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Cortical Development (cortical + development)

Distribution by Scientific Domains

Medical Sciences	48%
Life Sciences	42%
2 Other Domains	10%

Selected Abstracts

Mechanisms of Epileptogenesis in Tuberous Sclerosis Complex and Related Malformations of Cortical Development with Abnormal Glioneuronal Proliferation

EPILEPSIA, Issue 1 2008
Michael Wong
Summary Malformations of cortical development (MCDs) are increasingly recognized as causes of medically intractable epilepsy. In order to develop more effective, rational therapies for refractory epilepsy related to MCDs, it is important to achieve a better understanding of the underlying mechanisms of epileptogenesis, but this is complicated by the wide variety of different radiographic, histopathological, and molecular features of these disorders. A subset of MCDs share a number of characteristic cellular and molecular abnormalities due to early defects in neuronal and glial proliferation and differentiation and have a particularly high incidence of epilepsy, suggesting that this category of MCDs with abnormal glioneuronal proliferation may also share a common set of primary mechanisms of epileptogenesis. This review critically analyzes both clinical and basic science evidence for overlapping mechanisms of epileptogenesis in this group of disorders, focusing on tuberous sclerosis complex, focal cortical dysplasia with balloon cells, and gangliogliomas. Specifically, the role of lesional versus perilesional regions, circuit versus cellular/molecular defects, and nonneuronal factors, such as astrocytes, in contributing to epileptogenesis in these MCDs is examined. An improved understanding of these various factors involved in epileptogenesis has direct clinical implications for optimizing current treatments or developing novel therapeutic approaches for epilepsy in these disorders. [source]

A Distinct Asymmetrical Pattern of Cortical Malformation: Large Unilateral Malformation of Cortical Development with Contralateral Periventricular Nodular Heterotopia in Three Pediatric Cases

EPILEPSIA, Issue 8 2005
Annapurna Poduri
Summary:,Purpose: To describe a distinct asymmetrical pattern of cortical malformation with large focal malformations of cortical development (MCDs) and contralateral periventricular nodular heterotopia (PNH). Methods: We identified three patients with epilepsy and focal EEG abnormalities. Each patient underwent 1.5-Tesla magnetic resonance imaging (MRI) to obtain sagittal T1 -weighted, axial fluid-attenuated inversion recovery (FLAIR), fast spin-echo (FSE) T2 -weighted, and coronal fast spin-echo inversion recovery (FSEIR) T2 -weighted images; coronal spoiled gradient recalled (SPGR) T1 -weighted images were obtained in two cases. Results: Patient 1, an 18-year-old right-handed man, had a 4-year history of intractable seizures. MRI revealed a right frontal subcortical heterotopia (SH) and a single left anterior PNH. Patient 2, a 10-year-old left-handed boy, had a 4-year history of epilepsy. MRI revealed a large region of SH in the left temporal, parietal, and occipital lobes and three right-sided PNH. Patient 3, a 16-month-old girl, had medically refractory infantile spasms. MRI revealed a large MCD in the left parietal lobe with contiguous underlying periventricular heterotopia as well as a small contralateral PNH. Conclusions: These cases together illustrate a distinct asymmetrical pattern of a large focal MCD with small contralateral PNH. The asymmetrical involvement of the two hemispheres suggests that the stage of maximal disruption of cortical development may differ between the two hemispheres. Further study into the mechanisms underlying such asymmetrical patterns of cortical malformation should enhance our understanding of cortical development as well as hemispheric lateralization. [source]

Subtraction SPECT Coregistered to MRI in Focal Malformations of Cortical Development: Localization of the Epileptogenic Zone in Epilepsy Surgery Candidates

