Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “cortical development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed2006

Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA1-G(i/o) pathway.

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates cortical development. Here we examined how LPA influences the cell fate of cortical neuroblasts using a neurosphere culture system. We generated neurospheres in the presence of basic fibroblast growth factor (bFGF). Treatment with LPA throughout the culture period significantly reduced the number of cells in the neurospheres. When dissociated single cells derived from neurospheres were induced to differentiate by adherence on coverslips, the proportion of MAP2-positive neurons was higher in LPA-treated neurospheres than in those treated with bFGF alone, and the proportion of myelin basic protein-positive oligodendrocytes was lower. Consistent with this finding, LPA raised the ratio of beta-tubulin type III-positive young neurons and reduced the ratio of CD140a-positive oligodendrocyte precursors in neurospheres. These effects of LPA were inhibited by pretreatment of neurospheres with pertussis toxin or an LPA(1)-preferring antagonist, Ki16425. Moreover, LPA-induced enhancement of neuronal differentiation was not observed in neurospheres derived from lpa(1)-null mice. These results suggest that LPA promotes the commitment of neuroblasts to the neural lineage through the LPA(1)-G(i/o) pathway.

Animals↗
PubMed2006

Functional degradation of visual cortical cells in old cats.

Visual function declines with age. Using extracellular single-unit in vivo recordings, we compared the function of primary visual cortical (area 17) cells in young and old paralyzed, anesthetized cats. The results reveal that cortical neurons in old cats exhibit higher visually evoked responses, higher spontaneous activities, lower signal-to-noise ratios, and weaker orientation and direction selectivity than do cells in young adult cats. These findings are consistent with previously reported age related declines in cortical function in senescent macaque monkeys. Thus, similar declines in cortical function accompany old age in different mammalian species with well developed cortices.

Action Potentials↗
PubMed1999

The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia.

BACKGROUND: Pathology of dorsolateral prefrontal cortex and dysregulation of dopaminergic neurons have been associated with the pathophysiology of schizophrenia, but how these phenomena relate to each other in patients has not been known. It has been hypothesized that prefrontal cortical pathology might induce both diminished steady-state and exaggerated responses of dopaminergic neurons to certain stimuli (e.g., stress). We examined the relationship between a measure of prefrontal neuronal pathology and striatal dopamine activity in patients with schizophrenia and in a nonhuman primate model of abnormal prefrontal cortical development. METHODS: In the patients, we studied in vivo markers of cortical neuronal pathology with NMR spectroscopic imaging and of steady-state striatal dopamine activity with radioreceptor imaging. In the monkeys, we used the same NMR technique and in vivo microdialysis. RESULTS: Measures of N-acetyl-aspartate concentrations (NAA) in dorsolateral prefrontal cortex strongly and selectively predicted D2 receptor availability in the striatum (n = 14, rho = -.64, p < .01), suggesting that the greater the apparent dorsolateral prefrontal cortex pathology, the less the steady-state dopamine activity in these patients. A similar relationship between NAA measures in dorsolateral prefrontal cortex and steady-state dopamine concentrations in the striatum was found in the monkeys (n = 5, rho = .70, p < .05). We then tested in the same monkeys the relationship of prefrontal NAA and striatal dopamine overflow following amphetamine infusion into dorsolateral prefrontal cortex. Under these conditions, the relationship was inverted, i.e., the greater the apparent dorsolateral prefrontal cortex pathology, the greater the dopamine release. CONCLUSIONS: These data demonstrate direct relationships between putative neuronal pathology in dorsolateral prefrontal cortex and striatal dopamine activity in human and nonhuman primates and implicate a mechanism for dopamine dysregulation in schizophrenia.

Adult↗
PubMedDate not supplied

Burst suppression and impairment of neocortical ontogenesis: electroclinical and neuropathologic findings in two infants with early myoclonic encephalopathy.

We report the electroclinical and neuropathologic correlations in 2 children aged 2.5 months affected by early myoclonic encephalopathy characterized by epileptic seizures, erratic myoclonus, and an EEG pattern of burst suppression. Despite different etiologies, the neuropathologic findings showed similar abnormalities in both cases, with no substantial impairment of the myelination processes. Islands of matrix tissue scattered in the periventricular region and neurons aligned marginally in the bulbar olives were detected. The presence of numerous large spiny neurons dispersed in the white matter along the axons of the cortical gyri was the most striking finding. The neurons have been interpreted as abnormally persisting interstitial cells in 2.5-month-old children. These early generated neurons, normally present during neocortical histogenesis, are programmed to die near the end of gestation or soon after birth. The interstitial cells are regarded as a waiting compartment of afferent fibers during cortical development. Their persistence in our patients represents an anatomic condition for cortical disconnection providing a pathophysiologic basis to burst-suppression phenomena.

