[Show abstract][Hide abstract] ABSTRACT: The novel protein p33MONOX (p33Monooxygenase) was over-expressed in neuroblastoma cells demonstrating its inhibitory effect on the phosphorylation of the App (amyloid precursor protein) and Bcl2 (B-cell lymphoma 2) proteins but mediating higher activation of Mapk1/3 (mitogen-activated protein kinase 1/3). We employed a variety of cell biology techniques to show the localization of p33MONOX to the cytoplasm of pyramidal neurons in the mouse brain hippocampus. We also carried out a yeast-two-hybrid screening plus co-immunoprecipitation and bio-informatics to determine COBRA1 (cofactor of BRCA1 (breast cancer type 1)), NOL12 (nucleolar protein 12), and PRNP (prion protein) as p33MONOX-interacting proteins. Bio-computational analyses revealed a flavine-containing monooxygenase (FMO)-1 motif, thus linking p33MONOX to a group of previously characterized proteins, the MICALs (molecule interacting with CasL). Concluding, p33MONOX might regulate pre- and post-transcriptional control of dynamic processes related to growth cone guidance.
[Show abstract][Hide abstract] ABSTRACT: The effect of neurotrophin-4 (Ntf4) on mouse embryonic (day-14) neural stem cell (mE14-NSC) fate determination and the mechanisms involved were investigated. Using primary mE14-NSCs, immunocytochemistry and molecular-cell biological methods, such as Western-blotting, we characterized the effect of Ntf4 on mE14-NSC differentiation. Obtained in-vitro data revealed an interesting phenomenon of Ntf4 action resulting in enhanced mE14-NSC commitment to progenitor cells of the neuronal lineage. During this process, Ntf4 suppresses the interleukin 6 (Il6) family receptor and the Notch signalling pathways by modulating their specific receptor cleavages. The observed lineage commitment is controlled via an Ntf4-mediated modulation of protein kinase B (PKB/Akt) activity and characterized by a decreased Stat3 (signal transducer and activator of transcription-3) phosphorylation status. These findings suggest that the Ntf4-activated signalling cascade is responsible for initiating a concert among sheddases, kinases, and phosphatases to mediate neurogenesis.
[Show abstract][Hide abstract] ABSTRACT: Classification of brain tissues assists for detecting brain tumors and for quantifying the cerebral atrophy. Almost of conventional methods assign the same class to voxels that have same MR signal independent of their locations. So, their methods are unsuitable for MR images with intensity nonuniformity (INU) artifact. This article proposes an automated method that locally classifies the brain tissues by adapting a fuzzy model that represents transit of MR signals on a line that draws from the gray matter to the white matter. Also, this article evaluates and discusses the proposed method and compares with the conventional method.
[Show abstract][Hide abstract] ABSTRACT: The protein family of the neurotrophins (NTs) comprises structurally and functionally related molecules such as nerve growth factor (NGF) which influences the proliferation, differentiation, survival and death of neuronal cells. In addition to their established functions for cell survival, NTs also mediate higher brain activities such as learning and memory. Changes in NT expression levels have thus been implicated in neurological diseases such as Alzheimer's disease (AD), an age-related neurodegenerative disorder that is characterized by progressive loss of memory and deterioration of higher cognitive functions. The present review provides an overview of the functional role of NGF in neural stem cells and AD while pointing to a potential application of this peptide for the treatment of AD.
[Show abstract][Hide abstract] ABSTRACT: Cerebral metabolism in chronic renal failure (CRF) patients has not been fully evaluated. This study examined cerebral metabolites in CRF, using proton magnetic resonance spectroscopy (MRS).
Subjects comprised 19 CRF patients and 21 healthy volunteers. Spectra were acquired from voxels of interest positioned in the parietal gray and white matter, and concentrations of the following cerebral metabolites were measured: N-acetyl group (NA), creatine + phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol and glutamate + glutamine. Among the 19 CRF patients, 9 who were started on hemodialysis (HD) underwent careful follow-up. Proton MRS was performed before and about 2 weeks after starting HD. In six patients in whom follow-up was possible, a third MRS was performed after about 18 months.
