Early Stages Of Postnatal Development Research Articles

Hub GABA Neurons Mediate Gamma-Frequency Oscillations at Ictal-like Event Onset in the Immature Hippocampus

Gamma-frequency oscillations (GFOs, >40Hz) are a general network signature at seizure onset at all stages of development, with possible deleterious consequences in the immature brain. At early developmental stages, the simultaneous occurrence of GFOs in different brain regions suggests the existence of a long-ranging synchronizing mechanism at seizure onset. Here, we show that hippocamposeptal (HS) neurons, which are GABA long-range projection neurons, are mandatory to drive the firing of hippocampal interneurons in a high-frequency regime at the onset of epileptiform discharges in the intact, immature septohippocampal formation. The synchronized firing of interneurons in turn produces GFOs, which are abolished after the elimination of a small number of HS neurons. Because they provide the necessary fast conduit for pacing large neuronal populations and display intra- and extrahippocampal long-range projections, HS neurons appear to belong to the class of hub cells that play a crucial role in the synchronization of developing networks.

A nest ofProtoceratops andrewsi(Dinosauria, Ornithischia)

A remarkable specimen of the small neoceratopsian dinosaurProtoceratops andrewsi(Late Cretaceous, Mongolia) reveals the first nest of this genus, complete with fifteen juveniles. The relatively large size of the individuals and their advanced state of development suggests the possibility thatProtoceratopsjuveniles remained and grew in their nests during at least the early stages of postnatal development. The nest further implies that parental care and sociality are phylogenetically basal behaviors in Ceratopsia. Finally, it reaffirms the conclusion thatProtoceratopslived (and died) in the sandy aeolian dune fields of the central Asian craton.

Developmental Sculpting of Dendritic Morphology of Layer 4 Neurons in Visual Cortex: Influence of Retinal Input

Dendritic morphology determines the kinds of input a neuron receives, having a profound impact on neural information processing. In the mammalian cerebral cortex, excitatory neurons have been ascribed to one of two main dendritic morphologies, either pyramidal or stellate, which differ mainly on the extent of the apical dendrite. Developmental mechanisms regulating the emergence and refinement of dendritic morphologies have been studied for cortical pyramidal neurons, but little is known for spiny stellate neurons. Using biolistics to label single cells on acute brain slices of the ferret primary visual cortex, we show that neurons in layer 4 develop in a two-step process: initially, all neurons appear pyramidal, growing a prominent apical dendrite and few small basal dendrites. Later, a majority of these neurons show a change in the relative extent of basal and apical dendrites that results in a gradual sculpting into a stellate morphology. We also find that ∼ 22% of neurons maintain the proportionality of their dendritic arbors, remaining as pyramidal cells at maturity. When ferrets were deprived of retinal input at early stages of postnatal development by binocular enucleation, a significant proportion of layer 4 spiny neurons failed to remodel their apical dendrites, and ∼ 55% remained as pyramidal neurons. Our results demonstrate that cortical spiny stellate neurons emerge by differential sculpting of the dendritic arborizations of an initial pyramidal morphology and that sensory input plays a fundamental role in this process.

Oxidative Modifications of the C-terminal Domain of Tropoelastin Prevent Cell Binding

Tropoelastin (TE), the soluble monomer of elastin, is synthesized by elastogenic cells, such as chondrocytes, fibroblasts, and smooth muscle cells (SMCs). The C-terminal domain of TE interacts with cell receptors, and these interactions play critical roles in elastic fiber assembly. We recently found that oxidation of TE prevents elastic fiber assembly. Here, we examined the effects of oxidation of TE on cell interactions. We found that SMCs bind to TE through heparan sulfate (HS), whereas fetal lung fibroblasts (WI-38 cells) bind through integrin α(v)β(3) and HS. In addition, we found that oxidation of TE by peroxynitrite (ONOO(-)) prevented binding of SMCs and WI-38 cells and other elastogenic cells, human dermal fibroblasts and fetal bovine chondrocytes. Because the C-terminal domain of TE has binding sites for both HS and integrin, we examined the effects of oxidation of a synthetic peptide derived from the C-terminal 25 amino acids of TE (CT-25) on cell binding. The CT-25 peptide contains the only two Cys residues in TE juxtaposed to a cluster of positively charged residues (RKRK) that are important for cell binding. ONOO(-) treatment of the CT-25 peptide prevented cell binding, whereas reduction of the CT-25 peptide had no effect. Mass spectrometric and circular dichroism spectroscopic analyses showed that ONOO(-) treatment modified both Cys residues in the CT-25 peptide to sulfonic acid derivatives, without altering the secondary structure. These data suggest that the mechanism by which ONOO(-) prevents cell binding to TE is by introducing negatively charged sulfonic acid residues near the positively charged cluster.

