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PubMed2004

Serotonin in autism and pediatric epilepsies.

Serotonergic abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development--and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This review explores the hypothesis that an early disturbance in the serotonin system affects cortical development and the development of thalamocortical innervation, and is a potential mechanism, common to autism and pediatric epilepsies associated with cortical dysplasia. An argument is made that cortical malformation leads to abnormalities of thalamocortical connectivity, and that serotonin plays a critical role in this process. Finally, a role for altered metabolism of the serotonin precursur, tryptophan, in both epilepsy and autism is discussed.

Animals↗
PubMed2002

Rapid development of cortical auditory evoked potentials after early cochlear implantation.

The aim of our research was to estimate the time course of development and plasticity of the human central auditory pathways following cochlear implantation. We recorded cortical auditory-evoked potentials in 3-year-old congenitally deaf children after they were fitted with cochlear implants. Immediately after implantation cortical response latencies resembled those of normal-hearing newborns. Over the next few months, the cortical evoked responses showed rapid changes in morphology and latency that resulted in age-appropriate latencies by 8 months after implantation. Overall, the development of cortical response latencies for the implanted children was more rapid than for their normal-hearing age-matched peers. Our results demonstrate a high degree of central auditory system plasticity during early human development.

Analysis of Variance↗
PubMed1985

Critical stages for growth in the development of cortical neurons.

In order to study the role of efferent connectivity in the development of CNS neurons, the growth of pyramidal tract neurons within the hamster sensorimotor cortex was studied during normal development and after early postnatal lesions of the pyramidal tract. We first determined, by a combination of Nissl and retrograde HRP techniques, that within the lumbar representation of cortical layer 5B in adult animals two cell populations exist: a large-celled population (40% of the total) projecting to the spinal cord and a small-celled population (60% of the total) projecting intracortically and to targets rostral to the medulla. We could not determine whether large layer 5B cells in the infant sensorimotor cortex also represent the corticospinal population. Nevertheless, measurements of the growth in cross-sectional area of the large cells from 7 days postnatal to adulthood showed that these cells continue to grow until 51 days of age. The most rapid rate of growth occurs between 7 and 14 days, during which time the cross-sectional area of the cell bodies triples, coincident with the arrival of corticospinal axons in the lumbar cord and the beginning of target innervation (Reh and Kalil, '81). The growth of the large neurons in layer 5B was then charted after the pyramidal tract was cut ipsilaterally in the medulla at various postnatal ages. Early lesions of the tract (4-8 days postnatal) interrupt lumbar projection fibers before they establish synapses in the cord. Nevertheless, cortical cell bodies in the lumbar representation continue to grow normally after axotomy until 11 days after birth. At this time, large cells are arrested in development and their cell size remains in the 11-day stage (50% of normal adult large cell size) indefinitely. In contrast, adult lesions of the tract cause a 60% shrinkage of large cells, which in the adult represent corticospinal neurons. No evidence for cortical cell death was found after pyramidal tract lesions at any age. The results of axotomy reveal a turning point in the development of layer 5B cortical neurons. Before the age of 11 days the large cells have an independent program of cell growth that proceeds despite axotomy. After this time, the large cortical neurons appear to require intact axons for further growth and, in the absence of normal connectivity, are arrested in development.

Age Factors↗
PubMed1992

The control of neuronal identity in the developing cerebral cortex.

Recent studies of the lineages and developmental potential of cortical neurons show that cell fates are progressively restricted during cerebral cortical development. Cell lineage experiments suggest that individual cortical precursors are multipotent, as their progeny can end up in different cortical areas, and in different layers within an area. Transplantation studies have shown that young neurons are committed very early on to adopting a given laminar position, in a manner correlated with their birth date in the ventricular zone. Neurons in different neocortical areas, however, retain a functional and anatomical equipotentiality well into cortical development, suggesting that positional cues determine a cell's area-specific identity.

Animals↗
PubMed1999

GABAB receptor-mediated regulation of glutamate-activated calcium transients in hypothalamic and cortical neuron development.

