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Callosum
Kinds of Callosum Selected AbstractsPrenatal diagnosis in a family with X-linked hydrocephalusPRENATAL DIAGNOSIS, Issue 10 2005Maria Panayi Abstract The neural cell adhesion molecule L1 is a transmembrane glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules (CAMs). Its expression is essential during embryonic development of the nervous system and it is involved in cognitive function and memory. Mutations in the L1CAM gene are responsible for four related L1 disorders; X-linked hydrocephalus/HSAS (Hydrocephalus as a result of Stenosis of the Aqueduct of Sylvius), MASA (Mental retardation, Aphasia, Shuffling gait, and Adducted thumbs) syndrome, X-linked complicated spastic paraplegia type I (SPG1) and X-linked Agenesis of the Corpus Callosum (ACC). These four disorders represent a clinical spectrum that varies both between and within families. The main clinical features of this spectrum are Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH syndrome). Since there is no biochemically assayed disease marker, molecular analysis of the L1CAM gene is the only means of confirming a clinical diagnosis. Most L1CAM mutations reported to date are point mutations (missense, nonsense, splice site) and only a few patients with larger rearrangements have been documented. We have characterised a rare intragenic deletion of the L1CAM gene in a sample of DNA extracted from a chorionic villus biopsy (CVB) performed at 12 weeks' gestation. Copyright © 2005 John Wiley & Sons, Ltd. [source] Review of animal models for autism: implication of thyroid hormoneCONGENITAL ANOMALIES, Issue 1 2006Miyuki Sadamatsu ABSTRACT,, Autism is a behaviorally defined disorder associated with characteristic impairments in social interactions and communication, as well as restricted and repetitive behaviors and interest. Its prevalence was once thought to be 2/10 000, but recently several large autism prevalence reviews revealed that the rate of occurrence was roughly 30/10 000. While it has been considered a developmental disorder, little is certain about its etiology. Neuroanatomical studies at the histological level in the brains of autistic patients provide many arguments in the etiology of autism. Results from postmortem and imaging studies have implicated many major structures of the brain including the limbic system, cerebellum, corpus callosum, basal ganglia and brainstem. There is no single biological or clinical marker for autism. While several promising candidate genes have been presented, the critical loci are yet unknown. Environmental influences such as rubella virus, valproic acid, and thalidomide exposure during pregnancy are also considered important, as concordance in monozygotic twins is less than 100% and the phenotypic expression of the disorder varies widely. It is thus hypothesized that non-genetic mechanisms contribute to the onset of autistic syndrome. In light of these ambiguities, hope is held that an animal model of autism may help elucidate matters. In this article, we overview most of the currently available animal models for autism, and propose the rat with mild and transient neonatal hypothyroidism as a novel model for autism. [source] Phenotypic differences in the brains and limbs of mutant mice caused by differences of Gli3 gene expression levelsCONGENITAL ANOMALIES, Issue 2 2001Ichiro Naruse ABSTRACT, The genetic polydactyly/arhinencephaly mouse, Pdn/Pdn, exhibits severe polydactyly both in the fore-and hindlimbs, agenesis of the olfactory bulbs, corpus callosum, anterior commissure, and hydrocephalus. A candidate gene for the Pdn mouse has been speculated to be Gli3, because Pdn has been considered to be an allele of Xt whose responsible gene has been clarified to be Gli3. Recently, it has been cleared that retro-transposons are inserted into nitron 3, upstream of zinc finger domain, of the Gli3 gene in the Pdn mouse, resulting to the severe suppression of Gli3 gene expression in Pdn/Pdn embryos. Meanwhile, XtJ/XtJ mice exhibit more severe polydactyly than that of Pdn/Pdn. Arhinencephaly and microholoprosencephaly including agenesis of the olfactory bulbs, corpus callosum, anterior commissure, hippocampal commissure, habenular commissure, and posterior commissure, and moreover, the cerebral cortical plates and hippocampus are not formed in the XtJ/XtJ mice. The XtJ/XtJ mouse has a large deletion in Gli3 structural gene and shows null expression. From these corroborations, we speculated that the differences in the Gli3 gene expression levels resulted in the phenotypic differences between the Pdn/Pdn and XtJ/XtJ mice. [source] Anomalous development of brain structure and function in spina bifida myelomeningoceleDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 1 2010Jenifer Juranek Abstract Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II malformation. Other structural anomalies are not necessarily unique to SBM, including altered development of the corpus callosum and posterior fossa. Within SBM, tremendous heterogeneity is reflected in the degree to which brain structures are atypical in qualitative appearance and quantitative measures of morphometry. Hallmark structural features of SBM include overall reductions in posterior fossa and cerebellum size and volume. Studies of the corpus callosum have shown complex patterns of agenesis or hypoplasia along its rostral-caudal axis, with rostrum and splenium regions particularly susceptible to agenesis. Studies of cortical regions have demonstrated complex patterns of thickening, thinning, and gyrification. Diffusion tensor imaging studies have reported compromised integrity of some specific white matter pathways. Given equally complex ocular motor, motor, and cognitive phenotypes consisting of relative strengths and weaknesses that seem to align with altered structural development, studies of SBM provide new insights to our current understanding of brain structure,function associations. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:23,30. [source] Corpus callosum and posterior fossa development in monozygotic females: a morphometric MRI study of Turner syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2003Susannah L Fryer BA Previous neuroimaging research in Turner syndrome (TS) has indicated parietal lobe anomalies, while anomalies in other brain loci have been less well-substantiated. This study focused on potential cerebellar abnormalities and possible disruptions of interhemispheric (parietal) callosal connections in individuals with TS. Twenty-seven female children and adolescents with TS (mean age 13 years, SD 4 years 2 months) and 27 age-matched female control individuals (mean age 13 years 2 months, SD 4 years 1 month) underwent MRI. Age range of all participants was 7 to 20 years. Morphometric analyses of midline brain structures were conducted using standardized, reliable methods. When compared with control participants, females with TS showed reduced areas of the genu of the corpus callosum, the pons, and vermis lobules VI,VII, and an increased area of the fourth ventricle. No group difference in intracranial area measurements was observed. The reduced area of the genu in TS may reflect compromised connectivity between inferior parietal regions. Further, cerebellar vermis hypoplasia associated with TS agrees with literature that suggests the posterior fossa as a region prone to structural alterations in the face of early developmental insult. [source] Brain dysmorphology in individuals with severe prenatal alcohol exposureDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 3 2001Sarah L Archibald MA Our previous studies revealed abnormalities on structural MRI (sMRI) in small groups of children exposed to alcohol prenatally. Microcephaly, disproportionately reduced basal ganglia volume, and abnormalities of the cerebellar vermis and corpus callosum were demonstrated. The present study used sMRI to examine in detail the regional pattern of brain hypoplasia resulting from prenatal exposure to alcohol using a higher resolution imaging protocol and larger sample sizes than reported previously. Fourteen participants (mean 11.4 years; eight females, six males) with fetal alcohol syndrome (FAS) and 12 participants (mean 14.8 years; four females, eight males) with prenatal exposure to alcohol (PEA) but without the facial features of FAS were compared to a group of 41 control participants (mean 12.8 years, 20 females, 21 males). Findings of significant microcephaly and disproportionately reduced basal ganglia volumes in the FAS group were confirmed. Novel findings were that in FAS participants, white matter volumes were more affected than gray matter volumes in the cerebrum, and parietal lobes were more affected than temporal and occipital lobes. Among subcortical structures, in contrast to the disproportionate effects on caudate nucleus, the hippocampus was relatively preserved in FAS participants. Differences between the PEA group and controls were generally non-significant; however, among a few of the structures most affected in FAS participants, there was some evidence for volume reduction in PEA participants as well, specifically in basal ganglia and the parietal lobe. There were no group differences in cerebral volume asymmetries. Severe prenatal alcohol exposure appears to produce a specific pattern of brain hypoplasia. [source] Abnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT-deficiency)DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2000László Sztriha MD PhD The case of a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphateacyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Deficient de novo plasmalogen synthesis in her fibroblasts as a result of low DHAPAT activity was found, while her very-long-chain fatty acid profile, phytanic acid concentration, alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase) activity, and peroxisomal 3-ketoacyl-CoA thiolase protein were normal. A mutation in her DHAPAT complementary DNA resulted in the substitution of an arginine residue in the protein at position 211 by a histidine (R211H). Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. DHAPAT and alkyl-DHAP synthase initiate the synthesis of plasmalogens, which are major constituents of myelin phospholipids. The reported girl's abnormal formation of myelin is probably related to the inadequacy of plasmalogen biosynthesis, which is likely to be due to deficient DHAPAT activity. [source] Cross-sectional analysis of the association between age and corpus callosum size in chimpanzees (Pan troglodytes)DEVELOPMENTAL PSYCHOBIOLOGY, Issue 2 2010William D. Hopkins Abstract The CC is the major white matter tract connecting the cerebral hemispheres and provides for interhemispheric integration of sensory, motor and higher-order cognitive information. The midsagittal area of the CC has been frequently used as a marker of brain development in humans. We report the first investigation into the development of the corpus callosum and its regional subdivisions in chimpanzees (Pan troglodytes). Magnetic resonance images were collected from 104 chimpanzees (female n,=,63, male n,=,41) ranging in age from 6 years (pre-pubescent period) to 54 years (old age). Sustained linear growth was observed in the area of the CC subdivision of the genu; areas of the posterior midbody and anterior midbody displayed nonlinear growth during development. After adjusting for total brain size, we observed linear growth trajectories of the total CC and CC subdivisions of the genu, posterior midbody, isthmus and splenium, and nonlinear growth trajectories of the rostral body and anterior midbody. These developmental patterns are similar to the development of the CC in humans. As the growth curves of the CC mirrors growth seen in the percentage of white matter in humans, our results suggest chimpanzees show continued white matter development in regions related to cognitive development. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:133,141, 2010 [source] Ictal Pattern of EEG and Muscular Activation in Symptomatic Infantile Spasms: A Videopolygraphic and Computer AnalysisEPILEPSIA, Issue 12 2002Francesca Bisulli Summary: ,Purpose: To investigate ictal muscular phenomena characterizing symptomatic infantile spasms (ISs) and their relation to ictal EEG. Methods: Four children with severe encephalopathy, neurologic impairment, and refractory ISs related to different dysplastic lesions, underwent videopolygraphic recordings collecting surface electromyogram (EMG) activity from several cranial and limb muscles to evaluate the pattern of muscular recruitment, duration, and side-to-side asymmetry of ISs. Acquired data were stored for off-line analysis by a computerized polygraphic system. Results: Spasms were characterized by a complex pattern of muscular activation. A constant or rostrocaudal propagation pattern was lacking in all patients. Intervals between the onset of EMG activity in different muscles in each spasm were very long: ,100,200 ms. Two patients, with hemispheric cortical dysplasia and agenesis of the corpus callosum, had asymmetric and asynchronous spasms in which the EMG onset of the muscles contralateral to the affected hemisphere constantly anticipated that of the ipsilateral ones. Backaveraging of EEG activity disclosed a high-amplitude EEG complex on the same side as the dysplastic lesion, preceding or succeeding the contralateral muscle activity onset. In the other two patients with diffuse cortical dysplasia, no EEG transient was related to EMG activity onset. Conclusions: Despite clinical similarity between spasms in the same patient, our data demonstrate the complexity and heterogeneity of these motor phenomena. Our findings cannot be explained simply in terms of cortical or reticular generators like other motor phenomena such as cortical myoclonus or startle reflex. [source] Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2009M. L. F. Balthazar Background:, Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned. Methods:, We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls. Results:, Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices. Discussion:, We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD. [source] Cerebral blood flow in patients with diffuse axonal injury , examination of the easy Z -score imaging system utilityEUROPEAN JOURNAL OF NEUROLOGY, Issue 5 2007T. Okamoto To evaluate the utility of easy Z -score imaging system (eZIS) in 27 diffuse axonal injury (DAI) cases. Twenty-seven DAI patients were examined with an magnetic resonance imaging (MRI) T2* sequence and with eZIS (seven women, 20 men; age range, 19,35 years; median age: 26.6 years). In this investigation, we excluded patients who exhibited complications such as acute subdural hematoma, acute epidural hematoma, intracerebral hematoma, or brain contusion. We examined the neuropsychological tests and correlated with findings from MRI/eZIS. Furthermore, we evaluated the degree of ventricular enlargement in the bifrontal cerebroventricular index (CVI). Patients were divided into two groups: the enlargement group (bifrontal CVI > 35%, 12 patients) and the non-enlargement group (bifrontal CVI < 35%, 15 patients). All of the patients showed cognitive deficits as observed from the neuropsycological test results. Fifteen out of 27 patients by MRI T1/T2 weighted images and fluid attenuated inversion recovery (FLAIR), 22 out of 27 patients by MRI T2* weighted images and 24 out of 27 patients by eZIS showed abnormal findings. In MRI T2* weighted imaging, the white matter from the frontal lobe, corpus callosum, and brainstem showed abnormal findings. With eZIS, 22 patients (81.5%) showed blood flow degradation in the frontal lobe, and 12 patients (44.4%) in cingulate gyrus. In the enlargement group, Functional Independence Measure, Mini-Mental State Examination, Verbal IQ (VIQ)/Full Scale IQ (FIQ), Trail Making Test-B (TMT-B), and Non-paired of Miyake Paired Test were significantly lower. Amongst 12 patients without ventricular enlargement who had no abnormal findings in MRI T1/T2 weighted images and FLAIR, abnormal findings were detectable in seven patients with MRI T2* weighted