Life of mice - development of cardiac energetics

Life of mice - development of cardiac energetics

Differential expression of PACAP receptors in postnatal rat brain

Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) is a multi-functional neuropeptide that acts through activation of three common G-protein coupled receptors (VPAC1, VPAC2 and PAC1). In this study, we have investigated the gene expression profile of PAC1 isoforms (Hop1, Hip, Hip-Hop) and VPAC1, VPAC2 receptors in distinct brain regions during different stages of rat postnatal development. Using quantitative real time PCR approach we found that PAC1 isoforms were highly expressed in the cortex of newborns with marked decrease in expression during later stages of development. In contrast, mRNA levels of VPAC1, VPAC2 receptors were markedly lower in newborns in comparison to later developmental stages. Expression of PAC1 isoforms predominated in the hippocampus, while expression of VPAC1 was more prominent in the cortex and VPAC2 in the striatum and hippocampus. In addition we found that during early stages of postnatal development the expression of PAC1 receptor in the hippocampus was significantly higher in females than in males. No sex dependent differences in expression were observed for the VPAC1 and VPAC2 receptors. In summary, differential expression of PAC1, VPAC1 and VPAC2 receptors during postnatal development as well as gender dependent differences of PAC1 receptor expression in the hippocampus, will contribute to our understanding of the role of PACAP/VIP signaling system in normal brain development and function.

Effect of Toluene Intoxication on Spatial Behavior and Learning of Rats within Early Stages of Postnatal Development

Toluene inhalation-induced intoxication (500 ррm) of albino mongrel rats within early stages of postnatal development (to postnatal day Р30) significantly suppressed realization of auriculonasocephalic reflex within the time interval preceding the period of beginning of visual perception, i.e., eye opening in young animals (Р7 to Р13). Later on (Р15 and Р21), we observed a drop in the motivation level and disorders of learning processes in the course of testing in a water corridor. Results of testing of a passive avoidance reaction after toluene intoxication during Р30 indicated that the ability of intoxicated animals to consolidate memory traces noticeably decreased.

TLR2 activation inhibits embryonic neural progenitor cell proliferation

Toll-like receptors (TLRs) play essential roles in innate immunity, and increasing evidence indicates that these receptors are expressed in neurons, astrocytes, and microglia in the brain, where they mediate responses to infection, stress, and injury. To address the possibility that TLR2 heterodimer activation could affect progenitor cells in the developing brain, we analyzed the expression of TLR2 throughout mouse cortical development, and assessed the role of TLR2 heterodimer activation in neuronal progenitor cell (NPC) proliferation. TLR2 mRNA and protein was expressed in the cortex in embryonic and early postnatal stages of development, and in cultured cortical NPC. While NPC from TLR2-deficient and wild type embryos had the same proliferative capacity, TLR2 activation by the synthetic bacterial lipopeptides Pam(3)CSK(4) and FSL1, or low molecular weight hyaluronan, an endogenous ligand for TLR2, inhibited neurosphere formation in vitro. Intracerebral in utero administration of TLR2 ligands resulted in ventricular dysgenesis characterized by increased ventricle size, reduced proliferative area around the ventricles, increased cell density, an increase in phospho-histone 3 cells, and a decrease in BrdU(+) cells in the sub-ventricular zone. Our findings indicate that loss of TLR2 does not result in defects in cerebral development. However, TLR2 is expressed and functional in the developing telencephalon from early embryonic stages and infectious agent-related activation of TLR2 inhibits NPC proliferation. TLR2-mediated inhibition of NPC proliferation may therefore be a mechanism by which infection, ischemia, and inflammation adversely affect brain development.

