Individual characteristics of pathophysiology and course of depressive episodes are at present not considered in diagnostics. There are no biological markers available that can assist in categorizing subtypes of depression and detecting molecular variances related to disease-causing mechanisms between depressed patients. Identification of such differences is important to create patient subgroups, which will benefit from medications that specifically target the pathophysiology underlying their clinical condition. To detect characteristic biological markers for major depression, we analyzed the cerebrospinal fluid (CSF) proteome of depressed vs control persons, using two-dimensional polyacrylamide gel electrophoresis and time-of-flight (TOF) mass spectrometry peptide profiling. Proteins of interest were identified by matrix-assisted laser desorption ionization TOF mass spectrometry (MALDI-TOF-MS). Validation of protein markers was performed by immunoblotting. We found 11 proteins and 144 peptide features that differed significantly between CSF from depressed patients and controls. In addition, we detected differences in the phosphorylation pattern of several CSF proteins. A subset of the differentially expressed proteins implicated in brain metabolism or central nervous system disease was validated by immunoblotting. The identified proteins are involved in neuroprotection and neuronal development, sleep regulation, and amyloid plaque deposition in the aging brain. This is one of the first hypothesis-free studies that identify characteristic protein expression differences in CSF of depressed patients. Proteomic approaches represent a powerful tool for the identification of disease markers for subgroups of patients with major depression.

Brain proteome analysis of mice selectively bred for either high or low anxiety-related behavior revealed quantitative and qualitative protein expression differences. The enzyme glyoxalase-I was consistently expressed to a higher extent in low anxiety as compared with high anxiety mice in several brain areas. The same phenotype-dependent difference was also found in red blood cells with normal and cross-mated animals showing intermediate expression profiles of glyoxalase-I. Another protein that showed a different mobility during two-dimensional gel electrophoresis was identified as enolase phosphatase. The presence of both protein markers in red or white blood cells, respectively, creates the opportunity to screen for their expression in clinical blood specimens from patients suffering from anxiety. Biomarkers are measures of biological parameters of disease that also can predict which new molecular entities will be effective and safe in treating patients (1). We have focused our biomarker discovery efforts on the analysis of mouse models (2) to avoid the interindividual differences of human specimens that often result in a low biomarker signal to background noise ratio.The manifestation of anxiety in a number of psychiatric disorders such as generalized anxiety disorder, depression, panic attacks, phobias, obsessive-compulsive disorders, and post-traumatic stress disorder (3) highlights the importance of gaining a better understanding of associated reliable biomarkers in proper animal models. An animal model to study behavioral, neuroendocrine, and genetic concomitants of trait anxiety including psychopathology should represent a good approximation to score symptoms of anxiety disorders and possibly comorbid depression (4 -6). To avoid interstrain comparisons, which are likely to reveal differences in more than just anxiety-related indices, we have been using intrastrain breeding approaches to focus on particular traits, including anxiety-related behavior (7), depression-like behavior (8), and avoidance behavior or receptor functions likely to be associated with differences in anxiety (9 -12). The technique of selective bidirectional breeding enhances the representation of genetic material associated with a particular trait shifting the animals' phenotype bidirectionally from the strain mean (13).Genetic approaches currently available in the mouse make this model organism particularly powerful for the functional analysis of candidate genes and in defining gene products underlying trait anxiety and possibly depression (14). For this reason we have generated and validated hyperanxious (HAB-M 1 ) and hypoanxious (LAB-M) CD1 mouse lines as model of extremes in trait anxiety and have used comparative proteomics to identify anxiety-related protein markers (2). One of the identified markers that we have reported previously, glyoxalase-I (2), showed expression level differences between HAB-M and LAB-M animals and recently has attracted increasing attention for its role in psychopathogenic mechanisms (15). The other pro...

Primary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.

Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE-specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase-related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration.