Developmental Brain Research最新文献

Deficits in social behavior are found in several neuro-psychiatric disorders with a presumed developmental origin. The aim of the present study is to determine if prenatal stress at a given day of gestation alters social behavior in adult offspring. Pregnant rats were exposed to an acute stress (presence of a cat) either at the 10th (S10), the 14th (S14) or the 19th (S19) gestational day. When adult, their offsprings were studied in anxiety, neophobic and social behaviors. The results showed that S10 and S19 rats were more anxious and less aggressive than control rats, while the anxious and aggressive behavior of S14 rats was similar to that of the control ones. It is suggested that day 14 of pregnancy is a hyposensitive period to stressful agents due to an important plasticity of the developing gross nervous structures.

The comparative study of anti- and pro-saccade task performance contributes to our functional understanding of the frontal lobes, their alterations in psychiatric or neurological populations, and their changes during the life span. In the present study, we apply regression analysis to model life span developmental effects on various pro- and anti-saccade task parameters, using data of a non-representative sample of 327 participants aged 9 to 88 years. Development up to the age of about 27 years was dominated by curvilinear rather than linear effects of age. Furthermore, the largest developmental differences were found for intra-subject variability measures and the anti-saccade task parameters. Ageing, by contrast, had the shape of a global linear decline of the investigated saccade functions, lacking the differential effects of age observed during development. While these results do support the assumption that frontal lobe functions can be distinguished from other functions by their strong and protracted development, they do not confirm the assumption of disproportionate deterioration of frontal lobe functions with ageing. We finally show that the regression models applied here to quantify life span developmental effects can also be used for individual predictions in applied research contexts or clinical practice.

Although organotypic hippocampal slice cultures (OHSCs) are used to study function within the hippocampus, the effect of maintenance in vitro upon protein expression is not fully understood. Therefore, we examined developmental changes in cultures prepared from P8 rats and maintained on porous membranes between medium and atmosphere. Between 7 and 28 days following explantation, altered hippocampal morphology could not be detected despite a significant decrease in both MAP-2c and a mid-range tau isoform by 21 DIV. During the same period, lower GFAP expression was observed, and GFAP labeling suggested a migration of astrocytes to the slice–atmosphere interface. In contrast, levels of the synaptic proteins synaptophysin and PSD-95 were significantly increased, but GAP-43 was not. The preservation of myelinated axons and synapses, along with glial and endothelial cells, was confirmed by ultrastructural analysis. Furthermore, intranuclear inclusion bodies, which are associated with normal aging in vivo, were detected in the CA1 pyramidal layer in cultures older than 14 DIV. When OHSCs were maintained for approximately 3, 4, and 10 weeks, a rise and then fall in the expression of synaptophysin and, especially, PSD-95 were found, and the biphasic trend paralleled by significant changes in Schaffer collateral-evoked excitatory post-synaptic potentials from CA1 neurons. Our data not only describe changes in cytoskeletal, synaptic, and nuclear proteins related to the maintenance of interface OHSCs, but also emphasize the potential of the model for the study of age-related phenomena within the hippocampus.

Caspase-3, an apoptotic executor, has been shown in recent years to mediate non-lethal events like cellular proliferation and differentiation, primarily in studies related to non-neural tissue. In central nervous system development, the role of active caspase-3 is still unclear. We provide the first evidence for a potential new role of active (cleaved) caspase-3 in promoting differentiation of Bergmann glia. This study was predicated on the hypothesis that active caspase-3 is important for the differentiation of glia. We addressed the hypothesis through the following specific aims: (1) to establish the expression of active caspase-3 in glia; (2) to determine the developmental phenotype of the active caspase-3-expressing glia; and (3) to confirm that active caspase-3 expression is not mediating an apoptotic event. Through a temporal investigation from postnatal day 8 to 21, we observed that Bergmann glia express active caspase-3 without compromising their survival. Potential apoptotic fate of active caspase-3-positive Bergmann glia were ruled out based on immunohistochemical exclusion of phosphatidylserine exposure (Annexin V), DNA fragmentation (TUNEL), and DNA compaction (TOPRO-3). More than 90% of the active caspase-3-positive cells lacked colabeling for one of the apoptotic markers. Correlative studies using a proliferation marker Ki67 and a differentiation marker brain lipid-binding protein suggest that the expression of active caspase-3 was mostly associated with differentiating rather than proliferating Bergmann glia at all ages. Thus, this study supports the hypothesis that active caspase-3 may be regulating both differentiation of Bergmann glia by allowing the cells to exit the cell cycle and their morphogenesis.