In the mature nervous system excitatory neurotransmission mediated by glutamate is balanced by the inhibitory actions of GABA. However, during early development, GABA acting at the ligand-gated GABAA Cl- channel also exerts excitatory actions. This raises a question as to whether GABA can exert inhibitory activity during early development, possibly by a mechanism that involves activation of the G protein-coupled GABAB receptor. To address this question we used Ca2+ digital imaging to assess the modulatory role of GABAB receptor signaling in relation to the excitatory effects of glutamate during hypothalamic and cortical neuron development. Ca2+ transients mediated by synaptic glutamate release in neurons cultured from embryonic rat were dramatically depressed by the administration of the GABAB receptor agonist baclofen in a dose-dependent manner. The inhibitory effects of GABAB receptor activation persisted for the duration of baclofen administration (>10 min). Preincubation with the Gi protein inhibitor pertussis toxin resulted in a substantial decrease in the inhibitory actions of baclofen, confirming that a Gi-dependent mechanism mediated the effects of the GABAB receptor. Co-administration of the GABAB receptor antagonist 2-hydroxy-saclofen eliminated the inhibitory action of baclofen. Alone, GABAB antagonist application elicited a marked potentiation of Ca2+ transients mediated by glutamatergic neurotransmission, suggesting that tonic synaptic GABA release exerts an inhibitory tone on glutamate receptor-mediated Ca2+ transients via GABAB receptor activation. In the presence of TTX to block action potential-mediated neurotransmitter release, stimulation with exogenously applied glutamate triggered a robust postsynaptic Ca2+ rise that was dramatically depressed (>70% in cortical neurons, >40% in hypothalamic neurons) by baclofen. Together these data suggest both a pre- and postsynaptic component for the modulatory actions of the GABAB receptor. These results indicate a potentially important role for the GABAB receptor as a modulator of the excitatory actions of glutamate in developing neurons.

2-Amino-5-phosphonovalerate↗
PubMed2006

Leptin increases axonal growth cone size in developing mouse cortical neurons by convergent signals inactivating glycogen synthase kinase-3beta.

We examined the effects of the adipose hormone leptin on the development of mouse cortical neurons. Treatment of neonatal and adult mice with intraperitoneal leptin (5 mg/kg) induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in pyriform and entorhinal cortex neurons. Stimulation of cultured embryonic cortical neurons with leptin evoked Janus kinase 2 and ERK1/2 phosphorylation and activated the downstream effector 90-kDa ribosomal protein S6 kinase. Moreover, leptin elicited the phosphorylation of the phosphatidylinositol 3-kinase effector Akt and evoked Ser-9 phosphorylation of glycogen synthase kinase-3beta (GSK3beta), an event inactivating this kinase. Leptin-mediated GSK3beta phosphorylation was prevented by the MEK/ERK inhibitor PD98059, the phosphatidylinositol 3-kinase inhibitor LY294002, or the protein kinase C inhibitor GF109203X. Exposure of cortical neurons to leptin also induced Ser-41 phosphorylation of the neuronal growth-associated protein GAP-43, an effect prevented by LY294002 and GF109203X but not by PD98059. Ser-41-GAP-43 phosphorylation is usually high in expanding axonal growth cones. Neurons exposed to 100 ng/ml leptin for 72 h displayed reduced rate of growth cone collapse, a shift of growth cone size distribution toward higher values, and a 4-fold increase in mean growth cone surface area compared with control cultures. The leptin-induced growth cone spreading was hampered in cortical neurons from Lepr(db/db) mice lacking functional leptin receptors; it was associated with localized Ser-9-GSK3beta phosphorylation and mimicked by the GSK3beta inhibitor SB216763. At concentrations preventing GSK3beta phosphorylation, PD98059, LY294002, or GF109203X reversed the leptin-induced growth cone surface enlargement. We concluded that the leptin-mediated regulation of growth cone morphogenesis in cortical neurons relies on upstream regulators of GSK3beta activity.

Animals↗
PubMed1982

Selective collateral elimination in early postnatal development restricts cortical distribution of rat pyramidal tract neurones.