Brain↗
PubMed2005

Severe periprosthetic cortical atrophy in the skeletally immature: a report of three cases.

We describe three patients who developed cortical bone atrophy around cemented endoprostheses used for partial femur reconstructions after resection of Ewing's sarcoma. We believe this to be related to remodeling secondary to stress-shielding. Rather than increased porosity and decreased mineral density, the stress-shielding in these skeletally immature patients resulted in altered morphology of the cortical bone, with apparent maintenance of density.

Atrophy↗
PubMed2003

Developmental and evolutionary adaptations of cortical radial glia.

The concept of transient radial glial cells, based originally on observations made on the human fetal brain stained with the classical Golgi silver impregnation method, has been evolving with the application of advanced methods of anatomy, molecular biology and genetics. In addition to providing scaffolding for migration and placement of neurons, these specialized cells can generate neuronal cell lineage that either immediately, or following multiple divisions, migrate along the elongated radial process of the mother cell. Comparative analysis of the data on emergence, function and morphogenetic transformation of radial glial cells in the mouse, macaque and human embryonic cerebral wall reveals both similarities as well as species-specific differences in the timing, sequence, biochemical composition and level of phenotypic differentiation that provide insight into cortical development and evolution, as well as into pathogenesis of genetic and acquired cortical abnormalities.

Adaptation, Physiological↗
PubMed1980

Effects of auditory cortical lesions on sound localization by the rat.

1. Studies with cats, dogs, and monkeys have shown that bilateral ablation of auditory cortex can result in severe deficits in the ability to localize sounds in space. In the present series of studies we sought to extend this observation to include the laboratory rat. 2. Rats were tested in a two-choice sound-localization task, which required a spatial response to a distant goal box. Although the test conditions were very similar to those employed with cat, dog, and monkey, deficits following cortical ablation were minimal. Indeed, following bilateral ablation of both primary and secondary auditory projection areas, rats were still capable of localization at small angles. 3. Several possibilities were considered to explain the apparent species difference in the effect of cortical ablations. It seemed unlikely that the difference was due simply to testing procedures or details of stimulus presentation. Central nervous system factors were discussed, including the possibility that the degree of impairment was related to the extent of cortical development in different species. It was concluded that the effects of auditory cortical ablation are not the same for all mammals and that for some species auditory cortex is not essential for sound localization.

Animals↗
PubMed2004

[Refractory partial epilepsy: morphological imaging in children].

The imaging approach to refractory partial epilepsy in children is essentially the same as the one used for any epilepsy at that age, except that surgery being generally proposed, it has to be oriented and complete. Yet there are differences. Sedation introduces a risk. The brain of the young child is still immature, and specially designed sequences are needed for proper imaging. Brain immaturity also modifies the usual image contrast and may conceal (or on the contrary enhance) an area of dysplasia. Repeating studies after a few months has to be considered. Obviously, the brain imaging study has to be closely oriented by the clinical and EEG findings and if necessary, by functional imaging data. The abnormalities are extremely diverse as compared to what is observed in an adult population. The brain may be "normal", or demonstrate only non-specific abnormalities. Among the specific lesions, scars are common, and above all, malformations, especially malformations of cortical development (even diffuse malformations are commonly expressed by partial seizures), including focal cortical dysplasias and their close relatives, dysplastic tumors. In children, the most common lesions in the temporal lobe are scars, tumors/dysplastic lesions and malformative lesions, while mesial sclerosis is significantly less common than in adults. In the event of a simple lesion, the decision for surgery on the basis of morphological data alone is more easily made in children than in adults.

Adolescent↗
PubMed2005

Can we predict refractory epilepsy at the time of diagnosis?

The early prediction of intractability is a major challenge in epileptology. Some prognostic factors have been pointed out, most of which simply underlined that partial epilepsy is more difficult to control than idiopathic generalized epilepsy (IGE). Indeed, the main predictors are the presence of a brain lesion demonstrated by neuroimaging or suggested by a neurological deficit or a developmental delay, as well as electroclinical evidence of non idiopathic partial epilepsy. Little is known about the relationship between the location of the epileptogenic area and the chance of being seizure-free in patients with partial epilepsy. Some data suggest that temporal lobe epilepsy (TLE) is more difficult to control than other partial epilepsies, but this might only reflect the prognostic impact of hippocampal sclerosis. Indeed, several studies have shown that the majority of patients with MRI evidence of hippocampal sclerosis develop refractory epilepsy. This observation also applies to patients with malformation of cortical development (MCD). The response to the first AED is another early predictor of refractory epilepsy. At the time of diagnosis, several prognostic factors are available to predict drug resistance, but further studies are still needed to better delineate the specific role of each of these factors, and to offer a more accurate prediction of long term seizure outcome.

