Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Description and Predictive Factors of individual outcomes in a refugee camp based mental health intervention (Beirut, Lebanon)

There is little evidence on the effectiveness of services for the care of people with mental disorders among refugee populations. Médecins sans Frontières (MSF) has established a mental health centre in a mixed urban-refugee population in Beirut to respond to the significant burden of mental health problems. Patients received comprehensive care through a multidisciplinary team. A cohort of people with common and severe mental disorders has been analysed between December 2008 and June 2011 to evaluate individual outcomes of treatment in terms of functionality

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Number and Size Distribution of Colorectal Adenomas under the Multistage Clonal Expansion Model of Cancer

Colorectal cancer (CRC) is believed to arise from mutant stem cells in colonic crypts that undergo a well-characterized progression involving benign adenoma, the precursor to invasive carcinoma. Although a number of (epi)genetic events have been identified as drivers of this process, little is known about the dynamics involved in the stage-wise progression from the first appearance of an adenoma to its ultimate conversion to malignant cancer. By the time adenomas become endoscopically detectable (i.e., are in the range of 1–2 mm in diameter), adenomas are already comprised of hundreds of thousands of cells and may have been in existence for several years if not decades. Thus, a large fraction of adenomas may actually remain undetected during endoscopic screening and, at least in principle, could give rise to cancer before they are detected. It is therefore of importance to establish what fraction of adenomas is detectable, both as a function of when the colon is screened for neoplasia and as a function of the achievable detection limit. To this end, we have derived mathematical expressions for the detectable adenoma number and size distributions based on a recently developed stochastic model of CRC. Our results and illustrations using these expressions suggest (1) that screening efficacy is critically dependent on the detection threshold and implicit knowledge of the relevant stem cell fraction in adenomas, (2) that a large fraction of non-extinct adenomas remains likely undetected assuming plausible detection thresholds and cell division rates, and (3), under a realistic description of adenoma initiation, growth and progression to CRC, the empirical prevalence of adenomas is likely inflated with lesions that are not on the pathway to cancer

Explicit Logic Circuits Predict Local Properties of the Neocortex's Physiology and Anatomy

Background: Two previous articles proposed an explicit model of how the brain processes information by its organization of synaptic connections. The family of logic circuits was shown to generate neural correlates of complex psychophysical phenomena in different sensory systems. Methodology/Principal Findings: Here it is shown that the most cost-effective architectures for these networks produce correlates of electrophysiological brain phenomena and predict major aspects of the anatomical structure and physiological organization of the neocortex. The logic circuits are markedly efficient in several respects and provide the foundation for all of the brain’s combinational processing of information. Conclusions/Significance: At the local level, these networks account for much of the physical structure of the neocortex as well its organization of synaptic connections. Electronic implementations of the logic circuits may be more efficient than current electronic logic arrays in generating both Boolean and fuzzy logic

From Development to Degeneration and Regeneration of the Nervous System

This book describes current information about the three areas mentioned in the title: neuronal migration and development, degenerative brain diseases, and neural plasticity and regeneration. The chapters in the first section of the book examine the cellular and molecular mechanisms by which neurons are generated from the ventricular zone in the forebrain and migrate to their destinations in the cerebral cortex. This description of cortical development also includes discussions of the Cajal-Retzius cell. Another chapter provides insight about the development of another forebrain region, the hypothalamus. The remaining chapters of the first section examine the clinical relevance of brain development in certain disease states in humans. The second section begins with details about the dopaminergic neurons in the substantia niger and their loss in Parkinson's disease. Two subsequent chapters describe changes in brain aging, including changes in the numbers of myelinated axons. Other chapters in this section describe important cellular and molecular changes found in Alzheimer's disease and human epilepsy. The last section begins with a chapter on how the brain's own stem cells provide newly generated neurons to the hippocampal dentate gyrus and how these neurons become integrated into neural circuitry. Then two chapters examine some of the neuroplastic changes that take place in motor and sensory cortices of awake behaving primates. The concluding two chapters address the issue of regeneration in the injured spinal cord and the factors that may contribute to its success