The pyramidal tract, comprising those axons which pass from the neocortex to the medulla and spinal cord, is among the most thoroughly studied projections of the mammalian cortex. Recent studies using anterograde axon tracing techniques have provided information concerning the time course of the growth of pyramidal tract fibres, yet much remains to be learned about its development. We have now begun to study the distribution of the neurones of origin of the pyramidal tract during the postnatal development of the rat neocortex using the recently introduced retrogradely transported fluorescent marker, True blue. During the first postnatal week, injections of True blue into the pyramidal decussation result inthe labelling of pyramidal tract neurones which are distributed virtually throughout the tangential extent of layer V of the neocortex, whereas after comparable injections during the fourth postnatal week the distribution of such cells is much more restricted and remains restricted into adult life. This developmental restriction is most dramatic in the occipital cortex: during the first postnatal week many pyramidal tract neurones are found throughout the visual cortex while none is seen in this area of the adult. When True blue is injected into the pyramidal decussation during the first postnatal week and the animals are allowed to survive until the fourth postnatal week, the distribution of pyramidal tract neurones is as widespread as in the immediate postnatal period and includes the entire visual cortex. This implies that many of the neurones in the occipital cortex initially send a collateral into the pyramidal tract which is later eliminated, although the neurones themselves persist. These findings, together with similar recent observations on the development of the callosal connections, indicate that the elimination of axon collaterals may be a general feature of the development of cortical projection systems, and that such transitory collaterals may traverse considerable distances.

Animals↗
PubMed2003

Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex.

LIM-homeodomain (LIM-HD) genes encode a family of transcription factors known to be involved in development and patterning in several systems. Previously, we have shown that LIM-HD gene Lhx2 is required for the formation of a crucial boundary in the dorsal telencephalon (Bulchand et al. [2001] Mech Dev 100:165-175). To further explore the role of LIM-HD genes as well as the broader LIM gene family in dorsal telencephalic development, we examined the expression pattern of the members of this gene family and their cofactors in the developing mouse cerebral cortex. Transcription factor activity of the LIM-HD proteins requires the formation of a tetrameric complex consisting of two LIM-HD molecules linked by a dimer of cofactor (Clim) molecules. LIM-only (Lmo) proteins can interfere with this process by competing for the cofactors. LIM-HD protein function, thus, can be modulated by the presence of the appropriate Clim or Lmo molecules. At least 13 LIM-HD, 4 Lmo, and 2 Clim genes have been identified in the mouse. Several of these genes exhibit complex spatiotemporal patterns spanning different stages of cortical development, from embryonic to postnatal ages. Noteworthy features of the expression patterns include delineation of boundaries within the developing cortex, up- or down-regulation during formation of selected cortical layers, and a striking complementarity of expression of several members consistent with specific functions in cortical development. Significantly, in some cases, Lmo or Clim gene expression is robust where no LIM-HD gene expression is detectable. These results suggest multiple and distinct roles for LIM-HD, Lmo, and Clim genes in cortical development, and also support a LIM-HD-independent role for some Lmo and Clim members.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Differential regulation of c-fos expression after cortical brain injury during development.

Unilateral cortical brain injury is accompanied by widespread expression of c-fos protein(s) throughout the wounded cortex, including areas far from the lesion site. Here we report that this phenomenon is differentially regulated during development. At postnatal day (PD) 10 or 15, when rats were sacrificed 1.5 h after a mechanical cortical injury, they did not show an increase in c-fos immunoreactivity far from the wound, despite the fact that some of these animals (PD 15) displayed a positive response close to the lesion. At PD 22, the same injury induced an increase in c-fos-immunoreactive nuclei in the piriform cortex ipsilateral, but not contralateral, to the lesion. This pattern was maintained up to at least PD 360. Similarly, the presence of c-fos-immunoreactive cells was observed in the ipsilateral cingulate cortex in animals 22 days old and older. The pattern of c-fos expression in adult animals after mechanical damage was compared with other models of focal brain injury: application of potassium to the cortical surface and devascularization. Though all models generated c-fos expression far from the lesion site, potassium application resulted in higher numbers of c-fos-positive cells, particularly in the cingulate cortex. This study shows that c-fos expression after cortical brain injury is regulated differently during development, and that dissimilar models of cortical injury induce qualitatively similar responses although c-fos-like protein expression differs quantitatively.

Animals↗
PubMed2001

Modular transport of postsynaptic density-95 clusters and association with stable spine precursors during early development of cortical neurons.