Drug Resistance↗
PubMed2001

Differential cellular expression of neurotrophins in cortical tubers of the tuberous sclerosis complex.

Neurotrophins and their receptors modulate cerebral cortical development. Tubers in the tuberous sclerosis complex (TSC) are characterized histologically by disorganized cortical cytoarchitecture and thus, we hypothesized that expression of neurotrophin mRNAs and proteins might be altered in tubers. Using in situ transcription and mRNA amplification to probe cDNA arrays, we found that neurotrophin-3 (NT3) and trkB mRNA expression were reduced whereas neurotrophin-4 (NT4) and trkC mRNA expression were increased in whole tuber sections. Alterations in mRNA abundance were defined in single microdissected dysplastic neurons (DNs) and giant cells (GCs). NT3 mRNA expression was reduced in GCs and trkB mRNA expression was reduced in DNs. NT4 mRNA expression was increased in DNs and trkC mRNA expression was increased in both DNs and GCs. In three patients, TSC2 locus mutations were confirmed and the mean tuberin mRNA expression levels was reduced across all nine cases. Consistent with these observations, NT3 mRNA expression was reduced but trkC mRNA expression was increased in vitro in human NTera2 neurons (NT2N) transfected with a tuberin antisense construct that reduced tuberin expression. Western analysis of tuber homogenates and computer-assisted densitometry of immunolabeled sections confirmed the neurotrophin mRNA expression data in whole sections and single neurotrophin immunoreactive cells. We conclude that alterations in NT4/trkB and NT3/trkC expression may contribute to tuber formation during brain development as downstream effects of the hamartin and tuberin pathway in TSC.

Adolescent↗
PubMed2004

Oxidative damage and defective DNA repair is linked to apoptosis of migrating neurons and progenitors during cerebral cortex development in Ku70-deficient mice.

DNA repair plays a critical, but imprecisely defined role in neuronal survival during cortical neurogenesis. We examined cortical development in mice deficient for the DNA end-joining protein, Ku70. At gestational day 14.5, corresponding to the peak of neurogenesis, the Ku70(-/-) embryonic cerebral cortex displayed 25- to 30-fold more cell death than heterozygous littermates, as judged by DNA breaks, pyknosis and active caspase-3. In Ku70(-/-) embryos only, large clusters of dying neurons were found in the intermediate zone. Cell death declined until P4, when the number of dying cells became comparable to that in heterozygous mice. Two groups of dying cells were evident: a GLAST(+) neural progenitor population in the subventricular and ventricular zones, and a doublecortin(+) immature neuron population in the intermediate zone, the latter exhibiting strong staining for oxidative DNA damage. Antioxidants and lower oxygen tension reduced the high levels of neuronal death in primary cortical cultures derived from Ku70(-/-) mice, but not the low levels of cell death in wildtype cortical cultures. Results indicate migrating cortical neurons undergo oxidative DNA damage, which is normally repaired by non-homologous end joining. Failure to repair oxidative damage triggers a form of apoptosis involving caspase-3 activation.

Animals↗
PubMed2005

The cerebral cortex malformation in thanatophoric dysplasia: neuropathology and pathogenesis.

Thanatophoric dysplasia (TD) is a relatively common, fatal form of chondrodysplastic dwarfism in which the cerebral cortex displays a unique and complex malformation. The malformation is characterized by a combination of abnormalities, which affect the temporal lobe most severely. Salient features include temporal lobe enlargement, deep transverse sulci across the inferomedial temporal surface, and hippocampal dysplasia. TD is caused by mutations of the fibroblast growth factor (FGF) receptor 3 gene (FGFR3), which result in constitutive activation of the FGFR3 tyrosine kinase. However, the link between constitutive FGFR3 activation and malformation of the cortex has been difficult to elucidate. In this review, I describe the neuropathological features of human TD, especially the cortical malformation, ascertained by examination of 45 published cases and 5 new cases, spanning gestational ages from 18 to 42 weeks. The cortical malformation is interpreted with regard to developmental mechanisms, and observations from a mouse model of TD. The evidence suggests that FGFR3 activation perturbs three key processes in cortical development: areal patterning, progenitor proliferation, and apoptosis. Defective patterning accounts for hippocampal dysplasia, while increased proliferation and decreased apoptosis account for temporal lobe hyperplasia and premature development of aberrant sulci. Disturbances in these processes may also contribute to other cortical malformations.

