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Developing Brain (developing + brain)
Selected AbstractsMechanisms Mediating Oestradiol Modulation of the Developing BrainJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008M. M. McCarthy The brain has been known to be a sensitive target organ for the permanent organisational effects of gonadal steroids for close to 50 years. Recent advances have revealed a variety of unexpected cellular mechanisms by which steroids impact on the synaptic profile of hypothalamic nuclei critical to the control of reproduction. This review focuses on three in particular: 1) prostaglandins in the masculinisation of the preoptic area and control of male sexual behaviour; 2) GABA in the arcuate nucleus and potential control of the anterior pituitary; and 3) non-genomic activation of phosphotydolinositol 3 (PI3) kinase and glutamate in the ventromedial nucleus, which is relevant to the control of female reproductive behaviour. The importance of cell-to-cell communication, be it between neurones or between neurones and astrocytes, is highlighted as an essential principle for expanding the impact of steroids beyond those cells that express nuclear receptors. [source] Timing of Thyroid Hormone Action in the Developing Brain: Clinical Observations and Experimental FindingsJOURNAL OF NEUROENDOCRINOLOGY, Issue 10 2004R. T. Zoeller Abstract The original concept of the critical period of thyroid hormone (TH) action on brain development was proposed to identify the postnatal period during which TH supplement must be provided to a child with congenital hypothyroidism to prevent mental retardation. As neuropsychological tools have become more sensitive, it has become apparent that even mild TH insufficiency in humans can produce measurable deficits in very specific neuropsychological functions, and that the specific consequences of TH deficiency depends on the precise developmental timing of the deficiency. Models of maternal hypothyroidism, hypothyroxinaemia and congential hyperthyroidism have provided these insights. If the TH deficiency occurs early in pregnancy, the offspring display problems in visual attention, visual processing (i.e. acuity and strabismus) and gross motor skills. If it occurs later in pregnancy, children are at additional risk of subnormal visual (i.e. contrast sensitivity) and visuospatial skills, as well as slower response speeds and fine motor deficits. Finally, if TH insufficiency occurs after birth, language and memory skills are most predominantly affected. Although the experimental literature lags behind clinical studies in providing a mechanistic explanation for each of these observations, recent studies confirm that the specific action of TH on brain development depends upon developmental timing, and studies informing us about molecular mechanisms of TH action are generating hypotheses concerning possible mechanisms to account for these pleiotropic actions. [source] The effects of seizures on the connectivity and circuitry of the developing brainDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2004John W. Swann Abstract Recurring seizures in infants and children are often associated with cognitive deficits, but the reason for the learning difficulties is unclear. Recent studies in several animal models suggest that seizures themselves may contribute in important ways to these deficits. Other studies in animals have shown that recurring seizures result in dendritic spine loss. This change, coupled with a down-regulation in NMDA receptor subunit expression, suggests that repetitive seizures may interrupt the normal development of glutamatergic synaptic transmission. We hypothesize that homeostatic, neuroprotective processes are induced by recurring early-life seizures. These processes, by diminishing glutamatergic synaptic transmission, are aimed at preventing the continuation of seizures. However, by preventing the normal development of glutamatergic synapses, and particularly NMDA receptor-mediated synaptic transmission, such homeostatic processes also reduce synaptic plasticity and diminish the ability of neuronal circuits to learn and store memories. MRDD Research Reviews 2004;10:96,100. © 2004 Wiley-Liss, Inc. [source] MRI-based morphometric analysis of typical and atypical brain developmentDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2003David N. Kennedy Abstract The neuroinformatics landscape in which human brain morphometry occurs has advanced dramatically over the past few years. Rapid advancement in image acquisition methods, image analysis tools and interpretation of morphometric results make the study of in vivo anatomic analysis both challenging and rewarding. This has revolutionized our expectations for current and future diagnostic and investigative work with the developing brain. This paper will briefly cover the methods of morphometric analysis that available for neuroanatomic analysis, and tour some sample results from a prototype retrospective database of neuroanatomic volumetric information. From these observations, issues regarding the anatomic variability of developmental maturation of neuroanatomic structures in both typically and atypically developing populations can be discussed. MRDD Research Reviews 2003;9:155,160. © 2003 Wiley-Liss, Inc. [source] Imaging the developing brain with fMRIDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 3 2003M.C. Davidson Abstract Advancements in magnetic imaging techniques have revolutionized our ability to study the developing human brain in vivo. The ability to noninvasively image both anatomy and function in healthy volunteers, including young children, has already enhanced our understanding of brain and behavior relations. The application of these techniques to developmental research offers the opportunity to further explore these relationships and allows us to ask questions about where, when and how cognitive abilities develop in relation to changes in underlying brain systems. It is also possible to explore the contributions of maturation versus learning in the development of these abilities through cross-sectional and longitudinal research involving training and intervention procedures. Current imaging methodologies, in conjunction with new and rapidly evolving techniques, hold the promise of even greater insights into developmental issues in the near future. These methodologies and their application to development and learning are discussed in the current paper. MRDD Research Reviews 2003;9:161,167. © 2003 Wiley-Liss, Inc. [source] Enhancer detection in zebrafish permits the identification of neuronal subtypes that express Hox4 paralogsDEVELOPMENTAL DYNAMICS, Issue 8 2008Beena Punnamoottil Abstract Activity of zebrafish hoxb4a in the developing brain was analyzed in comparison to hoxa4a and hoxd4a using unique enhancer detection transgenes. Cytoplasmic YFP revealed shape and axonal projections of neurons in animals with insertions near the Hox4 genes and provided a means for the identification of neuronal subtypes. Despite an early activity of the genes in neuroepithelial cells and later in immature postmitotic neurons, we found reporter expression in distinct neuronal subtypes in the r7,r8-derived hindbrain. Most strikingly, hoxb4a neuronal subtypes projected through the vagus and into the pectoral fin while others formed symmetrically located fiber tracts innervating the cerebellum and the tectum, features that are partially shared by the other two paralogs. Collectively, our expression analysis indicates that hoxb4a in combination with its paralogs may play a significant role in the development of precerebellar, vagal, and pectoral fin neuronal subtypes. Developmental Dynamics 237:2195,2208, 2008. © 2008 Wiley-Liss, Inc. [source] Rab23 GTPase is expressed asymmetrically in Hensen's node and plays a role in the dorsoventral patterning of the chick neural tubeDEVELOPMENTAL DYNAMICS, Issue 11 2007Naixin Li Abstract The mouse Rab23 protein, a Ras-like GTPase, inhibits signaling through the Sonic hedgehog pathway and thus exerts a role in the dorsoventral patterning of the spinal cord. Rab23 mouse mutant embryos lack dorsal spinal cord cell types. We cloned the chicken Rab23 gene and studied its expression in the developing nervous system. Chick Rab23 mRNA is initially expressed in the entire neural tube but retracts to the dorsal alar plate. Unlike in mouse, we find Rab23 in chick already expressed asymmetrically during gastrulation. Ectopic expression of Rab23 in ventral midbrain induced dorsal genes (Pax3, Pax7) ectopically and reduced ventral genes (Nkx2.2 and Nkx6) without influencing cell proliferation or neurogenesis. Thus, in the developing brain of chick embryos Rab23 acts in the same manner as described for the caudal spinal cord in mouse. These data indicate that Rab23 plays an important role in patterning the dorso-ventral axis by dorsalizing the neural tube. Developmental Dynamics 236:2993,3006, 2007. © 2007 Wiley-Liss, Inc. [source] Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic developmentDEVELOPMENTAL DYNAMICS, Issue 10 2006Elena M. Akhmametyeva Abstract Mutations in the Neurofibromatosis 2 (NF2) gene are associated with predisposition to vestibular schwannomas, spinal schwannomas, meningiomas, and ependymomas. Presently, how NF2 is expressed during embryonic development and in the tissues affected by neurofibromatosis type 2 (NF2) has not been well defined. To examine NF2 expression in vivo, we generated transgenic mice carrying a 2.4-kb NF2 promoter driving ,-galactosidase (,-gal) with a nuclear localization signal. Whole-mount embryo staining revealed that the NF2 promoter directed ,-gal expression as early as embryonic day E5.5. Strong expression was detected at E6.5 in the embryonic ectoderm containing many mitotic cells. ,-gal staining was also found in parts of embryonic endoderm and mesoderm. The ,-gal staining pattern in the embryonic tissues was corroborated by in situ hybridization analysis of endogenous Nf2 RNA expression. Importantly, we observed strong NF2 promoter activity in the developing brain and in sites containing migrating cells including the neural tube closure, branchial arches, dorsal aorta, and paraaortic splanchnopleura. Furthermore, we noted a transient change of NF2 promoter activity during neural crest cell migration. While little ,-gal activity was detected in premigratory neural crest cells at the dorsal ridge region of the neural fold, significant activity was seen in the neural crest cells already migrating away from the dorsal neural tube. In addition, we detected considerable NF2 promoter activity in various NF2-affected tissues such as acoustic ganglion, trigeminal ganglion, spinal ganglia, optic chiasma, the ependymal cell-containing tela