The neurotrophins are a family of secreted proteins that potently regulate diverse neuronal responses. Family members include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin 4/5(NT4/5). Neurotrophins bind the Trks receptor family (TrkA, B, C). NGF is the preferred ligand for TrkA, BDNF and NT4/5 are preferred for TrkB, and NT3 for TrkC, although NT3 also binds with less affinity to TrkA and TrkB. During my PhD I have focused my interest in understanding how neurotrophins regulate gene expression and, in particular, how BDNF does this through its high affinity receptor TrkB during neurogenesis. In order to answer this question, I planned to adopt the following approaches. First, to analyze global changes in gene expression after TrkB/BDNF activation, using microarray technology. Second, once a set of regulated genes was identified, to characterize the regulation of these genes at the promoter level, in order to understand which common elements are important for their regulation. The high-density oligonucleotide array of Affymetrix was performed using mRNAs that were obtained from cortical neurons of wild type mouse embryos (E15.5), and of mouse embryos possessing TrkB receptors mutated at either tyrosine 515 (trkB/shc point signaling mutants), or tyrosine 816 (trkB/plc-g point signaling mutants), or at both sites. In all cases the primary neurons were either unstimulated or stimulated with BDNF. The sensitivity of the Affymetrix system allowed me to identify a set of transcription factors that showed a higher fold induction compared to the others class of genes. This group consisted of: egr1, egr2, c-fos and mGIF/Tieg1. These genes were found to be differentially regulated in the signaling point mutant mice. Although the promoter of mGif/TIEG1 is not yet characterized and also the function of this gene is not completely clear, egr1, egr2 and c-fos are well characterized, and, several data suggest that these.

Gene expression is an active ongoing process that maintains a functional CNS, as proteins are being made on a continual basis. Processes such as learning and memory, nerve cell repair and regeneration and its response to stress are critically dependent on gene expression. This volume highlights the role of gene expression in normal CNS function, and presents many research methods at the cutting edge of neuroscience, which will provide insight into therapeutic approaches through which the control of gene expression may be used in the treatment of many nervous system diseases.

Alzheimer's disease is the most common form of dementia in the elderly; 450,000 people in the UK and 4.5 million people in the USA suffer with this disease. This 3rd edition of Neurobiology of Alzheimer's Disease gives a comprehensive and readable introduction to the disease, from molecular pathology to clinical practice. The book is intended for readers new to the field, and it also covers an extensive range of themes for those with in-depth knowledge of Alzheimer's disease. It will therefore act either as an introduction to the whole field of neurodegeneration or it will help experienced researchers to access the latest research in specialist topics. Each chapter is written by eminent scientists leading their fields in neuropathology, clinical practice and molecular neurobiology; appendices detail disease-associate proteins, their sequences, familial mutations and known structures. It will be essential reading for students interested in neurodegeneration and for researchers and clinicians, giving a coherent and cohesive approach to the whole area of research, and allowing access at different levels. For those in the pharmaceutical industry it describes the underlying molecular mechanisms involved in the pathogenesis of Alzheimer's disease and explains how current and potential therapeutics may work.

Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.

Traumatic spinal cord injury (SCI) results in changes to the anatomical, neurochemical, and physiological properties of cells in the central and peripheral nervous system. Neurotrophins, acting by binding to their cognate Trk receptors on target cell membranes, contribute to modulation of anatomical, neurochemical, and physiological properties of neurons in sensorimotor circuits in both the intact and injured spinal cord. Neurotrophin signaling is associated with many post-SCI changes including maladaptive plasticity leading to pain and autonomic dysreflexia, but also therapeutic approaches such as training-induced locomotor improvement. Here we characterize expression of mRNA for neurotrophins and Trk receptors in lumbar dorsal root ganglia (DRG) and spinal cord after two different severities of mid-thoracic injury and at 6 and 12 weeks post-SCI. There was complex regulation that differed with tissue, injury severity, and survival time, including reversals of regulation between 6 and 12 weeks, and the data suggest that natural regulation of neurotrophins in the spinal cord may continue for months after birth. Our assessments determined that a coordination of gene expression emerged at the 12 week post-SCI time point and bioinformatic analyses address possible mechanisms. Additionally, we sought to determine if the regulatory patterns we observed were perhaps due to an inflammatory molecule that mediated the coordinated expression pattern that we observed at 12 weeks post injury, and identified the chemokine CCL2 as a potential candidate gene.