Animals↗
PubMed2003

Decrease in expression of alpha 5 beta 1 integrin during neuronal differentiation of cortical progenitor cells.

Neuronal differentiation of embryonic neural progenitor cells is regulated by both intrinsic and extrinsic signals. Since dynamic changes in cell shape typify neuronal differentiation, cell adhesion molecules could be relevant to this process. Although it has been reported that fibronectin-integrin interactions are important for the proliferation of neural progenitor cells, little is known about the contribution of integrins to neuronal differentiation. In order to address this shortfall, we examined integrin expression on cortical progenitor cells by using immunohistochemistry and FACS analysis of cells in which GFP expression was driven by regulatory (promoter) regions of the nestin gene (nestin-GFP(+)). We here report that high levels of nestin promoter activity correlated with high expression levels of alpha(5)beta(1) integrin (alpha(5)beta(1)(high) cells). FACS analysis of nestin-GFP(+) cortical cells revealed an additional subpopulation with reduced expression of alpha(5)beta(1) integrin (alpha(5)beta(1)(low) cells). The size of the alpha(5)beta(1)(low) subpopulation increased during cortical development. To investigate the correlation between integrin and neuronal differentiation, nestin-GFP(+) cortical progenitor cells were sorted into alpha(5)beta(1)(high) or alpha(5)beta(1)(low) populations, and each potential to differentiate was analyzed. We show that the nestin-GFP(+) alpha(5)beta(1)(high) population corresponded to broadly multipotential neural progenitor cells, whereas nestin-GFP(+) alpha(5)beta(1)(low) cells appeared to be committed to a neuronal fate. These findings suggest that alpha(5)beta(1) expression on cortical progenitor cells is developmentally regulated and its downregulation is involved in the process of neuronal differentiation.

Animals↗
PubMed1997

Serotonin facilitates synaptic plasticity in kitten visual cortex: an in vitro study.

We have addressed the role of serotonin-2C (5-HT2C) receptors in the development and maintenance of synaptic plasticity in the kitten visual cortex. In visual cortical slices, taken from 40- to 80-day-old kittens, bath application of serotonin markedly facilitated the induction of both long-term depression (LTD) and long-term potentiation (LTP). Field potential responses to white matter stimulation were recorded from layer IV after a regime of low frequency stimulation (LFS; 1 Hz, 15 min), which reliably induced LTP or LTD in younger kittens (less than 30 days of age). At 40-80 days, this protocol almost never induced LTD or LTP in layer IV. However, in 50% of the visual cortical slices studied in 40-80-day-old kittens, LTD or LTP was induced, if serotonin (1 or 10 microM) was co-applied with LFS. No such serotonin facilitation of long-term plasticity was ever detected in > 120-day-old animals, indicating that serotonin facilitates synaptic plasticity within a defined period of visual cortical development. Serotonergic 5-HT2C receptors are likely to contribute to the synaptic plasticity observed in layer IV, since mesulergine, an antagonist of the 5-HT2C receptor, completely blocked synaptic modifications induced by the combination of low frequency stimulation and serotonin application.

Aging↗
PubMed2003

Binocular deficits associated with early alternating monocular defocus. II. Neurophysiological observations.

Experiencing binocularly conflicting signals early in life dramatically alters the binocular responses of cortical neurons. Because visual cortex is highly plastic during a critical period of development, cortical deficits resulting from early abnormal visual experience often mirror the nature of interocular decorrelation of neural signals from the two eyes. In the preceding paper, we demonstrated that monkeys that experienced early alternating monocular defocus (-1.5, -3.0, or -6.0 D) show deficits in stereopsis that generally reflected the magnitude of imposed monocular defocus. Because these results indicated that alternating monocular defocus affected the higher spatial frequency components of visual scenes more severely, we employed microelectrode recording methods to investigate whether V1 neurons in these lens-reared monkeys exhibited spatial-frequency-dependent alterations in their binocular response properties. We found that a neuron's sensitivity to interocular spatial phase disparity was reduced in the treated monkeys and that this reduction was generally more severe for units tuned to higher spatial frequencies. In the majority of the affected units, the disparity-sensitivity loss was associated with interocular differences in monocular receptive field properties. The present results suggest that the behavioral deficits in stereopsis produced by abnormal visual experience reflect at least in part the constraints imposed by alterations at the earliest stages of binocular cortical processing and support the hypothesis that the local disparity processing mechanisms in primates are spatially tuned and can be independently compromised by early abnormal visual experience.