Effects of Ethanol on Neuron Density in the Limbic Cortex of the Brain and Correction of Evoked Changes with the Antioxidant Dolivin

The aims of the present work were to measure neuron density in the limbic cortex in the offspring of female white rats given 15% ethanol solution during pregnancy and lactation and to address the possibility of correcting ethanol-induced impairments at the early stages of postnatal development (PND) using the antioxidant Dolivin. Neuron numbers were measured in the cingulate gyrus and entorhinal cortex on PND days 3, 7, 15, 21, and 30 (three animals in each age group). Dolivin (0.7 mg) was added to the diets of female animals with the aim of preventing ethanol-induced changes. The cytotoxic action of ethanol was found to decrease the total number of cells in the limbic cortex at the early stages of PND, particularly on day 7. Neurons in the deep part of the limbic zone were the most sensitive to the actions of ethanol. Dolivin had preventative effects, weakening the cytotoxic actions of ethanol at all stages of development.

8. Experimental epileptic encephalopathies

It is very difficult to model age-dependent epileptic encephalopathies because they represent very complex syndromes. We started to model one of the symptoms – flexion seizures – in the early nineties [ [1] Mareš P, Velíšek L. Dev Brain Res 1992;65:185–9. Google Scholar ]. These seizures could be elicited by administration of drugs acting as agonists on N-methyl-D-aspartate type of glutamate receptors during the first two weeks of postnatal life in rats. This age corresponds to perinatal and early postnatal (up to preschool age) developmental stages of the human brain. Based on flexion seizures, two models of epileptic encephalopathies exhibiting more characteristic symptoms were elaborated. Both models work with animals that are exposed to the first insult during early development; it is then possible to elicit model seizures in damaged animals. A model published in 2007 used prenatal administration of betamethasone and a postnatal (day 15) intraperitoneal injection of N-methyl-D-aspartate [ [4] Velísek L, Jehle K, Asche S, Velísková J. Ann Neurol 2007;61:109—19. Google Scholar ]. Another model from the same laboratory uses lipopolysaccharide and doxorubicin injected intracerebrally at postnatal day 3 and p-chlorophenylalanine at postnatal day 5 [ [3] Scantlebury MH, Galanopoulou AS, Chudomelova L, Raffo E, Betancourth D, Moshé SL. Neurobiol Dis 2010;37:604– 12. Google Scholar ]. These rat models also exhibit ictal and interictal EEG abnormalities and developmental decline typical for early-age human epileptic encephalopathies. A new genetic mouse model elaborated by expansion of the Arx gene exhibits spontaneous seizures including infantile spasms and cognitive and behavioral impairment persisting up to adulthood [ [2] Price MG, Yoo JW, Burgess DL, Deng F, Hrachovy RA, Frost Jr JD, et al. J Neurosci 2009;29:8752–63. Google Scholar ]. The last two models are promising but they have to be further analyzed.

Categorical Representation of Facial Expressions in the Infant Brain

Categorical perception, demonstrated as reduced discrimination of within-category relative to between-category differences in stimuli, has been found in a variety of perceptual domains in adults. To examine the development of categorical perception in the domain of facial expression processing, we used behavioral and event-related potential (ERP) methods to assess discrimination of within-category (happy-happy) and between-category (happy-sad) differences in facial expressions in 7-month-old infants. Data from a visual paired-comparison test and recordings of attention-sensitive ERPs showed no discrimination of facial expressions in the within-category condition whereas reliable discrimination was observed in the between-category condition. The results also showed that face-sensitive ERPs over occipital-temporal scalp (P400) were attenuated in the within-category condition relative to the between-category condition, suggesting a potential neural basis for the reduced within-category sensitivity. Together, these results suggest that the neural systems underlying categorical representation of facial expressions emerge during the early stages of postnatal development, before acquisition of language.

Alcian Blue/Alizarin Red Staining of Cartilage and Bone in Mouse: Figure 1.

