms and could be a first step to further define the complex schizophrenia syndrome based on molecular profiles