EPILEPSIA, Issue 4 2004
Terence J. O'Brien
Summary: Purpose: To determine the extent to which periictal subtraction single-photon emission computed tomography (SPECT) may improve detection and definition of the epileptogenic zone in patients with focal malformations of cortical development (MCDs). Methods: Subtraction SPECT coregistered to magnetic resonance (MR) images (SISCOM) were constructed for 22 consecutive patients with focal MCDs who underwent periictal SPECT injection (18 ictal and four postictal). In the 17 patients who had epilepsy surgery, concordance between the site of SISCOM localization and site of surgical resection was determined by coregistration of SISCOM images with postoperative MRIs. Results: SISCOM images were localizing in 19 (86%) patients, including eight of the 10 with nonlocalizing MRI. Concordance of SISCOM localization was 91% with MRI localization, 93% with scalp ictal EEG localization, and 100% with intracranial EEG localization. Eight patients whose SISCOM localization was concordant with the surgical resection site had lower postoperative seizure frequency scores (SFSs; p = 0.04) and greater postoperative improvement in SFSs (p = 0.05) than the nine patients whose SISCOM was either nonconcordant or nonlocalizing. On multiple regression analysis, a model combining SISCOM concordance with surgical resection site and extent of MRI lesion resection was predictive of postoperative SFS (R2= 0.47; p = 0.03). Conclusions: Periictal subtraction SPECT using the SISCOM technique provides useful information for seizure localization in patients with focal MCDs, even when MRI is nonlocalizing. [source]

Cortical development in the presenilin-1 null mutant mouse fails after splitting of the preplate and is not due to a failure of reelin-dependent signaling

DEVELOPMENTAL DYNAMICS, Issue 9 2008
Rita De Gasperi
Abstract Cortical development is disrupted in presenilin-1 null mutant (Psen1,/,) mice. Prior studies have commented on similarities between Psen1,/, and reeler mice. Reelin induces phosphorylation of Dab1 and activates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Psen1 is known to modulate PI3K/Akt signaling and both known reelin receptors (apoER2 and VLDLR) are substrates for Psen1 associated ,-secretase activity. The purpose of this study was to determine whether reelin signaling is disrupted in Psen1,/, mice. We show that, while Dab1 is hypophosphorylated late in cortical development in Psen1,/, mice, it is normally phosphorylated at earlier ages and reelin signaling is intact in Psen1,/, primary neuronal cultures. ,-secretase activity was also not required for reelin-induced phosphorylation of Dab1. Unlike reeler mice the preplate splits in Psen1,/, brain. Thus cortical development in Psen1,/, mice fails only after splitting of the preplate and is not due to an intrinsic failure of reelin signaling. Developmental Dynamics 237:2405,2414, 2008. © 2008 Wiley-Liss, Inc. [source]

Advanced microscopic imaging methods to investigate cortical development and the etiology of mental retardation

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2005
Tarik F. Haydar
Abstract Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these events during prenatal development can lead to cognitive dysfunction after birth. Many of underlying causes of mental retardation must therefore be studied in developing brains. To aid in this research, live imaging using laser scanning microscopy (LSM) has recently allowed neuroscientists to delve deeply into the complex three-dimensional environment of the living brain to record dynamic cellular events over time. This review will highlight recent examples of how LSM is being applied to elucidate both normal and abnormal cortical development. © 2005 Wiley-Liss, Inc. MRDD Research Reviews 2005;11:303,316. [source]

Cortical development in the presenilin-1 null mutant mouse fails after splitting of the preplate and is not due to a failure of reelin-dependent signaling

Neuropsychological profile of children with subcortical band heterotopia

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 11 2009
MEGAN SPENCER-SMITH BPSYCSC PHD
Aim, Subcortical band heterotopia (SBH) or ,double cortex' is a malformation of cortical development resulting from impaired neuronal migration. So far, research has focused on the neurological, neuroimaging, and genetic correlates of SBH. More recently, clinical reports and small sample studies have documented neuropsychological dysfunction in patients with this malformation. This study aimed to characterize further the phenotype of patients with SBH by describing the neuropsychological profiles of children. Method, Seven children (six females) aged 4 to 15 years were assessed for cognitive functioning (intellectual ability, processing speed, attention, working memory) and academic achievement (reading, spelling, arithmetic). Parents completed questionnaires examining their child's social skills and problem behaviours. Magnetic resonance images (MRI) conducted for routine clinical follow-up were coded by a paediatric neurologist. Genetic and seizure history were obtained from medical records. Results, There was variation in the neurological, neuroimaging, and genetic presentation of children in the sample. Impairments were observed in all areas of neuropsychological functioning examined. Intellectual ability was generally within the ,extremely low' range (full-scale IQ 44,74; performance IQ 45,72; verbal IQ 57,80). Generalized impairments in cognitive skills were typical, with severe impairments (scores greater than 2SD below the test mean) reported in processing speed, working memory, and arithmetic. Impairments in academic, social, and behavioural functioning were less generalized. No clear relationship between neuroimaging and neuropsychological impairments was found. Interpretation, Children with SBH demonstrate cognitive, academic, social, and behavioural problems, with the greatest difficulties in processing speed and complex cognitive skills. [source]

Type 1 diabetes and epilepsy: Efficacy and safety of the ketogenic diet

EPILEPSIA, Issue 6 2010
Anastasia Dressler
Summary Diabetes type 1 seems to be more prevalent in epilepsy, and low-carbohydrate diets improve glycemic control in diabetes type 2, but data on the use of the classic ketogenic diet (KD) in epilepsy and diabetes are scarce. We present 15 months of follow-up of a 3 years and 6 months old girl with diabetes type 1 (on the KD), right-sided hemiparesis, and focal epilepsy due to a malformation of cortical development. Although epileptiform activity on electroencephalography (EEG) persisted (especially during sleep), clinically overt seizures have not been reported since the KD. An improved activity level and significant developmental achievements were noticed. Glycosylated hemoglobin (HbA1c) levels improved, and glycemic control was excellent, without severe side effects. Our experience indicates that diabetes does not preclude the use of the KD. [source]

Interobserver and intraobserver reproducibility in focal cortical dysplasia (malformations of cortical development)

EPILEPSIA, Issue 12 2009
Wendy A. Chamberlain
Summary Purpose:, Malformations of cortical development (MCD) (cortical dysplasias) are well-recognized causes of intractable epilepsy. Although a histologic classification system for MCD has been proposed by Palmini et al. (Neurology; 2004; 62:S2), studies to date have not assessed reproducibility. The purpose of this study was to analyze inter- and intraobserver agreement among eight experienced neuropathologists (NPs) with respect to this classification system. Methods:, Sections from 26 epilepsy resections were selected to represent the range of pathologies described by Palmini et al. Recuts of single sections from each case were sent to the NPs to classify. The slides were resent at a later date for reclassification. Kappa analysis for both inter- and intraobserver concordance was performed. Results:, Interobserver agreement was moderate (, = 0.4968). There was ,62.5% (5 of 8 NPs) agreement for 19 of 26 cases. The greatest concordance was present when making focal cortical dysplasia (FCD) types IIA/B classifications (12 of the 14 cases with ,75% consensus). Mild MCD (types I/II) and FCD types IA/B classifications were the least reproducible, and used most frequently in cases without consensus. Intraobserver concordance was moderate to very good (range , = 0.4654,0.8504). The category with the fewest classification changes made on reevaluation was FCD type IIB (4.2%), whereas that with the most changes was mild MCD (types I/II) (52.9%). Discussion:, Interobserver concordance using this approach was moderate. The classification categories with the greatest concordance were FCD type IIA/B, and the least, mild MCD and FCD types IA/B. In addition, difficulty in differentiating Mild MCD/FCD type I lesions from normal and/or gliotic tissue was noted. [source]

Mechanisms of Epileptogenesis in Tuberous Sclerosis Complex and Related Malformations of Cortical Development with Abnormal Glioneuronal Proliferation

Hemispheric Surgery in Children with Refractory Epilepsy: Seizure Outcome, Complications, and Adaptive Function

EPILEPSIA, Issue 1 2007
Sheikh Nigel Basheer
Summary:,Purpose: To describe seizure control, complications, adaptive function and language skills following hemispheric surgery for epilepsy. Methods: Retrospective chart review of patients who underwent hemispheric surgery from July 1993 to June 2004 with a minimum follow-up of 12 months. Results: The study population comprised 24 children, median age at seizure onset six months and median age at surgery 41 months. Etiology included malformations of cortical development (7), infarction (7), Sturge-Weber Syndrome (6), and Rasmussen's encephalitis (4). The most frequent complication was intraoperative bleeding (17 transfused). Age <2 yr, weight <11 kg, and hemidecortication were risk factors for transfusion. Postoperative complications included aseptic meningitis (6), and hydrocephalus (3). At median follow-up of 7 yr, 79% of patients are seizure free. Children with malformations of cortical development and Rasmussen's encephalitis were more likely to have ongoing seizures. Overall adaptive function scores were low, but relative strengths in verbal abilities were observed. Shorter duration of epilepsy prior to surgery was related significantly to better adaptive functioning. Conclusions: Hemispheric surgery is an effective therapy for refractory epilepsy in children. The most common complication was bleeding. Duration of epilepsy prior to surgery is an important factor in determining adaptive outcome. [source]

Event-related fMRI of Myoclonic Jerks Arising from Dysplastic Cortex

EPILEPSIA, Issue 9 2006
John S. Archer
Summary:,Background: Malformations of cortical development can cause epileptiform activity and myoclonic jerks, yet EEG correlates of jerks can be difficult to obtain. Methods: We studied a woman who had frequent episodes of persistent right-foot jerking since childhood. Ictal and interictal EEG had shown no localizing epileptiform activity. Functional imaging experiments were performed with concurrent video monitoring to document the timing of foot jerks. These studies mapped brain regions controlling voluntary right- and left-foot movements, and spontaneous right-foot jerks. Results: High-resolution structural MR imaging revealed a dysplastic gyrus extending anteriorly off the left central sulcus. Event-related analysis of spontaneous jerks revealed prominent activation of the left precentral gyrus (right-foot motor area), bilateral medial frontal regions (supplementary motor area), and the dysplastic gyrus. Hemodynamic response modeling to foot jerks revealed the hemodynamic response peaked earlier in the dysplastic cortex and SMA regions than in the foot area. Discussion: Event-related fMRI in a patient with spontaneous and induced epileptic foot jerks revealed brain regions active during jerks. The results of this analysis allowed us to tailor subsequent intracerebral recordings. Analysis of the timing of the hemodynamic response showed certain brain regions with an earlier rise in BOLD signal, suggesting a possible initiating role, or different hemodynamic response functions. Hemodynamic response timing should be considered carefully when interpreting event-related studies of epileptiform activity. [source]

A Distinct Asymmetrical Pattern of Cortical Malformation: Large Unilateral Malformation of Cortical Development with Contralateral Periventricular Nodular Heterotopia in Three Pediatric Cases

Subtraction SPECT Coregistered to MRI in Focal Malformations of Cortical Development: Localization of the Epileptogenic Zone in Epilepsy Surgery Candidates

Infusion of anti-nerve growth factor into the cisternum magnum of chick embryo leads to decrease cell production in the cerebral cortical germinal epithelium

EUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2007
F. Mashayekhi
There has been considerable recent progress in understanding the processes involved in cerebral cortical development. Several mitogenic and trophic factors have been implicated in the processes of cortical cell proliferation and differentiation. Anti-nerve growth factor (NGF) antibody was administered to 15 days chick foetuses through the cisternum magnum. Control group received phosphate buffered saline (PBS). To identify cells born in the cerebral cortex at the time of antibody or PBS injection, 5,-bromo-2,- deoxyuridine was administered to the foetuses by intravenous injection into an outlying vein using micromanipulation. After injection, the foetuses were re-incubated for another 3 days. All the foetuses were collected on day 18, the brains fixed in paraformaldehyde, cut with a microtome and stained with methyl green pyronin and anti-NGF antibody. Quantitative measurements showed that the thickness of the germinal epithelium (GE) and cerebral cortex in the anti-NGF antibody injected foetuses was decreased when compared with normal control embryos. The number of cells produced in the GE of antibody injected foetuses was decreased when compared with normal control embryos. The results from this study using neutralizing antibody suggests that NGF is an important factor in cerebral cortical development, stimulating neuronal precursor proliferation. [source]

Endothelial cell-derived bone morphogenetic proteins regulate glial differentiation of cortical progenitors

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2008
Tetsuya Imura
Abstract Gliogenesis is an important component of cortical development during the postnatal period. Two macroglial cells are generated in a particular order, i.e. astrocytes first and oligodendrocytes later. The mechanisms underlying this sequence of glial differentiation are unknown but interactions with blood vessels are postulated to play a role. We show, using a mouse in-vitro coculture system, that endothelial cells promote astrocyte differentiation but inhibit oligodendrocyte differentiation of postnatal cortical progenitors. Endothelial cells produce bone morphogenetic proteins (BMPs) to activate Sma- and Mad-related protein (Smad) signalling in progenitors and the effects of endothelial cells on glial differentiation are blocked by the BMP antagonist Noggin. Differentiation of progenitors into astrocytes results in the inhibition of endothelial cell growth, accompanied by changes in gene expression of angiogenic factors, indicating bidirectional interactions between progenitors and endothelial cells. In vivo, Smad signalling is activated in various types of cortical cells including progenitors in association with astrogenesis but is inactivated before the peak of oligodendrogenesis. Capillary vessels isolated from the developing cortex express high levels of BMPs. Together, these results demonstrate that endothelial cells regulate glial differentiation by secreting BMPs in vitro and suggest a similar role in cortical gliogenesis in vivo. [source]

Visualization of corticofugal projections during early cortical development in a ,-GFP-transgenic mouse

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2007
Erin C. Jacobs
Abstract The first postmitotic neurons in the developing neocortex establish the preplate layer. These early-born neurons have a significant influence on the circuitry of the developing cortex. However, the exact timing and trajectory of their projections, between cortical hemispheres and intra- and extra-cortical regions, remain unresolved. Here, we describe the creation of a transgenic mouse using a 1.3 kb golli promoter element of the myelin basic protein gene to target expression of a ,,green fluorescent protein (GFP) fusion protein in the cell bodies and processes of pioneer cortical neurons. During embryonic and early neonatal development, the timing and patterning of process extension from these neurons was examined. Analysis of ,-GFP fluorescent fibers revealed that progression of early labeled projections was interrupted unexpectedly by transient pauses at the corticostriatal and telencephalic,diencephalic boundaries before invading the thalamus just prior to birth. After birth the pioneering projections differentially invaded the thalamus, excluding some nuclei, e.g. medial and lateral geniculate, until postnatal days 10,14. Early labeled projections were also found to cross to the contralateral hemisphere as well as to the superior colliculus. These results indicate that early corticothalamic projections appear to pause before invading specific subcortical regions during development, that there is developmental regulation of innervation of individual thalamic nuclei, and that these early-generated neurons also establish early projections to commissural and subcortical targets. [source]

Foreword to reviews on molecular and cellular basis of cortical development (CONCORDE)

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006
Zoltán Molnár
No abstract is available for this article. [source]

Identification of ventricular-side-enriched molecules regulated in a stage-dependent manner during cerebral cortical development

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006
Itsuki Ajioka
Abstract Radial glial cells are the main component of the embryonic cortical ventricular zone (VZ), producing deep-layer excitatory neurons in the early stage and upper-layer excitatory neurons in the late stage of development. Previous studies have suggested that the laminar fate of deep-layer neurons might be determined by early-stage-specific secretory or transmembrane molecules (S/TMs) in the VZ. However, the different properties required to produce the different types of neurons in early-stage and late-stage VZ cells are largely unknown. Herein, we investigated the stage-dependent transcriptional profiles of the ventricular side of the mouse cortex, which was manually dissected at embryonic day (E)12, E14 and E16, and identified 3985 ,VZ-enriched' genes, regulated stage-dependently, by GeneChip analysis. These molecules were classified into nine types based on stage-dependent regulation patterns. Prediction programs for the S/TMs revealed 659 ,VZ-enriched' S/TMs. In situ hybridization and real-time PCR analysis for several of these molecules showed results consistent with the statistical analysis of the GeneChip experiments. Moreover, we identified 17 cell cycle-related early-stage and ,VZ-enriched' molecules. These molecules included not only those involved in cell cycle progression, but also essential molecules for DNA double-strand break repair, such as Rad51 and Rpa1. These results suggest that the early stage-VZ cells, which produce both deep- and upper-layer neurons, and the late-stage VZ cells, which produce only upper-layer neurons, are intrinsically different. The gene lists presented here will be useful for the investigation of stage-dependent changes in VZ cells and their regulatory mechanisms in the developing cortex. [source]