The properties of filopodia and spines and their association with the postsynaptic density (PSD) protein PSD-95 were studied during early development of cultured cortical neurons using time-lapse confocal microscopy. Neurons were transfected with recombinant PSD-95 constructs fused to green fluorescent protein (GFP) for, on average, either 8 d in vitro (DIV) or 14 DIV. We find that, during 1 hr of imaging, filopodia and spines bearing PSD-95/GFP clusters are significantly more stable (i.e., do not turnover) than those lacking clusters. When present within a spine precursor, a PSD-95/GFP cluster appeared to nucleate a relatively stable structure around which filopodium-spine membranes can move. Although processes bearing clusters were generally stable, in 8 DIV neurons, we observed that a subset ( approximately 10%) of PSD-95/GFP clusters underwent rapid modular translocation between filopodia-spines and dendritic shafts. We conclude that, during early synaptic maturation, prefabricated PSD-95 clusters are trafficked in a developmentally regulated process that is associated with filopodial stabilization and synapse formation.

Animals↗
PubMed2003

Genetic disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy, and behavioral dysfunction.

The generation of properly functioning circuits during brain development requires precise timing of cell migration and differentiation. Disruptions in the developmental plan may lead to neurological and psychiatric disorders. Neocortical circuits rely on inhibitory GABAergic interneurons, the majority of which migrate from subcortical sources. We have shown that the pleiotropic molecule hepatocyte growth factor/scatter factor (HGF/SF) mediates interneuron migration. Mice with a targeted mutation of the gene encoding urokinase plasminogen activator receptor (uPAR), a key component in HGF/SF activation and function, have decreased levels of HGF/SF and a 50% reduction in neocortical GABAergic interneurons at embryonic and perinatal ages. Disruption of interneuron development leads to early lethality in most models. Thus, the long-term consequences of such perturbations are unknown. Mice of the uPAR-/- strain survive until adulthood, and behavior testing demonstrates that they have an increased anxiety state. The uPAR-/- strain also exhibits spontaneous seizure activity and higher susceptibility to pharmacologically induced convulsions. The neocortex of the adult uPAR-/- mouse exhibits a dramatic region- and subtype-specific decrease in GABA-immunoreactive interneurons. Anterior cingulate and parietal cortical areas contain 50% fewer GABAergic interneurons compared with wild-type littermates. However, interneuron numbers in piriform and visual cortical areas do not differ from those of normal mice. Characterization of interneuron subpopulations reveals a near complete loss of the parvalbumin subtype, with other subclasses remaining intact. These data demonstrate that a single gene mutation can selectively alter the development of cortical interneurons in a region- and cell subtype-specific manner, with deficits leading to long-lasting changes in circuit organization and behavior.

Animals↗
PubMed2006

The development of cortical multisensory integration.

Although there are many perceptual theories that posit particular maturational profiles in higher-order (i.e., cortical) multisensory regions, our knowledge of multisensory development is primarily derived from studies of a midbrain structure, the superior colliculus. Therefore, the present study examined the maturation of multisensory processes in an area of cat association cortex [i.e., the anterior ectosylvian sulcus (AES)] and found that these processes are rudimentary during early postnatal life and develop only gradually thereafter. The AES comprises separate visual, auditory, and somatosensory regions, along with many multisensory neurons at the intervening borders between them. During early life, sensory responsiveness in AES appears in an orderly sequence. Somatosensory neurons are present at 4 weeks of age and are followed by auditory and multisensory (somatosensory-auditory) neurons. Visual neurons and visually responsive multisensory neurons are first seen at 12 weeks of age. The earliest multisensory neurons are strikingly immature, lacking the ability to synthesize the cross-modal information they receive. With postnatal development, multisensory integrative capacity matures. The delayed maturation of multisensory neurons and multisensory integration in AES suggests that the higher-order processes dependent on these circuits appear comparatively late in ontogeny.

Aging↗
PubMed2005

Regional, laminar and cellular distribution of immunoreactivity for ERbeta in the cerebral cortex of hormonally intact, postnatally developing male and female rats.