INTRODUCTIONThe vertebrate skeleton forms by endochondral and intramembranous bone formation. During endochondral bone formation, mesenchyme condensations give rise to cartilages that are eventually replaced by bone. However, there are some permanent cartilages that do not ossify, such as the cartilage of the trachea and articular cartilage of the joints, and intramembranous bone formation occurs directly without a cartilage template. This article describes a method for simultaneously visualizing cartilage and mineralized tissues (notably bone) in the developing mouse. It makes use of alcian blue and alizarin red stains, and it is best used for later fetal, newborn, and early post-natal stages of development. Neonatal skeletons are especially well suited for this technique.

The α-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model of Charcot–Marie–Tooth disease type 1A and alters myelin gene expression in cultured Schwann cells

At present the pathogenesis of CMT1A neuropathy, caused by the overexpression of PMP22, has not yet been entirely understood. The PMP22-overexpressing C61 mutant mouse is a suitable animal model, which mimics the human CMT1A disorder. We observed that myelin gene expression in the sciatic nerve of the C61 mouse was up-regulated at postnatal day 4 to 7 (P4–P7). When investigating the morphology of peripheral nerves in C61 and wildtype mice at early stages of postnatal development, hypermyelination could be detected in the femoral quadriceps and sciatic nerve of transgenic animals at postnatal day 7 (P7). In order to identify genes, other than Pmp22, that are modulated in sciatic nerve of P7 transgenic mice, we applied microarray technology. Amongst the regulated genes, the gene encoding the α-chemokine CXCL14 was most prominently up-regulated. We report that Cxcl14 was expressed exclusively by Schwann cells of the sciatic nerve, as well as by cultured Schwann cells triggered to differentiate. Furthermore, in cultured Schwann cells CXCL14 modulated the expression of myelin genes and altered cell proliferation. Our findings demonstrate that early overexpression of PMP22, in a mouse model of CMT1A, results in a strong up-regulation of CXCL14, which seems to play a novel regulatory role in Schwann cell differentiation.

Development and Plasticity of Intra- and Intersensory Information Processing

The functional architecture of sensory brain regions reflects an ingenious biological solution to the competing demands of a continually changing sensory environment. While they are malleable, they have the constancy necessary to support a stable sensory percept. How does the functional organization of sensory brain regions contend with these antithetical demands? Here we describe the functional organization of auditory and multisensory (i.e., auditory-visual) information processing in three sensory brain structures: (1) a low-level unisensory cortical region, the primary auditory cortex (A1); (2) a higher-order multisensory cortical region, the anterior ectosylvian sulcus (AES); and (3) a multisensory subcortical structure, the superior colliculus (SC). We then present a body of work that characterizes the ontogenic expression of experience-dependent influences on the operations performed by the functional circuits contained within these regions. We will present data to support the hypothesis that the competing demands for plasticity and stability are addressed through a developmental transition in operational properties of functional circuits from an initially labile mode in the early stages of postnatal development to a more stable mode in the mature brain that retains the capacity for plasticity under specific experiential conditions. Finally, we discuss parallels between the central tenets of functional organization and plasticity of sensory brain structures drawn from animal studies and a growing literature on human brain plasticity and the potential applicability of these principles to the audiology clinic.

CDKL5 Expression Is Modulated during Neuronal Development and Its Subcellular Distribution Is Tightly Regulated by the C-terminal Tail

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in patients with Rett syndrome (RTT), West syndrome, and X-linked infantile spasms, sharing the common feature of mental retardation and early seizures. CDKL5 is a rather uncharacterized kinase, but its involvement in RTT seems to be explained by the fact that it works upstream of MeCP2, the main cause of Rett syndrome. To understand the role of this kinase for nervous system functions and to address if molecular mechanisms are involved in regulating its distribution and activity, we studied the ontogeny of CDKL5 expression in developing mouse brains by immunostaining and Western blotting. The expression profile of CDKL5 was compared with that of MeCP2. The two proteins share a general expression profile in the adult mouse brain, but CDKL5 levels appear to be highly modulated at the regional level. Its expression is strongly induced in early postnatal stages, and in the adult brain CDKL5 is present in mature neurons, but not in astroglia. Interestingly, the presence of CDKL5 in the cell nucleus varies at the regional level of the adult brain and is developmentally regulated. CDKL5 shuttles between the cytoplasm and the nucleus and the C-terminal tail is involved in localizing the protein to the cytoplasm in a mechanism depending on active nuclear export. Accordingly, Rett derivatives containing disease-causing truncations of the C terminus are constitutively nuclear, suggesting that they might act as gain of function mutations in this cellular compartment.