choroidea, and the pigmented epithelium of the retina. The NF2 promoter expression pattern during embryogenesis suggests a specific regulation of the NF2 gene during neural crest cell migration and further supports the role of merlin in cell adhesion, motility, and proliferation during development. Developmental Dynamics 235:2771,2785, 2006. © 2006 Wiley-Liss, Inc. [source] Developmental analysis of activin-like kinase receptor-4 (ALK4) expression in Xenopus laevisDEVELOPMENTAL DYNAMICS, Issue 2 2005Yumei Chen Abstract The type I transforming growth factor-beta (TGF,) receptor, activin-like kinase-4 (ALK4), is an important regulator of vertebrate development, with roles in mesoderm induction, primitive streak formation, gastrulation, dorsoanterior patterning, and left,right axis determination. To complement previous ALK4 functional studies, we have analyzed ALK4 expression in embryos of the frog, Xenopus laevis. Results obtained with reverse transcriptase-polymerase chain reaction indicate that ALK4 is present in both the animal and vegetal poles of blastula stage embryos and that expression levels are relatively constant amongst embryos examined at blastula, gastrula, neurula, and early tail bud stages. However, the tissue distribution of ALK4 mRNA, as assessed by whole-mount in situ hybridization, was found to change over this range of developmental stages. In the blastula stage embryo, ALK4 is detected in cells of the animal pole and the marginal zone. During gastrulation, ALK4 is detected in the outer ectoderm, involuting mesoderm, blastocoele roof, dorsal lip, and to a lesser extent, in the endoderm. At the onset of neurulation, ALK4 expression is prominent in the dorsoanterior region of the developing head, the paraxial mesoderm, and midline structures, including the prechordal plate and neural folds. Expression in older neurula stage embryos resolves to the developing brain, somites, notochord, and neural crest; thereafter, additional sites of ALK4 expression in tail bud stage embryos include the spinal cord, otic placode, developing eye, lateral plate mesoderm, branchial arches, and the bilateral heart fields. Together, these results not only reflect the multiple developmental roles that have been proposed for this TGF, receptor but also define spatiotemporal windows in which ALK4 may function to modulate fundamental embryological events. Developmental Dynamics 232:393,398, 2005. © 2004 Wiley-Liss, Inc. [source] A MAGE/NDN-like gene in zebrafishDEVELOPMENTAL DYNAMICS, Issue 3 2003Jocelyn M. Bischof Abstract The human necdin/MAGE gene family has over 50 members, but most of the proteins encoded by these genes are of unknown function. We have now identified a single locus in Danio rerio that encodes a putative protein with significant coding sequence similarity to the mammalian NDN/MAGE genes. Analysis of the complete Fugu ribripes genome sequence also suggests that there is only a single MAGE-like gene in teleost fish. mage is expressed in the larval and adult brain, specifically the retina, the medial region of the telencephalon, periventricular gray zone of the optic tectum, and most highly in the cerebellar corpus. The discovery of a zebrafish NDN/MAGE gene expressed the developing brain facilitates studies of the MAGE homology domain in vertebrate development. Developmental Dynamics, 2003. © 2003 Wiley-Liss, Inc. [source] Stroke in the developing brain and intractable epilepsy: effect of timing on hippocampal sclerosisDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2003Waney Squier FRCP FRC Path A detailed study was made of the pathology of specimens removed by hemispherectomy for the treatment of intractable epilepsy in children with unilateral middle cerebral artery stroke. Neuropathological criteria were used to differentiate strokes that occurred in early intrauterine development (before 28 weeks gestational age) from those occurring in the last trimester, at birth, or after birth: 19 children had early strokes and 21 late. There was no difference in seizure history or occurrence of febrile convulsions in these two groups. Hippocampal tissue was available in 20 patients; pathology in the hippocampus, remote from the infarcted area, showed a marked difference between early-onset and late-onset groups. Hippocampal sclerosis was uncommon in children with early-onset strokes but developed in most of the children whose strokes were of later origin. However, hippocampal sclerosis was more closely related to a clinical history of a late initial precipitating insult irrespective of infarct timing. These findings demonstrate the changing vulnerability of the developing brain and show that hippocampal pathology is more closely related to the timing of an insult than seizure history or the occurrence of febrile convulsions. [source] MR imaging methods for assessing fetal brain developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2008Mary Rutherford Abstract Fetal magnetic resonance imaging provides an ideal tool for investigating growth and development of the brain in vivo. Current imaging methods have been hampered by fetal motion but recent advances in image acquisition can produce high signal to noise, high resolution 3-dimensional datasets suitable for objective quantification by state of the art post acquisition computer programs. Continuing development of imaging techniques will allow a unique insight into the developing brain, more specifically process of cell migration, axonal pathway formation, and cortical maturation. Accurate quantification of these developmental processes in the normal fetus will allow us to identify subtle deviations from normal during the second and third trimester of pregnancy either in the compromised fetus or in infants born prematurely. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] Optical imaging of infants' neurocognitive development: Recent advances and perspectivesDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2008Yasuyo Minagawa-Kawai Abstract Near-infrared spectroscopy (NIRS) provides a unique method of monitoring infant brain function by measuring the changes in the concentrations of oxygenated and deoxygenated hemoglobin. During the past 10 years, NIRS measurement of the developing brain has rapidly expanded. In this article, a brief discussion of the general principles of NIRS, including its technical advantages and limitations, is followed by a detailed review of the role played so far by NIRS in the study of infant perception and cognition, including language, and visual and auditory functions. Results have highlighted, in particular, the developmental changes of cerebral asymmetry associated with speech acquisition. Finally, suggestions for future studies of neurocognitive development using NIRS are presented. Although NIRS studies of the infant brain have yet to fulfill their potential, a review of the work done so far indicates that NIRS is likely to provide many unique insights in the field of developmental neuroscience. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008 [source] A diffusible signal attracts olfactory sensory axons toward their target in the developing brain of the mothDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2003Lynne A. Oland Abstract The signals that olfactory receptor axons use to navigate to their target in the CNS are still not well understood. In the moth Manduca sexta, the primary olfactory pathway develops postembryonically, and the receptor axons navigate from an experimentally accessible sensory epithelium to the brain along a pathway long enough for detailed study of regions in which axon behavior changes. The current experiments ask whether diffusible factors contribute to receptor axon guidance. Explants were made from the antennal receptor epithelium and co-cultured in a collagen gel matrix with slices of various regions of the brain. Receptor axons were attracted toward the central regions of the brain, including the protocerebrum and antennal lobe. Receptor axons growing into a slice of the most proximal region of the antennal nerve, where axon sorting normally occurs, showed no directional preference. When the antennal lobe was included in the slice, the receptor axons entering the sorting region grew directly toward the antennal lobe. Taken together with the previous in vivo experiments, the current results suggest that an attractive diffusible factor can serve as one cue to direct misrouted olfactory receptor axons toward the medial regions of the brain, where local cues guide them to the antennal lobe. They also suggest that under normal circumstances, in which the receptor axons follow a pre-existing pupal nerve to the antennal lobe, the diffusible factor emanating from the lobe acts in parallel and at short range to maintain the fidelity of the path into the antennal lobe. © 2003 Wiley Periodicals, Inc. J Neurobiol 56: 24,40, 2003 [source] Neonatal alcohol exposure impairs acquisition of eyeblink conditioned responses during discrimination learning and reversal in weanling ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2007Kevin L. Brown Abstract Discrimination and reversal of the classically conditioned eyeblink response depends on cerebellar,brainstem interactions with the hippocampus. Neonatal "binge" exposure to alcohol at doses of 5 g/kg/day or more has been shown to impair single-cue eyeblink conditioning in both weanling and adult rats. The present study exposed neonatal rats to acute alcohol intubations across different developmental periods (postnatal day [PND] 4-9 or PND7-9) and tested them from PND26-31 on discriminative classical eyeblink conditioning and reversal. A high dose of alcohol (5 g/kg/day) dramatically impaired conditioning relative to controls when exposure occurred over PND4-9, but produced mild or no impairments when delivered over PND7-9. These findings support previous claims that developmental exposure period plays a critical role in determining the deleterious effects of alcohol on the developing brain. A lower dose of alcohol (4 g/kg/day) delivered from PND4-9,lower than has previously been shown to affect single-cue eyeblink conditioning,also produced deficits on the discrimination task, suggesting that discrimination learning and acquisition of responding to CS+ during reversal may be especially sensitive behavioral indicators of alcohol-induced brain damage in this rat model. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 243,257, 2007. [source] Sensori-motor experience leads to changes in visual processing in the developing brainDEVELOPMENTAL SCIENCE, Issue 2 2010Karin Harman James Since Broca's studies on language processing, cortical functional specialization has been considered to be integral to efficient neural processing. A fundamental question in cognitive neuroscience concerns the type of learning that is required for functional specialization to develop. To address this issue with respect to the development of neural specialization for letters, we used functional magnetic resonance imaging (fMRI) to compare brain activation patterns in pre-school children before and after different letter-learning conditions: a sensori-motor group practised printing letters during the learning phase, while the control group practised visual recognition. Results demonstrated an overall left-hemisphere bias for processing letters in these pre-literate participants, but, more interestingly, showed enhanced blood oxygen-level-dependent activation in the visual association cortex during letter perception only after sensori-motor (printing) learning. It is concluded that sensori-motor experience augments processing in the visual system of pre-school children. The change of activation in these neural circuits provides important evidence that ,learning-by-doing' can lay the foundation for, and potentially strengthen, the neural systems used for visual letter recognition. [source] Auditory verb perception recruits motor systems in the developing brain: an fMRI investigationDEVELOPMENTAL SCIENCE, Issue 6 2009Karin Harman James This study investigated neural activation patterns during verb processing in children, using fMRI (functional Magnetic Resonance Imaging). Preschool children (aged 4,6) passively listened to lists of verbs and adjectives while neural activation was measured. Findings indicated that verbs were processed differently than adjectives, as the verbs recruited motor systems in the frontal cortex during auditory perception, but the adjectives did not. Further evidence suggested that different types of verbs activated different regions in the motor cortex. The results demonstrate that the motor system is recruited during verb perception in the developing brain, reflecting the embodied nature of language learning and processing. [source] Basic principles of MRI and morphometry studies of human brain developmentDEVELOPMENTAL SCIENCE, Issue 3 2002David N. Kennedy Magnetic resonance imaging has undergone dramatic development in the past years. This has been paralleled by developments in the tools for extracting quantitative information from these images in support of capturing the anatomic features of brain development in living humans. This has revolutionized our expectations for current and future diagnostic and investigative work with the developing brain. This paper will cover the classes of information that are readily available in the MR image, the mechanisms for extracting quantitative results, and a sample of the application of these types of methods to developmental issues. These applications highlight tissue- and anatomic-based contrasts in the nature and rate of developmental maturation within the brain. This will be followed by a discussion of the emergent themes of developmental science as elucidated by these classes of observation. [source] The magnocellular theory of developmental dyslexiaDYSLEXIA, Issue 1 2001John Stein Abstract Low literacy is termed ,developmental dyslexia' when reading is significantly behind that expected from the intelligence quotient (IQ) in the presence of other symptoms,incoordination, left,right confusions, poor sequencing,that characterize it as a neurological syndrome. 5,10% of children, particularly boys, are found to be dyslexic. Reading requires the acquisition of good orthographic skills for recognising the visual form of words which allows one to access their meaning directly. It also requires the development of good phonological skills for sounding out unfamiliar words using knowledge of letter sound conversion rules. In the dyslexic brain, temporoparietal language areas on the two sides are symmetrical without the normal left-sided advantage. Also brain ,warts' (ectopias) are found, particularly clustered round the left temporoparietal language areas. The visual magnocellular system is responsible for timing visual events when reading. It therefore signals any visual motion that occurs if unintended movements lead to images moving off the fovea (,retinal slip'). These signals are then used to bring the eyes back on target. Thus, sensitivity to visual motion seems to help determine how well orthographic skill can develop in both good and bad readers. In dyslexics, the development of the visual magnocellular system is impaired: development of the magnocellular layers of the dyslexic lateral geniculate nucleus (LGN) is abnormal; their motion sensitivity is reduced; many dyslexics show unsteady binocular fixation; hence poor visual localization, particularly on the left side (left neglect). Dyslexics' binocular instability and visual perceptual instability, therefore, can cause the letters they are trying to read to appear to move around and cross over each other. Hence, blanking one eye (monocular occlusion) can improve reading. Thus, good magnocellular function is essential for high motion sensitivity and stable binocular fixation, hence proper development of orthographic skills. Many dyslexics also have auditory/phonological problems. Distinguishing letter sounds depends on picking up the changes in sound frequency and amplitude that characterize them. Thus, high frequency (FM) and amplitude modulation (AM) sensitivity helps the