Estrogen influences cerebral cortical development. Among the receptors involved are classical (ERalpha) and beta (ERbeta) intracellular estrogen receptors. In the first 2 weeks of postnatal life, cortical ERalpha is transiently expressed at much higher levels than in adulthood. In this study, development of ERbeta was examined by mapping ERbeta immunoreactivity in relation to major cortical regions, layers and cell types in postnatal male and female rats that were 1-28 postnatal days (PND) old. These studies revealed that ERbeta-immunoreactive nuclei were present in the allocortices on PND 1 but were not detected in isocortex until PND 7. Allocortical labeling was also higher on PND 1 than at all later ages, while in isocortical areas low numbers of ERbeta nuclei were seen on PND 7 that rose to higher, near adult densities by PND 21. Finally, double labeling showed that ERalpha was expressed mainly in neurons immunopositive for calretinin, while ERbeta was localized predominantly in parvalbumin-immunoreactive cells. Thus, the postnatal cortical developments of ERbeta and ERalpha occur according to different timetables, different patterns and in association with different cortical cells. It thus seems it likely that the two also make distinct contributions to postnatal cortical development and/or sexual differentiation.

Aging↗
PubMed1990

Development of cortical vesicles in Sicyonia ingentis ova: their heterogeneity and role in elaboration of the hatching envelope.

In the marine shrimp Sicyonia ingentis, ova lack cortical vesicles at spawning. Previous ultrastructural studies suggested that two different populations of cortical vesicles (dense vesicles and the ring vesicles) appear within 30 min post-spawning. These vesicles undergo sequential exocytosis (exocytosis of the dense vesicles followed by exocytosis of the ring vesicles) that leads to the formation of a hatching envelope around the ovum (see Pillai and Clark: Tissue & Cell 20:941-52, 1988). In the present study, lectins were used as molecular probes to study the development of cortical vesicles subsequent to spawning and the role of these vesicles in formation and elaboration of the hatching envelope. Isolated envelopes were screened with 11 different lectins to determine what group(s) were specific to the envelope glycoconjugates; Concanavalin A (Con A), Griffonia simplicifolia (GS II), Lens culinaris (LCA), and wheat germ agglutinin (WGA) bound to the envelopes. FITC-lectin studies of sectioned ova (fixed at various time points after spawning) utilizing WGA and LCA showed different labelling patterns. Data obtained at the light microscopical level indicated that WGA was specific to the dense vesicles and the outer portion of the envelope, while LCA exhibited specificity for the ring vesicles and the inner portion of the envelope. At the ultrastructural level, gold-LCA labelling was seen associated with the cisternal elements (containing ring-shaped structures), ring vesicles, and the inner layer of the fully formed envelope. These data demonstrated that 1) the ring vesicles are formed by fusion of cisternal elements containing ring-shaped structures; 2) the two species of cortical vesicles are chemically heterogeneous; and 3) the components of each type of vesicle contribute to different integral parts (the outer and inner layers) of the hatching envelope.

Animals↗
PubMed2002

Molecular control of cortical dendrite development.

Dendritic morphology has a profound impact on neuronal information processing. The overall extent and orientation of dendrites determines the kinds of input a neuron receives. Fine dendritic appendages called spines act as subcellular compartments devoted to processing synaptic information, and the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma. The acquisition of a mature dendritic morphology depends on the coordinated action of a number of different extracellular factors. Here we discuss this evidence in the context of dendritic development in the cerebral cortex. Soon after migrating to the cortical plate, neurons extend an apical dendrite directed toward the pial surface. The oriented growth of the apical dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant. Subsequent dendritic development involves signaling by neurotrophic factors and Notch, which regulate dendritic growth and branching. During postnatal development the formation and stabilization of dendritic spines are regulated in part by patterns of synaptic activity. These observations suggest that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.

Animals↗
PubMed2004

Dissociation of experience-dependent and -independent changes in excitatory synaptic transmission during development of barrel cortex.

A fundamental problem in the study of cortical development is the extent to which the formation and refinement of synaptic circuitry depends upon sensory experience. The barrel cortex is a useful model system to study experience-dependent cortical development because there is a simple mapping of individual whiskers to the corresponding barrel columns in the cortex. We investigated experience-dependent and -independent changes in glutamatergic synaptic transmission in the barrel cortex during the second postnatal week by comparing synaptic responses from whisker-intact mice at postnatal day (P) 7 and P14 with those from whisker-deprived mice at P14. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)-receptor-mediated excitatory synaptic responses were recorded from layer 2/3 pyramidal cells in vitro during voltage-clamp in response to stimulation in layer 4. We observed that the ratio of synaptic AMPA- to NMDA-receptor-mediated current (A/N ratio) increased with developmental age. The development of the A/N ratio was unchanged by deprivation of the whisker input throughout the second postnatal week. In contrast, the NMDA-receptor current decay and sensitivity to the NMDA receptor 2B subunit-selective antagonist ifenprodil was affected strongly by such deprivation. These results demonstrate a concurrent dissociation between sensory experience-dependent and -independent changes of glutamatergic transmission in the barrel cortex during the second postnatal week. Furthermore, they suggest that the development of subunit composition of synaptic receptors is dependent on sensory experience, whereas maturation of the synaptic A/N ratio is independent of such experience. Thus, different components of synaptic development may be governed by different developmental rules.