imaging and to 10 patients with eZIS. Results of the MRI examination alone cannot fully explain DAI frontal lobe dysfunction. However, addition of the eZIS-assisted analysis derived from the single photon emission computed tomography (SPECT) data enabled us to understand regions where blood flow was decreased, i.e., where neuronal functions conceivably might be reduced. [source] Extensive neuroimaging of a transient lesion in the splenium of the corpus callosumEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2007H. Shimizu No abstract is available for this article. [source] Marchiafava,Bignami disease: two cases with favourable outcomeEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2001J. Helenius Marchiafava,Bignami disease (MBD) is a rare disorder of an unknown aetiology but strongly associated with alcoholism. MBD primarily affects the corpus callosum leading to confusion, dysarthria, seizures and frequently to death. Over 250 cases from all races and from almost all nationalities have been reported, most cases being alcoholics. We report two cases with a favourable outcome. Magnetic resonance imaging (MRI) demonstrated a typical lesion of the corpus callosum, in both patients. The patients, a 44-year-old male and a 40-year-old female, presented with depressed consciousness and a variety of other symptoms, but finally made a reasonably good recovery leading to home discharge. To the best of our knowledge, only one additional case of MBD from Scandinavia has been published. As alcoholism is a major public health problem in Scandinavia, we assume that MBD is underdiagnosed and/or under-reported. Non-specific general symptoms and encephalopathy in an alcoholic may harbour undiagnosed MBD. We suggest that the incidence of MBD may be higher and its prognosis may be milder than generally believed. [source] Callosal contribution to ocular dominance in rat primary visual cortexEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Chiara Cerri Abstract Ocular dominance (OD) plasticity triggered by monocular eyelid suture is a classic paradigm for studying experience-dependent changes in neural connectivity. Recently, rodents have become the most popular model for studies of OD plasticity. It is therefore important to determine how OD is determined in the rodent primary visual cortex. In particular, cortical cells receive considerable inputs from the contralateral hemisphere via callosal axons, but the role of these connections in controlling eye preference remains controversial. Here we have examined the role of callosal connections in binocularity of the visual cortex in naďve young rats. We recorded cortical responses evoked by stimulation of each eye before and after acute silencing, via stereotaxic tetrodotoxin (TTX) injection, of the lateral geniculate nucleus ipsilateral to the recording site. This protocol allowed us to isolate visual responses transmitted via the corpus callosum. Cortical binocularity was assessed by visual evoked potential (VEP) and single-unit recordings. We found that acute silencing of afferent geniculocortical input produced a very significant reduction in the contralateral-to-ipsilateral (C/I) VEP ratio, and a marked shift towards the ipsilateral eye in the OD distribution of cortical cells. Analysis of absolute strength of each eye indicated a dramatic decrease in contralateral eye responses following TTX, while those of the ipsilateral eye were reduced but maintained a more evident input. We conclude that callosal connections contribute to normal OD mainly by carrying visual input from the ipsilateral eye. These data have important implications for the interpretation of OD plasticity following alterations of visual experience. [source] Absence of hematopoiesis from transplanted olfactory bulb neural stem cellsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004María J. Yusta-Boyo Abstract Neural stem cells giving rise to neurons and glia cells have been isolated from the embryonic and adult central nervous system. The extent to which they are able to differentiate into cells of non-neural lineages, such as the hematopoietic lineage, is nonetheless unclear. We previously reported the isolation of stem cells from the mouse olfactory bulb neuroepithelium. In the present study, we analysed whether olfactory bulb stem cells (OBSC) can generate cells with hematopoietic features. Cells were prepared from the olfactory bulbs of transgenic mice expressing enhanced green fluorescent protein (EGFP). In culture, transgenic cells proliferated with the same kinetics as wild-type cells. Following mitogen removal, both cell types gave rise to similar numbers of neurons, astrocytes and oligodendrocytes, indicating that EGFP overexpression does not alter OBSC proliferation and differentiation patterns. When these cells were injected into the tail vein of irradiated mice, no hematopoietic cells derived from the OBSC could be recovered in their peripheral blood, spleen or bone marrow. By contrast, when OBSC were transplanted into the adult brain, EGFP-positive cells were found in the striatum and corpus callosum; differentiated cells expressed antigenic markers of neurons and astrocytes. These results suggest that embryonic olfactory bulb stem cells are not endowed with the potential to produce hematopoiesis. [source] Impairment of binocular vision in the adult cat induces plastic changes in the callosal cortical mapEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2001Laurent Watroba Abstract In the primary visual cortex of normally reared adult cat, neurons activated through the corpus callosum are almost entirely located at the 17/18 border. They display small receptive fields distributed along the central vertical meridian of the visual field and are orientation selective. Here we demonstrate that a few weeks of monocular deprivation or unilateral convergent strabismus produced in adulthood does not modify the cortical distribution of these neurons, but leads to an increase of their receptive field size mainly toward the ipsilateral hemifield and to a loss of their orientation selectivity. We conclude that manipulation of binocular vision in the adult modifies neither the location of the primary callosal cortical map nor its retinotopy. In contrast, it induces functional plastic changes in this map which lead to a significant widening of the area of visual space signalled through the corpus callosum. These plastic changes are interpreted as the result of the strengthening of normally hidden subthreshold synaptic inputs. [source] Deficiency of electroneutral K+,Cl, cotransporter 3 causes a disruption in impulse propagation along peripheral nervesGLIA, Issue 13 2010Yuan-Ting Sun Abstract Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K+,Cl, cotransporter (KCC) family includes four isoforms (KCC1,4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K+ and Cl, with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2,4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na+,K+,2Cl, -cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3,/, mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3,/, mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K+,Cl, cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. © 2010 Wiley-Liss, Inc. [source] Adult-onset deficiency in growth hormone and insulin-like growth factor-I alters oligodendrocyte turnover in the corpus callosumGLIA, Issue 10 2009Kun Hua Abstract Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis influences glial turnover in the normal adult brain. In the current study, we used a selective model of adult-onset GH and IGF-I deficiency to evaluate the role of GH and IGF-I in regulating glial proliferation and survival in the adult corpus callosum. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete via twice daily injections of GH starting at postnatal day 28 (P28), approximately the age at which GH pulse amplitude increases in developing rodents. GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Quantitative analyses revealed that adult-onset GH/IGF-I deficiency decreased cell proliferation in the white matter and decreased the survival of newborn oligodendrocytes. These findings are consistent with the hypothesis that aging-related changes in the GH/IGF-I axis produce deficits in ongoing turnover of oligodendrocytes, which may contribute to aging-related cognitive changes and deficits in remyelination after injury. © 2008 Wiley-Liss, Inc. [source] Monocyte chemoattractant protein-1 (MCP-1) produced via NF-,B signaling pathway mediates migration of amoeboid microglia in the periventricular white matter in hypoxic neonatal ratsGLIA, Issue 6 2009Y. Y. Deng Abstract Monocyte chemoattractant protein-1 (MCP-1), a member of ,-chemokine subfamily, regulates the migration of microglia, monocytes, and lymphocytes to the inflammatory site in the central nervous system. We sought to determine if amoeboid microglial cells (AMC) produce MCP-1 that may be linked to migration of AMC in the corpus callosum periventricular white matter in hypoxic neonatal rats. A striking feature in 1-day-old rats subjected to hypoxia was a marked increase in cell numbers of AMC and immunoexpression of MCP-1 and its receptor (CCR2). By BrdU immunostaining, there was no significant change in the proliferation rate of AMC after hypoxic exposure when compared with the corresponding control rats. When injected intracerebrally into the corpus callosum of 7-day-old postnatal rats, MCP-1 induced the chemotactic migration of AMC to the injection site. In primary microglial cell culture subjected to hypoxia, there was a significant increase in MCP-1 release involving NF-,B signaling pathway. In in vitro chemotaxis assay, the medium derived from hypoxia-treated microglial cultures attracted more migratory microglial cells than that from the control microglial culture. The present results suggest that following a hypoxic insult, AMC in the neonatal rats increase MCP-1 production via NF-,B signaling pathway. This induces the migration and accumulation of AMC from the neighboring areas to the periventricular white matter (PWM). It is concluded that the preponderance and active migration of AMC, as well as them being the main cellular source of MCP-1, may offer an explanation for the PWM being susceptible to hypoxic damage in neonatal brain. © 2008 Wiley-Liss, Inc. [source] Identification of Tmem10/Opalin as an oligodendrocyte enriched gene using expression profiling combined with genetic cell ablationGLIA, Issue 11 2008Neev Golan Abstract Oligodendrocytes form an insulating multilamellar structure of compact myelin around axons, which allows efficient and rapid propagation of action potentials. However, little is known about the molecular mechanisms operating at the onset of myelination and during maintenance of the myelin sheath in the adult. Here we use a genetic cell ablation approach combined with Affymetrix GeneChip microarrays to identify a number of oligodendrocyte-enriched genes that may play a key role in myelination. One of the "oligogenes" we cloned using this approach is Tmem10/Opalin, which encodes for a novel transmembrane glycoprotein. In situ hybridization and RT-PCR analysis revealed that Tmem10 is selectively expressed by oligodendrocytes and that its expression is induced during their differentiation. Developmental immunofluorescence analysis demonstrated that Tmem10 starts to be expressed in the white matter tracks of the cerebellum and the corpus callosum at the onset of myelination after the appearance of other myelin genes such as MBP. In contrast to the spinal cord and brain, Tmem10 was not detected in myelinating Schwann cells, indicating that it is a CNS-specific myelin protein. In mature oligodendrocytes, Tmem10 was present at the cell soma and processes, as well as along myelinated internodes, where it was occasionally concentrated at the paranodes. In myelinating spinal cord cultures, Tmem10 was detected in MBP-positive cellular processes that were aligned with underlying axons before myelination commenced. These results suggest a possible role of Tmem10 in oligodendrocyte differentiation and CNS myelination. © 2008 Wiley-Liss, Inc. [source] Astrocyte-specific expression of a soluble form of the murine complement control protein Crry confers demyelination protection in the cuprizone modelGLIA, Issue 14 2007Dustin T. Briggs Abstract Complement has been implicated as a potential effector mechanism in neurodegeneration; yet the precise role of complement in this process remains elusive. In this report, we have utilized the cuprizone model of demyelination-remyelination to examine the contribution of complement to disease. C1q deposition was observed in the corpus callosum of C57BL/6 mice during demyelination, suggesting complement activation by apoptotic oligodendrocyte debris. Simultaneously, these mice lost expression of the rodent complement regulatory protein, Crry. A soluble CNS-specific form of the Crry protein (sCrry) expressed in a transgenic mouse under the control of an astrocyte-specific promoter was induced in the corpus callosum during cuprizone treatment. Expression of this protein completely protected the mice from demyelination. Interestingly, sCrry mice had low levels of demyelination at later times when control mice were remyelinating. Although the sCrry transgenic mice had lower levels of demyelination, there was no decrease in overall cellularity, however there were decreased numbers of microglia in the sCrry mice relative to controls. Strikingly, sCrry mice had early recovery of mature oligodendrocytes, although they later disappeared. TUNEL staining suggested that production of the sCrry protein in the transgenic mice protected from a late apoptosis event at 3 weeks of cuprizone treatment. Our data suggest complement provides some protection of mature oligodendrocytes during cuprizone treatment but may be critical for subsequent remyelination events. These data suggest that temporal restriction of complement inhibition may be required in some disease settings. © 2007 Wiley-Liss, Inc. [source] Transient expression of endothelins in the amoeboid microglial cells in the developing rat brainGLIA, Issue 6 2006Chun-Yun Wu Abstract Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1 (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in large numbers at birth, but were progressively reduced with age and were undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression in AMC was reduced but the incidence of apoptotic cells was not increased when compared with the control suggesting that this was due to its downregulation that may help regulate the constriction of blood vessels bearing ET-A receptor. AMC were endowed ET-B receptor indicating that ET released by the cells may also act via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1 mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however, remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed to its upregulated expression in vitro may be due to the complexity of the brain tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and OGD treatments may be due to different signaling pathways independently regulating the two isoforms. The present novel finding has added microglia as a new cellular source of ET that may take part in multiple functions including regulating vascular constriction and chemokines release. © 2006 Wiley-Liss, Inc. [source] Heritability of hippocampal size in elderly twin men: Equivalent influence from genes and environmentHIPPOCAMPUS, Issue 6 2001Edith V. Sullivan Abstract Recent studies have established that environmental factors can modify hippocampal structure and enhance function in adult rodents, but the extent to which genes and the environment exert differential contributions to hippocampal structural integrity in humans is unknown. Here, we applied the twin model in a large sample of elderly twin men to examine in late life the balance of environmental and genetic effects on the size of the hippocampus in comparison with other brain structures. This study provides novel evidence that the volume of the hippocampus, as measured on MRI, is subject to substantially less genetic control than are comparison