We report the identification and isolation of limbal fibroblast-like cells from adult corneo-limbal tissue possessing self-renewing capacity and multilineage differentiation potential. The cells form cell aggregates or clusters, which express molecular markers, specific for ectoderm, mesoderm and endoderm lineages in vitro. Further, these cells mature into a myriad of cell types including neurons, corneal cells, osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes and pancreatic islet cells. Despite originating from a non-embryonic source, they express ESC and other stem cell markers important for maintaining an undifferentiated state. This multipotential capability, relatively easy isolation and high rate of ex vivo proliferation capacity make these cells a promising therapeutic tool.

It has been suggested that developmental alcohol-induced brain damage is mediated through increases in oxidative stress. In this study, the concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) were measured to indicate alcohol-mediated oxidative stress. In addition, the ability of two known antioxidants, melatonin (MEL) and lazaroid U-83836E (U), to attenuate alcohol-induced oxidative stress was investigated. Sprague–Dawley rat pups were randomly assigned to six artificially-reared groups, ALC (alcohol), MEL, MEL/ALC, U, U/ALC, and GC (gastrostomy control), and one normal suckle control (to control for artificial-rearing effects on the dependent variables). The daily dosages for ALC, MEL, and U were 6 g/kg, 20 mg/kg, and 20 mg/kg, respectively. Alcohol was administered in 2 consecutive feedings, and antioxidant (MEL or U) was administered for a total of 4 consecutive feedings (2 feedings prior to and 2 feedings concurrently with alcohol). The animals received treatment from postnatal days (PD) 4 through 9. Cerebellar, hippocampal, and cortical samples were collected on PD 9 and analyzed for MDA and GSH content. The results indicated that MDA concentrations in the cerebellum were significantly elevated in animals receiving alcohol; however, MDA levels in the hippocampus and cortex were not affected by alcohol treatment. Additionally, GSH levels in the cerebellum were significantly elevated in groups receiving alcohol, regardless of antioxidant treatment. Neither antioxidant was able to protect against alcohol-induced alterations of MDA or GSH. These findings suggest that alcohol might increase GSH levels indirectly as a compensatory mechanism designed to protect the brain from oxidative-stress-mediated insult.

The transcriptional regulator Pax6 is expressed in cerebellar granule cells and a mutation in that gene (Sey) has been shown to affect cerebellar development. We have defined novel phenotypes in the Sey/Sey cerebellum, indicating that the mutation of Pax6 alters granule cell behavior in vitro and also the interaction between granule cells and Purkinje cells in vivo. In culture, Sey/Sey granule cell precursors show the following abnormal phenotypes: enhanced proliferation, increased apoptotic cell death, and decreased number of morphologically differentiating β-III tubulin-positive cells. There is an overlap in the populations of Sey/Sey cells that express markers for proliferation and neuronal differentiation indicating an abnormality in the transition between these states in granule cells. In vivo, Purkinje cell ectopias were found deep in the cerebellum and extending into the inferior colliculus. Coincident with this, Purkinje cell phenotype was the alteration in the pattern and levels of Reelin expression in granule cells of the external germinal layer (EGL). The finding of increased staining for Disabled-1, a signaling pathway intermediary that is normally downregulated by a Reelin signal, throughout the Purkinje cell population suggests that in the Sey/Sey cerebellum there is a disruption in Reelin signaling from the EGL to Purkinje cells. These findings suggest that Pax6 is critical for the proper differentiation of granule cells and their communication with developing Purkinje cells. Thus, through its guidance of granule cell development, Pax6 also has a strong influence on many of the cellular programs that guide the morphogenesis of the entire cerebellum.