Neuroimaging of cortical development and brain connectivity in human newborns and animal models

JOURNAL OF ANATOMY, Issue 4 2010
Gregory A. Lodygensky
Abstract Significant human brain growth occurs during the third trimester, with a doubling of whole brain volume and a fourfold increase of cortical gray matter volume. This is also the time period during which cortical folding and gyrification take place. Conditions such as intrauterine growth restriction, prematurity and cerebral white matter injury have been shown to affect brain growth including specific structures such as the hippocampus, with subsequent potentially permanent functional consequences. The use of 3D magnetic resonance imaging (MRI) and dedicated postprocessing tools to measure brain tissue volumes (cerebral cortical gray matter, white matter), surface and sulcation index can elucidate phenotypes associated with early behavior development. The use of diffusion tensor imaging can further help in assessing microstructural changes within the cerebral white matter and the establishment of brain connectivity. Finally, the use of functional MRI and resting-state functional MRI connectivity allows exploration of the impact of adverse conditions on functional brain connectivity in vivo. Results from studies using these methods have for the first time illustrated the structural impact of antenatal conditions and neonatal intensive care on the functional brain deficits observed after premature birth. In order to study the pathophysiology of these adverse conditions, MRI has also been used in conjunction with histology in animal models of injury in the immature brain. Understanding the histological substrate of brain injury seen on MRI provides new insights into the immature brain, mechanisms of injury and their imaging phenotype. [source]

Novel stem/progenitor cells with neuronal differentiation potential reside in the leptomeningeal niche

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009
Francesco Bifari
Abstract Stem cells capable of generating neural differentiated cells are recognized by the expression of nestin and reside in specific regions of the brain, namely, hippocampus, subventricular zone and olfactory bulb. For other brain structures, such as leptomeninges, which contribute to the correct cortex development and functions, there is no evidence so far that they may contain stem/precursor cells. In this work, we show for the first time that nestin-positive cells are present in rat leptomeninges during development up to adulthood. The newly identified nestin-positive cells can be extracted and expanded in vitro both as neurospheres, displaying high similarity with subventricular zone,derived neural stem cells, and as homogeneous cell population with stem cell features. In vitro expanded stem cell population can differentiate with high efficiency into excitable cells with neuronal phenotype and morphology. Once injected into the adult brain, these cells survive and differentiate into neurons, thus showing that their neuronal differentiation potential is operational also in vivo. In conclusion, our data provide evidence that a specific population of immature cells endowed of neuronal differentiation potential is resident in the leptomeninges throughout the life. As leptomeninges cover the entire central nervous system, these findings could have relevant implications for studies on cortical development and for regenerative medicine applied to neurological disorders. [source]

The Freud-1/CC2D1A family: Transcriptional regulators implicated in mental retardation

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2007
Anastasia Rogaeva
Abstract The CC2D1A gene family consists of two homologous genes, Freud-1/CC2D1A and Freud-2/CC2D1B, that share conserved domains, including several DM14 domains that are specific to this protein family, a C-terminal helix-loop-helix domain, and a C2 calcium-dependent phospholipid binding domain. Although the function of Freud-2 is unknown, Freud-1 has been shown to function as a transcriptional repressor of the serotonin-1A receptor gene that binds to a novel DNA element (FRE, 5,-repressor element). The DNA binding and repressor activities of Freud-1 are inhibited by calcium-calmodulin-dependent protein kinase. Recently, a deletion in the CC2D1A gene has been linked to nonsyndromic mental retardation. This deletion results in the truncation of the helix-loop-helix DNA binding and the C2 domains, crucial for Freud-1 repressor activity, and hence is predicted to generate an inactive or weakly dominant negative protein. The possible mechanisms by which inactivation of Freud-1 could lead to abnormal cortical development and cognitive impairment and the potential roles of Freud-1 gene targets are discussed. © 2007 Wiley-Liss, Inc. [source]

Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness

THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2007
Nitin Gogtay
Background:, There are, to date, no pre-post onset longitudinal imaging studies of bipolar disorder at any age. We report the first prospective study of cortical brain development in pediatric bipolar illness for 9 male children, visualized before and after illness onset. Method:, We contrast this pattern with that observed in a matched group of healthy children as well as in a matched group of 8 children with ,atypical psychosis' who had similar initial presentation marked by mood dysregulation and transient psychosis (labeled as ,multi-dimensionally impaired' (MDI)) as in the bipolar group, but have not, to date, developed bipolar illness. Results:, Dynamic maps, reconstructed by applying novel cortical pattern matching algorithms, for the children who became bipolar I showed subtle, regionally specific, bilaterally asymmetrical cortical changes. Cortical GM increased over the left temporal cortex and decreased bilaterally in the anterior (and sub genual) cingulate cortex. This was seen most strikingly after the illness onset, and showed a pattern distinct from that seen in childhood onset schizophrenia. The bipolar neurodevelopmental trajectory was generally shared by the children who remained with MDI diagnosis without converting to bipolar I, suggesting that this pattern of cortical development may reflect affective dysregulation (lability) in general. Conclusions:, These dynamic trajectories of cortical development may explain age-related disparate findings from cross-sectional studies of bipolar illness, and suggest the importance of mood disordered non-bipolar control group in future studies. [source]

Nuclear factor I gene expression in the developing forebrain

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2008
Céline Plachez
Abstract Three members of the Nuclear Factor I (Nfi) gene family of transcription factors; Nfia, Nfib, and Nfix are highly expressed in the developing mouse brain. Nfia and Nfib knockout mice display profound defects in the development of midline glial populations and the development of forebrain commissures (das Neves et al. [1999] Proc Natl Acad Sci U S A 96:11946,11951; Shu et al. [2003] J Neurosci 23:203,212; Steele-Perkins et al. [2005] Mol Cell Biol 25:685,698). These findings suggest that Nfi genes may regulate the substrate over which the commissural axons grow to reach targets in the contralateral hemisphere. However, these genes are also expressed in the cerebral cortex and, thus, it is important to assess whether this expression correlates with a cell-autonomous role in cortical development. Here we detail the protein expression of NFIA and NFIB during embryonic and postnatal mouse forebrain development. We find that both NFIA and NFIB are expressed in the deep cortical layers and subplate prenatally and display dynamic expression patterns postnatally. Both genes are also highly expressed in the developing hippocampus and in the diencephalon. We also find that principally neither NFIA nor NFIB are expressed in callosally projecting neurons postnatally, emphasizing the role for midline glial cell populations in commissure formation. However, a large proportion of laterally projecting neurons express both NFIA and NFIB, indicating a possible cell-autonomous role for these transcription factors in corticospinal neuron development. Collectively, these data suggest that, in addition to regulating the formation of axon guidance substrates, these genes also have cell-autonomous roles in cortical development. J. Comp. Neurol. 508:385,401, 2008. © 2008 Wiley-Liss, Inc. [source]

Patterns of laminins and integrins in the embryonic ventricular zone of the CNS

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 6 2007
Justin D. Lathia
Abstract The extracellular matrix (ECM) provides both a physical framework and a microenvironment that supplies instructive signals from the earliest stages of multicellular development. As a first step toward understanding the role of the ECM in regulating the behavior of neural stem cells (NSCs), here we show the localization of laminins, a heterotrimeric family of ECM molecules expressed in many different stem cell microenvironments, and their corresponding receptors in the embryonic murine ventricular zone (VZ) within which the NSCs undergo symmetrical and asymmetrical divisions required for cortical development. In addition to the presence of laminins containing both the ,2 and ,4 chains, we find distinct patterns of ECM receptor expression in the VZ and in the overlying cortex. Neural stem cells derived from the VZ express high levels of the integrin laminin receptor ,6,1. At developmental stages at which NSCs undergo asymmetrical divisions, integrin ,1 was unevenly distributed in some mitotic pairs at the ventricular wall. These results suggest a significant role in the regulation of NSC fate for laminin/integrin signaling within the microenvironment of the VZ and provide a framework for future molecular and cellular analyses of the role of the ECM in neural development. J. Comp. Neurol. 505:630,643, 2007. © 2007 Wiley-Liss, Inc. [source]