Amblyopia↗
PubMed1992

Formation and preservation of cortical layers in slice cultures.

During cortical development, neurons generated at the same time in the ventricular zone migrate out into the cortical plate and form a cortical layer (Berry and Eayrs, 1963, Nature 197:984-985; Berry and Rogers, 1965, J. Anat. 99:691-709). We have been studying both the formation and maintenance of cortical layers in slice cultures from rat cortex. The bromodeoxyuridine (BrdU) method was used to label cortical neurons on their birthday in vivo. When slice cultures were prepared from animals at different embryonic and postnatal ages, all cortical layers that have already been established in vivo remained preserved for several weeks in vitro. In slice cultures prepared during migration in the cortex, cells continued to migrate towards the pial side of the cortical slice, however, migration ceased after about 1 week in culture. Thus, cortical cells reached their final laminar position only in slice cultures from postnatal animals, whereas in embryonic slice, migrating cells became scattered throughout the cortex. Previous studies demonstrated that radial glia fibers are the major substrate for migrating neurons (Rakic, 1972, J. Comp. Neurol. 145:61-84; Hatten and Mason, 1990, Experientia 46:907-916). Using antibodies directed against the intermediate filament Vimentin, radial glial cells were detected in all slice cultures where cell migration did occur. Comparable to the glia development in vivo, radial glial fibers disappeared and astrocytes containing the glia fibrillary-associated protein (GFAP) differentiated in slice cultures from postnatal cortex, after the neurons have completed their migration. In contrast, radial glial cells were detected over the whole culture period, and very few astrocytes differentiated in embryonic slices, where cortical neurons failed to finish their migration. The results of this study indicate that the local environment is sufficient to sustain the layered organization of the cortex and support the migration of cortical neurons. In addition, our results reveal a close relationship between cell migration and the developmental status of glial cells.

Aging↗
PubMed1992

Properties of amino acid neurotransmitter receptors of embryonic cortical neurons when activated by exogenous and endogenous agonists.

1. The properties of receptors for amino acid neurotransmitters expressed by developing cortical neurons were studied with the use of whole-cell recording in the intact cerebral cortex of embryonic turtles in vitro. The inhibitory agonist gamma-aminobutyric acid (GABA) and the excitatory agonist glutamate were focally applied to single cells under voltage clamp, and the ionic dependence, voltage dependence, and pharmacological sensitivity of the responses were characterized. The responses mediated by a glutamate receptor subtype, the N-methyl-D-aspartate (NMDA) receptor, produced by glutamate and by evoked release of an endogenous excitatory agonist, were compared further. Fluctuation analysis was used to characterize the properties of the NMDA channels and the mechanism of action of receptor antagonists. 2. When postmitotic neurons first appeared at stage 15, all neurons tested responded to GABA with a current that reversed at the equilibrium potential for chloride ions and that was sensitive to the GABAA receptor antagonist bicuculline methiodide (BMI). As development proceeded, an increasing proportion of neurons also responded with a BMI-insensitive current that reversed near the equilibrium potential for potassium ions. This current was blocked by the GABAB receptor antagonist 3-amino-2-propyl phosponic acid (phaclofen). The GABAB agonist baclofen, however, failed to produce a detectable postsynaptic current. 3. Neurons at stage 15 showed a biphasic response to glutamate that reversed at the equilibrium potential for cations. All neurons tested showed a slow, sustained response associated with an increase in current variance compared with background, and, as development proceeded, an increasing proportion also exhibited a fast, transient response. Both fast and slow responses varied linearly with voltage in the absence of Mg2+ ions, but the addition of Mg2+ ions to the bathing medium attenuated the slow response at hyperpolarized potentials. As a result, the current-voltage relation of the slow response in the presence of Mg2+ ions exhibited a region of negative slope conductance, like that of currents mediated by NMDA receptors. 4. The fast and slow responses to glutamate differed in their pharmacological sensitivity. The fast responses were sensitive to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas the slow responses were sensitive to the NMDA receptor antagonist D(-)-2-amino-5-phosphonovalerate (D-APV). 5. When cells were held at -70 mV, glutamate evoked a fluctuating current consisting of channel currents with a mean open time, tau, of 4.42 +/- 0.47 (SE) ms in early postmitotic neurons at stage 15 and 4.99 +/- 0.38 ms at stages 17-20.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1999

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB.

The developing cerebral cortex undergoes a period of substantial cell death. The present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in cerebral cortical development. Fas mRNA and protein are transiently expressed in subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE-inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD, RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-kappaB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL-expressing) cells and that Fas may have functions in addition to suicide in the developing brain.

Adaptor Proteins, Signal Transducing↗