brain regions also measured: temporal horn volume, midsagittal area of the corpus callosum, and intracranial volume (ICV). In particular, about 60% of the temporal horn variance and 80% of the callosal and ICV variance was attributable to genetic influences, whereas only 40% of the hippocampal variance was attributable to genetic influences. These results suggest that environment, whether by itself or in interaction with genes, has the potential of exerting greater and possibly longer control in modifying hippocampal size than other brain regions that are under greater genetic control. Considering the potential of environmental modification of this structure suggested by lower heritability, the hippocampus appears well-suited to support the dynamic processes of encoding and consolidation of new, declarataive memories. Hippocampus 2001;11:754,762. © 2001 Wiley-Liss, Inc. [source] A multiparametric evaluation of regional brain damage in patients with primary progressive multiple sclerosisHUMAN BRAIN MAPPING, Issue 9 2009Antonia Ceccarelli Abstract The purpose of this study is to define the topographical distribution of gray matter (GM) and white matter (WM) damage in patients with primary progressive multiple sclerosis (PPMS), using a multiparametric MR-based approach. Using a 3 Tesla scanner, dual-echo, 3D fast-field echo (FFE), and diffusion tensor (DT) MRI scans were acquired from 18 PPMS patients and 17 matched healthy volunteers. An optimized voxel-based (VB) analysis was used to investigate the patterns of regional GM density changes and to quantify GM and WM diffusivity alterations of the entire brain. In PPMS patients, GM atrophy was found in the thalami and the right insula, while mean diffusivity (MD) changes involved several cortical-subcortical structures in all cerebral lobes and the cerebellum. An overlap between decreased WM fractional anisotropy (FA) and increased WM MD was found in the corpus callosum, the cingulate gyrus, the left short temporal fibers, the right short frontal fibers, the optic radiations, and the middle cerebellar peduncles. Selective MD increase, not associated with FA decrease, was found in the internal capsules, the corticospinal tracts, the superior longitudinal fasciculi, the fronto-occipital fasciculi, and the right cerebral peduncle. A discrepancy was found between regional WM diffusivity changes and focal lesions because several areas had DT MRI abnormalities but did not harbor T2-visible lesions. Our study allowed to detect tissue damage in brain areas associated with motor and cognitive functions, which are known to be impaired in PPMS patients. Combining regional measures derived from different MR modalities may be a valuable tool to improve our understanding of PPMS pathophysiology. Hum Brain Mapp 2009. © 2009 Wiley-Liss, Inc. [source] Heritability of regional and global brain structure at the onset of puberty: A magnetic resonance imaging study in 9-year-old twin pairsHUMAN BRAIN MAPPING, Issue 7 2009Jiska S. Peper Abstract Puberty represents the phase of sexual maturity, signaling the change from childhood into adulthood. During childhood and adolescence, prominent changes take place in the brain. Recently, variation in frontal, temporal, and parietal areas was found to be under varying genetic control between 5 and 19 years of age. However, at the onset of puberty, the extent to which variation in brain structures is influenced by genetic factors (heritability) is not known. Moreover, whether a direct link between human pubertal development and brain structure exists has not been studied. Here, we studied the heritability of brain structures at 9 years of age in 107 monozygotic and dizygotic twin pairs (N = 210 individuals) using volumetric MRI and voxel-based morphometry. Children showing the first signs of secondary sexual characteristics (N = 47 individuals) were compared with children without these signs, based on Tanner-stages. High heritabilities of intracranial, total brain, cerebellum, and gray and white matter volumes (up to 91%) were found. Regionally, the posterior fronto-occipital, corpus callosum, and superior longitudinal fascicles (up to 93%), and the amygdala, superior frontal and middle temporal cortices (up to 83%) were significantly heritable. The onset of secondary sexual characteristics of puberty was associated with decreased frontal and parietal gray matter densities. Thus, in 9-year-old children, global brain volumes, white matter density in fronto-occipital and superior longitudinal fascicles, and gray matter density of (pre-)frontal and temporal areas are highly heritable. Pubertal development may be directly involved in the decreases in gray matter areas that accompany the transition of our brains from childhood into adulthood. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion,HUMAN MUTATION, Issue 3 2009Paola S. Denora Abstract Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing. © 2008 Wiley-Liss, Inc. [source] ZFHX1B mutations in patients with Mowat-Wilson syndrome,HUMAN MUTATION, Issue 4 2007Florence Dastot-Le Moal Abstract Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)-multiple congenital anomaly syndrome, characterized by typical facies, severe MR, epilepsy, and variable congenital malformations, including Hirschsprung disease (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the corpus callosum (ACC). It is caused by de novo heterozygous mutations or deletions of the ZFHX1B gene located at 2q22. ZFHX1B encodes Smad-interacting protein-1 (SMADIP1 or SIP1), a transcriptional corepressor involved in the transforming growth factor-, signaling pathway. It is a highly evolutionarily conserved gene, widely expressed in embryological development. Over 100 mutations have been described in patients with clinically typical MWS, who almost always have whole gene deletions or truncating mutations (nonsense or frameshift) of ZFHX1B, suggesting that haploinsufficiency is the basis of MWS pathology. No obvious genotype,phenotype correlation could be identified so far, but atypical phenotypes have been reported with missense or splice mutations in the ZFHX1B gene. In this work we describe 40 novel mutations and we summarize the various mutational reports published since the identification of the causative gene. Hum Mutat 28(4), 313,321, 2007. © 2007 Wiley-Liss, Inc. [source] Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM geneHUMAN MUTATION, Issue 1 2001Sabine Weller Abstract L1 disease is a group of overlapping clinical phenotypes including X-linked hydrocephalus, MASA syndrome, spastic paraparesis type 1, and X-linked agenesis of corpus callosum. The patients are characterized by hydrocephalus, agenesis or hypoplasia of corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia, and adducted thumbs. The responsible gene, L1CAM, encodes the L1 protein which is a member of the immunoglobulin superfamily of neuronal cell adhesion molecules. The L1 protein is expressed in neurons and Schwann cells and seems to be essential for nervous system development and function. The patients' gene mutations are distributed over the functional protein domains. The exact mechanisms by which these mutations cause a loss of L1 protein function are unknown. There appears to be a relationship between the patients' clinical phenotype and the genotype. Missense mutations in extracellular domains or mutations in cytoplasmic regions cause milder phenotypes than those leading to truncation in extracellular domains or to non-detectable L1 protein. Diagnosis of patients and carriers, including prenatal testing, is based on the characteristic clinical picture and DNA mutation analyses. At present, there is no therapy for the prevention or cure of patients' neurological disabilities. Hum Mutat 18:1,12, 2001. © 2001 Wiley-Liss, Inc. [source] Detecting corpus callosum abnormalities in autism subtype using planar conformal mappingINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING, Issue 2 2010Ye Duan Abstract A number of studies have documented that autism has a neurobiological basis, but the anatomical extent of these neurobiological abnormalities is largely unknown. In this paper, we apply advanced computational techniques to extract 3D models of the corpus callosum (CC) and subsequently analyze local shape variations in a homogeneous group of autistic children. Besides the traditional volumetric analysis, we explore additional phenotypic traits based on the oriented bounding rectangle of the CC. In shape analysis, a new conformal parameterization is applied in our shape analysis work, which maps the surface onto a planar domain. Surface matching among different individual meshes is achieved by aligning the planar domains of individual meshes. Shape differences of the CC between autistic patients and the controls are computed using Hotelling T2 two-sample metric followed by a permutation test. The raw and corrected p -values are shown in the results. Additional visualization of the group difference is provided via mean difference map. Copyright © 2009 John Wiley & Sons, Ltd. [source] A case of nevus comedonicus syndrome associated with neurologic and skeletal abnormalitiesINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2001Young-Joon Seo MD A 12-year-old male was referred to us with recurrent pus discharge from tender nodules on the right axilla dating from the neonatal period. The nodules were black, characterized by scarring with dilated follicular openings and there were black papules filled with comedo-like keratin plugs in both axillae. Physical examination revealed a bowing deformity of the right third finger and retardation in language ability. The patient was referred to the Departments of Neurology and Orthopedics in Chungnam National University Hospital, Korea. Histologic examination of one of the black comedo-like lesions showed a bulbous and dilated infundibulum that contained laminated keratin, indicating a diagnosis of nevus comedonicus. A CT scan of the brain revealed dysgenesis of the corpus callosum. The IQ (intelligence quotient) score of the patient, measured by the Korean Wechsler Intelligence Scale for Children-Revised, was 94. The only difficulty noted for ordinary life was learning language. A radiograph of the right hand revealed hyperextension and an ulnar drift deformity of the right middle finger. Corrective osteotomy with external fixation and an iliac bone autograft were performed. Intermittent neurologic follow-up visits were ordered for the noted language deficit. At present the patient only exhibits difficulty in calculation. Oral antibiotics were administered to the skin lesions on occasion for secondary infections and inflammation of the cysts and comedones. Extraction of the comedones was performed as needed. [source] | |||||||||||||||||||||||||||||||||||||