SCLIP Is Crucial for the Formation and Development of the Purkinje Cell Dendritic Arbor

Cerebellar Purkinje cells elaborate one of the most complex dendritic arbors among neurons to integrate the numerous signals they receive from the cerebellum circuitry. Their dendritic differentiation undergoes successive, tightly regulated phases of development involving both regressive and growth events. Although many players regulating the late phases of Purkinje cell dendritogenesis have been identified, intracellular factors controlling earlier phases of dendritic development remain mostly unknown. In this study, we explored the biological properties and functions of SCLIP, a protein of the stathmin family, in Purkinje cell dendritic differentiation and cerebellum development. Unlike the other stathmins, SCLIP is strongly expressed in Purkinje cells during cerebellar development and accumulates in their dendritic processes at a critical period of their formation and outgrowth. To reveal SCLIP functions, we developed a lentiviral-mediated approach on cerebellar organotypic cultures to inhibit or increase its expression in Purkinje cells in their tissue environment. Depletion of SCLIP promoted retraction of the Purkinje cell primitive process and then prevented the formation of new dendrites at early stages of postnatal development. It also prevented their elongation and branching at later phases of differentiation. Conversely, SCLIP overexpression promoted dendritic branching and development. Together, our results demonstrate for the first time that SCLIP is crucial for both the formation and proper development of Purkinje cell dendritic arbors. SCLIP appears thus as a novel and specific factor that controls the early phases of Purkinje cell dendritic differentiation during cerebellum development.

The effect of intentional cranial deformation on frontal sinus development and morphology

Introduction: Intentional cranial deformation (ICD) has been documented to be a world‐wide phenomenon whose practice elicits considerable shape changes to the neurocranium during the early stages of postnatal development. Since the development of the frontal sinuses begins after early childhood, the application of ICD procedures should affect morphological growth trajectories in its anatomy. This qualitative and quantitative study examines the effects of ICD on the frontal sinus development and morphology.Methods: Twenty intentionally deformed (ID) and twenty non‐deformed (ND) dry crania from distinct Bolivian and Peruvian indigenous populations were selected from the Division of Anthropology at the American Museum of Natural History. The crania were scanned using a hispeed helical CT scanner. Craniofacial linear measures, along with endocranial (EC) and frontal sinus volumetric determinations were obtained using a three dimensional (3‐D) volume rendering program.Results: 3‐D reconstructed volumetric studies showed no statistical differences between the EC volume of ID and ND crania. Analysis of frontal angle showed statistically significant difference between ID and ND crania (p<0.001). Volumetric measurements of frontal sinus showed no statistically significant differences between ID and ND crania.Conclusion: ICD procedures affect more readily the extrasplanchnocranial moiety as detected by external linear measurements of adult crania. However, the development of the frontal sinus seems not to be affected by these external changes. This study emphasizes the developmental potential of the paranasal sinuses which is not affected by structural changes within the neurocranium.

Anandamide Regulates Postnatal Development of Long-Term Synaptic Plasticity in the Rat Dorsolateral Striatum