development of good phonological skill, and low sensitivity impedes the acquisition of these skills. Thus dyslexics' sensitivity to FM and AM is significantly lower than that of good readers and this explains their problems with phonology. The cerebellum is the head ganglion of magnocellular systems; it contributes to binocular fixation and to inner speech for sounding out words, and it is clearly defective in dyslexics. Thus, there is evidence that most reading problems have a fundamental sensorimotor cause. But why do magnocellular systems fail to develop properly? There is a clear genetic basis for impaired development of magnocells throughout the brain. The best understood linkage is to the region of the Major Histocompatibility Complex (MHC) Class 1 on the short arm of chromosome 6 which helps to control the production of antibodies. The development of magnocells may be impaired by autoantibodies affecting the developing brain. Magnocells also need high amounts of polyunsaturated fatty acids to preserve the membrane flexibility that permits the rapid conformational changes of channel proteins which underlie their transient sensitivity. But the genes that underlie magnocellular weakness would not be so common unless there were compensating advantages to dyslexia. In developmental dyslexics there may be heightened development of parvocellular systems that underlie their holistic, artistic, ,seeing the whole picture' and entrepreneurial talents. Copyright © 2001 John Wiley & Sons, Ltd. [source] Pentylenetetrazol-induced Recurrent Seizures in Rat Pups: Time Course on Spatial Learning and Long-term EffectsEPILEPSIA, Issue 6 2002Li-Tung Huang Summary: ,Purpose: Recurrent seizures in infants are associated with a high incidence of neurocognitive deficits. Animal models have suggested that the immature brain is less vulnerable to seizure-induced injury than is that in adult animals. We studied the effects of recurrent neonatal seizures on cognitive tasks performed when the animals were in adolescence and adulthood. Methods: Seizures were induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for spatial memory by using the Morris water maze task. In adulthood, motor performance was examined by the Rotarod test, and activity level was assessed by the open field test. Seizure threshold was examined by inhalant flurothyl. To assess presence or absence of spontaneous seizures, rats were video recorded for 4 h/day for 10 consecutive days for the detection of spontaneous seizures. Finally, brains were examined for histologic evidence of injury with cresyl violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell layers of the hippocampus. Results: PTZ-treated rats showed significant spatial deficits in the Morris water maze at both P35 and P60. There were no differences in seizure threshold, motor balance, or activity level during the open field test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain showed no cell loss in either the control or experimental rats. PTZ-treated rats exhibited more Timm staining in the CA3 subfield. However, the control and experimental rats showed similar Timm staining within the supragranular zone. Conclusions: Our findings indicate that recurrent PTZ-induced seizures result in long-term cognitive deficits and morphologic changes in the developing brain. Furthermore, these cognitive deficits could be detected during pubescence. [source] Impaired nerve regeneration in reeler mice after peripheral nerve injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Erika Lorenzetto Abstract Reelin, an extracellular matrix protein, plays an important role in the regulation of neuronal migration and cortical lamination in the developing brain. Little is known, however, about the role of this protein in axonal regeneration. We have previously shown that Reelin is secreted by Schwann cells in the peripheral nerve compartment during postnatal development and that it is up-regulated following nerve injury in adult mice. In this work, we generated mice deficient in Reelin (reeler) that express yellow fluorescent protein (YFP) in a subset of neurons and examined the axonal regeneration following nerve crush. We found that axonal regeneration was significantly altered compared with wild-type mice. By contrast, retrograde tracing with Fluorogold dye after sciatic nerve crush was unaffected in these mutants, being comparable with normal axonal transport observed in wild-type. These results indicate that the absence of Reelin impairs axonal regeneration following injury and support a role for this protein in the process of peripheral nerve regeneration. [source] Hypoxia induces complex I inhibition and ultrastructural damage by increasing mitochondrial nitric oxide in developing CNSEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Sebastián Giusti Abstract NO-mediated toxicity contributes to neuronal damage after hypoxia; however, the molecular mechanisms involved are still a matter of controversy. Since mitochondria play a key role in signalling neuronal death, we aimed to determine the role of nitrative stress in hypoxia-induced mitochondrial damage. Therefore, we analysed the biochemical and ultrastructural impairment of these organelles in the optic lobe of chick embryos after in vivo hypoxia,reoxygenation. Also, we studied the NO-dependence of damage and examined modulation of mitochondrial nitric oxide