The Epiplasm Gene EPC1 Influences Cell Shape and Cortical Pattern in Tetrahymena thermophila,

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2004
NORMAN E. WILLIAMS
ABSTRACT. The cortical protein Epclp is the most abundant protein in the membrane skeleton, or epiplasm, of Tetrahymena thermophila. A partial sequence of the EPC1 gene was obtained and used to obtain a knockout construct that was successful in transforming Tetrahymena thermophila cells. The results support the conclusion that Epclp influences cell shape and the fidelity of cortical development. It was further observed that this protein is transferred from plus to minus cells during conjugation, and that the imported protein is assembled into the epiplasm of the recipient cell in a discreet series of steps. [source]

From genes to human diseases in cortical development

BIOESSAYS, Issue 7 2007
Gaëlle Friocourt
First page of article [source]

Parenchymal lesions in pharmacoresistant temporal lobe epilepsy: dual and multiple pathology

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005
S. H. Eriksson
Objectives,,, Dual pathology is reported in 5,30% of temporal lobe resections performed in pharmacoresistant epilepsy. Dual pathology may be of importance for surgical planning and also for the understanding of the pathogenesis of epilepsy. We describe the frequency of dual or multiple pathology, i.e. more than one histopathological diagnosis, in adults with temporal lobe resections. Material and Methods,,, Surgical specimens from 33 consecutive patients with resections including mesial as well as neocortical temporal structures were reviewed. All histopathological findings were recorded. Post-mortem specimens from 11 control subjects were also reviewed. Results,,, Dual or multiple pathology was found in almost half of the epilepsy patients (48%). Hippocampal sclerosis was found in 25 patients (76%), malformations of cortical development in 15 (46%), of which 12 (36%) were microdysgenesis, and low-grade tumours in seven (21%). Apart from mild gliosis, there were no histopathological changes in the control specimens. Conclusion,,, Dual or multiple pathology was a common finding in this group of adults with temporal lobe resections. In order to increase our understanding of how aetiological factors may combine in the development of seizures, we consider it relevant and important to report all histopathological findings in epilepsy surgery series. [source]

Herpesviral DNA in brain tissue from patients with temporal lobe epilepsy

ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2004
O. Eeg-Olofsson
Objectives , Presence of DNA from six herpesviruses were examined in brain tissue from patients operated for temporal lobe epilepsy. Material and methods , A total of 19 Canadian patients (I) with a median age of 22 years, 17 Swedish patients (II) with a median age of 14 years and a reference group comprising 12 individuals were studied. Presence of herpesviral DNA was detected by nested polymerase chain reaction. Results , Of three children with Rasmussen's encephalitis, Cytomegalovirus (CMV) DNA was found in two, and human herpesvirus type 6 DNA in two. In six children with ganglioglioma, Epstein,Barr virus (EBV) was detected in four. CMV DNA was found significantly more in group I compared with II, while the reverse occurred with EBV DNA. Malformations of cortical development were found significantly more in group II compared with I. Conclusion , Detection of DNA from some herpesviruses in epileptic brain tissue may possibly be associated with distinct clinical conditions, but factors such as age and malformations of cortical development should also be considered. [source]

Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders

CLINICAL GENETICS, Issue 1 2007
G Di Cristo
GABAergic interneurons powerfully control the function of cortical networks. In addition, they strongly regulate cortical development by modulating several cellular processes such as neuronal proliferation, migration, differentiation and connectivity. Not surprisingly, aberrant development of GABAergic circuits has been implicated in many neurodevelopmental disorders including schizophrenia, autism and Tourette's syndrome. Unfortunately, efforts directed towards the comprehension of the mechanisms regulating GABAergic circuits formation and function have been impaired by the strikingly heterogeneity, both at the morphological and functional level, of GABAergic interneurons. Recent technical advances, including the improvement of interneurons-specific labelling techniques, have started to reveal the basic principles underlying this process. This review summarizes recent findings on the mechanisms underlying the construction of GABAergic circuits in the cortex, with a particular focus on potential implications for brain diseases with neurodevelopmental origin. [source]