Animals↗
PubMed2005

Abnormal neocortical development in mice lacking cGMP-dependent protein kinase I.

Cyclic GMP-dependent protein kinase type I (cGKI) is a key signaling intermediate important for synaptic potentiation in the hippocampus and cerebellum, but its expression and function in cortical development have not been elucidated. The expression of cGKI in the developing mouse neocortex was evaluated by immunofluorescence labeling, and effect of cGKI deletion on cortical development was studied in adult cGKI knockout mice. cGKI was expressed at highest levels at embryonic stages in young neurons and radial glial fibers, corresponding to the major period of radial migration and laminar development of pyramidal neurons (embryonic day E13.5-E14.5), declining upon maturation (E17.5-postnatal day P28). The cerebral cortex of homozygous null mutant mice lacking cGKI exhibited heterotopic collections of neurons in the upper cortical layers and abnormal invaginations of layer I, in accord with a neuronal migration or positioning defect. Some cGKI mutant mice displayed defects in midline development resulting in partial fusion of cerebral hemispheres with adjacent neuronal heterotopias. Apical dendrites of cortical pyramidal neurons were misoriented in the cerebral cortex of cGKI null mutants, as shown in reporter mice expressing yellow fluorescent protein in layer V pyramidal neurons and by Golgi impregnation. These results demonstrate a role for cGKI signaling in cortical development related to neuronal migration/positioning that is important for dendritic orientation and connectivity.

Animals↗
PubMed2004

[Protection of interleukin-1 receptor antagonist on epileptiform discharges induced by magnesium-free treatment in developing rat cortical neurons].

OBJECTIVE: To study the protection of IL-1ra in cultured developing neuron injury following Mg(2+)-free-induced epileptiform discharges. METHODS: Rat embryo cortical neurons cultured for 6 d and 17 d were directly exposed to Mg(2+)-free media, or pretreated with IL-1 receptor antagonist or NMDA receptor antagonists before being exposed to Mg(2+)-free media, and then returned to regular media.MTT assay was used to study mitochondrial function injury, laser-scanning confocal microscope to measure [Ca(2+)]i, and real-time RT-PCR to detect gene mRNA expression. RESULTS: (1) MTT conversion rates were higher in neurons pre and co treated with 10 mg/L IL-1ra than those of neurons with only Mg(2+)-free treatment in neurons cultured for 17 d, but not in neurons cultured for 6 d.(2) [Ca(2+)]i was lower in neurons pre and co-treated with 10 mg/L IL-1ra than those of neurons with only Mg(2+)-free treatment, either in neurons cultured for 6 d or in neurons cultured for 17 d, and the effects of IL-1ra on [Ca(2+)]i change were different between neurons cultured for 6 d and neurons cultured for 17 d.(3) Pre and co-treated with 10 mg/L IL-1ra NR1 mRNA expression increase induced by Mg(2+)-free treatment was decreased, either in neurons cultured for 6 d or neurons cultured for 17 d, and this effect showed no difference between neurons cultured for 6 d and 17 d; Pre and co-treated with 10 mg/L IL-1ra NR2A mRNA expression increase induced by Mg(2+)-free treatment in neurons cultured for 17 d was decreased, and NR2A mRNA expression showed no difference between IL-1ra group and age-matched control group, but have no effect on neurons cultured for 6 d; Pre and co-treated with 10 mg/L IL-1ra have NR2B mRNA expression increase induced by Mg(2+)-free treatment was not affected, either in neurons cultured for 6 d or neurons cultured for 17 d. CONCLUSION: Neuroprotection of IL-1Ra in seizure-induced injury is age-dependent. The mech-anism of the neuroprotection of IL-1Ra includes down-regulation of [Ca(2+)]i and others.

Animals↗