synthase (mtNOS) after the hypoxic event. A transient but substantial increase in mtNOS content and activity was observed at 0,2 h posthypoxia, resulting in accumulation of nitrated mitochondrial proteins measured by immunoblotting. However, no variations in nNOS content were observed in the homogenates, suggesting an increased translocation to mitochondria and not a general de novo synthesis. In parallel with mtNOS kinetics, mitochondria exhibited prolonged inhibition of maximal complex I activity and ultrastructural phenotypes associated with swelling, namely, fading of cristae, intracristal dilations and membrane disruption. Administration of the selective nNOS inhibitor 7-nitroindazole 20 min before hypoxia prevented complex I inhibition and most ultrastructural damage. In conclusion, we show here for the first time that hypoxia induces NO-dependent complex I inhibition and ultrastructural damage by increasing mitochondrial NO in the developing brain. [source] Inactivation of the gene for the nuclear receptor tailless in the brain preserving its function in the eyeEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2007Thorsten Belz Abstract During embryogenesis, tailless, an orphan member of the nuclear receptor family, is expressed in the germinal zones of the brain and the developing retina, and is involved in regulating the cell cycle of progenitor cells. Consequently, a deletion of the tailless gene leads to decreased cell number with associated anatomical defects in the limbic system, the cortex and the eye. These structural abnormalities are associated with blindness, increased aggressiveness, poor performance in learning paradigms and reduced anxiousness. In order to assess the contribution of blindness to the behavioural changes, we established tailless mutant mice with intact visual abilities. We generated a mouse line in which the second exon of the tailless gene is flanked by loxP sites and crossed these animals with a transgenic line expressing the Cre recombinase in the neurogenic area of the developing brain, but not in the eye. The resulting animals have anatomically indistinguishable brains compared with tailless germline mutants, but are not blind. They are less anxious and much more aggressive than controls, like tailless germline mutants. In contrast to germline mutants, the conditional mutants are not impaired in fear conditioning. Furthermore, they show good performance in the Morris water-maze despite severely reduced hippocampal structures. Thus, the pathological aggressiveness and reduced anxiety found in tailless germline mutants are due to malformations caused by inactivation of the tailless gene in the brain, but the poor performance of tailless null mice in learning and memory paradigms is dependent on the associated blindness. [source] Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2003Annalisa Bolis Abstract Rac3 is one of the three known Rac GTPases in vertebrates. Rac3 shows high sequence homology to Rac1, and its transcript is specifically expressed in the developing nervous system, where its localization and function are unknown. By using Rac3-specific antibodies, we show that the endogenous Rac3 protein is differentially expressed during mouse brain development, with a peak of expression at times of neuronal maturation and synaptogenesis. Comparison with Rac1 shows clear-cut differences in the overall distribution of the two GTPases in the developing brain, and in their subcellular distribution in regions of the brain where both proteins are expressed. At P7, Rac3 staining is particularly marked in the deep cerebellar nuclei and in the pons, where it shows a discontinuous distribution around the neuronal cell bodies, in contrast with the diffuse staining of Rac1. Rac3 does not evidently co-localize with pre- and post-synaptic markers, nor with GFAP-positive astrocytes, but it clearly co-localizes with actin filaments, and with the terminal portions of calbindin-positive Purkinje cell axons in the deep cerebellar nuclei. Our data implicate Rac3 in neuronal differentiation, and support a specific role of this GTPase in actin-mediated remodelling of Purkinje cell neuritic terminals at time of synaptogenesis. [source] Characterization of teleost Mdga1 using a gene-trap approach in medaka (Oryzias latipes)GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 8 2009Shinya Sano Abstract MAM domain containing glycosilphosphatidilinositol anchor 1 (MDGA1) is an IgCAM protein present in many vertebrate species including humans. In mammals, MDGA1 is expressed by a subset of neurons in the developing brain and thought to function in neural cell migration. We identified a fish ortholog of mdga1 by a gene-trap screen utilizing the Frog Prince transposon in medaka (Japanese killifish, Oryzias latipes). The gene-trap vector was inserted into an intronic region of mdga1 to form a chimeric protein with green fluorescent protein, allowing us to monitor mdga1 expression in vivo. Expression of medaka mdga1 was seen in various types of embryonic brain neurons, and specifically in neurons migrating toward their target sites, supporting the proposed function of MDGA1. We also isolated the closely related mdga2 gene, whose expression partially overlapped with that of mdga1. Despite the fact that the gene-trap event eliminated most of the functional domains of the Mdga1 protein, homozygous embryos