Long-term changes in synaptic efficacy produced by high-frequency stimulation (HFS) of glutamatergic afferents to the rat dorsolateral striatum exhibit heterogeneity during early stages of postnatal development. Whereas HFS most often induces striatal long-term potentiation (LTP) in rats postnatal day 12 (P12)-P14, the same stimulation tends to induce long-term depression (LTD) at ages P16-P34. Previous studies have shown that striatal LTD induction depends on retrograde endocannabinoid signaling and activation of the CB1 cannabinoid receptor. It is also known that levels of one of the primary endogenous CB1 receptor agonists, anandamide (AEA), increases during development in whole-brain samples. In the present study, we sought to determine whether this developmental increase in AEA also takes place in striatal tissue and whether increased AEA levels contribute to the postnatal switch in the response to HFS. We observed a pronounced increase in striatal levels of AEA, but not the other major endogenous cannabinoid 2-arachidonoylglycerol (2-AG), during the postnatal period characterized by the switch from LTP to LTD. Furthermore, application of synthetic AEA during HFS in field recordings of slices from P12-P14 rats allowed for induction of LTD whereas blocking the CB1 receptor during HFS in animals P16-P34 resulted in expression of LTP. However, blocking 2-AG synthesis with the DAG-lipase inhibitor tetrahydrolipstatin did not alter HFS-induced striatal LTD. In addition, synaptic depression produced by a synthetic CB1 agonist was similar across development. Together, these findings suggest that the robust developmental increase in striatal AEA may be the key factor in the emergence of HFS-induced striatal LTD.

Cellular distribution of γ-secretase subunit nicastrin in the developing and adult rat brains

Nicastrin and presenilin 1 are integral components of the high molecular weight γ-secretase complexes that regulate proteolytic processing of various type I membrane proteins including amyloid precursor protein and Notch. At present, there is little information regarding the cellular distribution of nicastrin in the developing or adult rat brain. We report here, using immunoblotting and immunohistochemical methods, that nicastrin in the adult rat brain is widely expressed and co-localized with presenilin 1 in select neuronal populations within all major areas, including the basal forebrain, striatum, cortex, hippocampus, amygdala, thalamus, hypothalamus, cerebellum and brainstem. We also observed dense neuropil labeling in many regions in the brain, suggesting that nicastrin gets transported to dendrites and/or axon terminals in the central nervous system. The levels of nicastrin are found to be relatively high at the early stages of postnatal development and then declined gradually to reach the adult profile. At the cellular level, nicastrin is localized predominantly in neuronal cell bodies at early postnatal stages, but is apparent both in cell bodies and dendrites/neuropil in all brain regions at the later stages. The regulation of nicastrin expression and localization during development and its distribution in a wide spectrum of neurons in the postnatal and adult rat brains provide an anatomical basis to suggest a multifunctional role for the γ-secretase complex in the developing and adult rat brains.

Hypothalamus region‐specific global gene expression profiling in early stages of central endocrine disruption in rat neonates injected with estradiol benzoate or flutamide

To identify genes linked to early stages of disruption of brain sexual differentiation, hypothalamic region-specific microarray analyses were performed using a microdissection technique with neonatal rats exposed to endocrine-acting drugs. To validate the methodology, the expression fidelity of microarrays was first examined with two-round amplified antisense RNAs (aRNAs) from methacarn-fixed paraffin-embedded tissue (PET) in comparison with expression in unfixed frozen tissue (UFT). Decline of expression fidelity when compared with the 1x-amplified aRNAs from UFTs was found as a result of the preferential amplification of the 3' side of mRNAs in the second round in vitro transcription. However, expression patterns for the 2x-amplified aRNAs were mostly identical between methacarn-fixed PET and UFT, suggesting no obvious influence of methacarn fixation and subsequent paraffin embedding on expression levels. Next, in the main experiment, neonatal rats at birth were treated subcutaneously either with estradiol benzoate (EB; 10 microg/pup) or flutamide (FA; 250 microg/pup), and medial preoptic area (MPOA)-specific microarray analysis was performed 24 h later using 2x-amplified aRNAs from methacarn-fixed PET. Numbers of genes showing constitutively high expression in the MPOA predominated in males, implying a link with male-type growth supported by perinatal testosterone. Around 60% of genes showing sex differences in expression demonstrated altered levels after EB treatment in females, suggesting an involvement of genes necessary for brain sexual differentiation. When compared with EB, FA affected a rather small number of genes, but fluctuation was mostly observed in females, as with EB. Moreover, many selected genes common to EB and FA showed down-regulation in females with both drugs, suggesting a common mechanism for endocrine center disruption in females, at least at early stages of post-natal development.