The NA/Cr ratio was not significantly changed in CRF. However, elevations in the Cho/Cr ratio were found in both gray and white matter compared with controls. To the best of our knowledge, this is the first report of positive correlations between the Cho/Cr ratio in both regions and serum osmotic pressure. Compared with baseline data, no significant changes in cerebral metabolite ratios were found about 2 weeks after starting HD. About 18 months after starting HD, however, the elevated Cho/Cr ratio was significantly reduced in the gray matter and tended to be reduced in the white matter.
Cho appear to play an important role in the regulation of cerebral metabolism to compensate for alterations in serum osmotic pressure in CRF, and HD may correct this abnormal cerebral metabolism.
[Show abstract][Hide abstract] ABSTRACT: Measurement of volume and surface area of the frontal, parietal, temporal and occipital lobes from magnetic resonance (MR) images shows promise as a method for use in diagnosis of dementia. This article presents a novel computer-aided system for automatically segmenting the cerebral lobes from 3T human brain MR images. Until now, the anatomical definition of cerebral lobes on the cerebral cortex is somewhat vague for use in automatic delineation of boundary lines, and there is no definition of cerebral lobes in the interior of the cerebrum. Therefore, we have developed a new method for defining cerebral lobes on the cerebral cortex and in the interior of the cerebrum. The proposed method determines the boundaries between the lobes by deforming initial surfaces. The initial surfaces are automatically determined based on user-given landmarks. They are smoothed and deformed so that the deforming boundaries run along the hourglass portion of the three-dimensional shape of the cerebrum with fuzzy rule-based active contour and surface models. The cerebrum is divided into the cerebral lobes according to the boundaries determined using this method. The reproducibility of our system with a given subject was assessed by examining the variability of volume and surface area in three healthy subjects, with measurements performed by three beginners and one expert user. The experimental results show that our system segments the cerebral lobes with high reproducibility.
[Show abstract][Hide abstract] ABSTRACT: In the mammalian brain, four neurotrophins have been identified: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5). NGF exerts an important role in the development and functions of the central and peripheral nervous system. However, it has recently been documented that several types of immune cells, such as mast cells, lymphocytes, basophils and eosinophils, produce, store and release NGF. Accumulating preclinical and clinical data indicate that dysfunctions of NGF and the other neurotrophins may contribute to impaired immune responses and concentration of NGF frequently correlates with disease severity. Thus, the aim of this study was to elucidate the potential signaling mechanisms of cytokine- neurotrophins interactions contributing to increased NGF levels. Our data show that the transcription factor NF-kappaB plays a pivotal role in regulating B-cell-derived NGF expression.
[Show abstract][Hide abstract] ABSTRACT: By recalling gustatory memories, it is possible to generate vivid gustatory perceptions in the absence of gustatory inputs. This gustatory image influences our gustatory processing. However, the mechanism of the "top-down" modulation of gustatory perception in the human is still unclear. Our findings propose a new perspective on the neural basis of gustatory processing. Although gustatory imagery and gustatory perception shared common parts of neural substrates, there was an asymmetrical topography of activation in the insula: the left insula was predominantly activated by gustatory imagery tasks. In addition, the middle and superior frontal gyri were not activated by gustatory perception but they participated in the generation of gustatory hallucinations. These regions in the frontal cortex may mediate the "top-down" control of retrieving gustatory information from the storage of long-term memories.
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is one of the most common and challenging neurodegenerative diseases in humans and is characterized by: progressive impairment in cognitive function, degeneration of cholinergic neurons of the basal forebrain (CBF), neurofibrillary tangles and amyloid beta-peptide (Abeta) depositions. The amyloid precursor protein (APP) is a transmembrane protein of which abnormal processing produces Abeta that is associated with the pathogenesis of AD. Neurotrophic factors have attracted much attention for their potential as a remedy for neurological disorders. In this regard, nerve growth factor (NGF) has generated a great interest as a potential target for the treatment of AD. This interest is based on the observation that CBF neurons, which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus, undergo selective and severe degeneration in advanced AD and that the survival of CBF neurons depends upon NGF and its receptors, namely, trkA and p75NTR. This review focuses on recent findings about APP, NGF and their potential signaling-connections to the protein encoded by the 'Sunday-driver' (SYD) gene.
Restorative neurology and neuroscience 02/2004; 22(2):131-6. · 2.49 Impact Factor