developed normally without any morphological abnormality, suggesting a functional redundancy of Mdga1 with other related proteins. High sequential homology of MDGA proteins between medaka and other vertebrate species suggests an essential role of the MDGA gene family in brain development among the vertebrate phylum. genesis 47:505,513, 2009. © 2009 Wiley-Liss, Inc. [source] Human CYP11A1 promoter drives Cre recombinase expression in the brain in addition to adrenals and gonadsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2007Hsu-Shui Wu Abstract The first step of steroid biosynthesis is catalyzed by cytochrome P450scc, encoded by CYP11A1. To achieve steroidogenic tissue-specific inactivation of genes in vivo by the Cre-loxP approach, we used the 4.4-kb regulatory region of the human CYP11A1 gene to drive Cre recombinase expression in the tissues that produce steroids. The resulting SCC-Cre mice express high levels of Cre in the adrenal cortex and gonads at the same sites as that for the endogenous CYP11A1 expression. In addition, Cre activity was found in the diencephalon and midbrain. In the developing brain, the Cre activity was first detected in the embryonic day 10.5. Our study is the first to show that the 4.4-kb CYP11A1 promoter is transcriptionally active in the brain in vivo. genesis 45:59,65, 2007. © 2007 Wiley-Liss, Inc. [source] Rat choroid plexuses contain myeloid progenitors capable of differentiation toward macrophage or dendritic cell phenotypesGLIA, Issue 3 2006Serge Nataf Abstract The interface between the blood and the cerebrospinal fluid (CSF) is formed by the choroid plexuses (CPs), which are specialized structures located within the brain ventricles. They are composed of a vascularized stroma surrounded by a tight epithelium that controls molecular and cellular traffic between the blood and the CSF. Cells expressing myeloid markers are present within the choroidal stroma. However, the exact identity, maturation state, and functions of these CP-associated myeloid cells are not fully clarified. We show here that this cell population contains immature myeloid progenitors displaying a high proliferative potential. Thus, in neonate rats and, to a lesser extent, in adult rats, cultured CP stroma cells form large colonies of macrophages, in response to M-CSF or GM-CSF, while, under the same conditions, peripheral blood monocytes do not. In addition, under GM-CSF treatment, free-floating colonies of CD11c+ monocytic cells are generated which, when restimulated with GM-CSF and IL-4, differentiate into OX62+/MHC class II+ dendritic cells. Interestingly, in CP stroma cultures, myeloid cells are found in close association with fibroblastic-like cells expressing the neural stem-cell marker nestin. Similarly, in the developing brain, macrophages and nestin+ fibroblastic cells accumulate in vivo within the choroidal stroma. Taken together, these results suggest that the CP stroma represents a niche for myeloid progenitors and may serve as a reservoir for brain macrophages. © 2006 Wiley-Liss, Inc. [source] Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: Beneficial effect of dextromethorphanHIPPOCAMPUS, Issue 6 2006San Nan Yang Abstract Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREBSerine-133), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28,29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREBSerine-133, and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy. © 2006 Wiley-Liss, Inc. [source] Neuroimaging of the developing brain: Taking "developing" seriouslyHUMAN BRAIN MAPPING, Issue 6 2010Annette Karmiloff-Smith Abstract With a few notable exceptions, many studies, be they behavioral, neuroimaging, or genetic, are snapshots that compare one child group to one adult group, which capture only two points in time and tell the scientist nothing about the mechanisms underlying neural trajectories over developmental time. Thus, a distinction needs to be drawn between child neuroimaging and developmental neuroimaging, the latter approach being relevant not just to children, but to adults and the ageing brain. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc. [source] Brain and behavior interface: Stress and the developing brainINFANT MENTAL HEALTH JOURNAL, Issue 3 2003Megan R. Gunnar Animal studies have shown that mother,infant interactions can have long-term impacts on areas of the brain that regulate fearful behavior and the physiology of stress. Here, the research on human infants and children is reviewed with an eye to whether early experiences have similar effects in our species. Research shows that during the first year, sensitive and responsive caregiving becomes a powerful regulator of emotional behavior and neuroendocrine stress hormone activity in young children. Indeed, quality-of-care effects can be detected for children throughout the preschool years. Reviewed research suggests that temperament affects the likelihood that children will show increases in stress hormones as the quality of their care decreases. Finally, we review the literature on stress hormone activity in children who have been maltreated early in life, and explore the critical question of whether enhancing care later in development can reverse the effects on behavior and neurobiology of early adverse experiences. ©2003 Michigan Association for Infant Mental Health. [source] | |||||||||||||||||||||||||||||||