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Influence of BDNF and FCS on viability and programmed cell death (PCD) of developing cortical chicken neurons in vitro.

Programmed cell death (PCD) has been proposed to occur in vitro after withdrawal of growth factors and serum deprivation. In the present study the influence of brain derived neurotrophic factor (BDNF) and different serum (FCS) concentrations on viability, survival and apoptotic cell death of cortical cells from 8 days old chicken embryos after 3, 5 or 7 DIV was investigated. Results show that BDNF as well as fetal calf serum (FCS) influence the metabolism of neurons. Furthermore, serum, but not BDNF, is able to protect neurons from cell death. For the detection of apoptosis TUNEL-staining and DNA gel electrophoresis was performed. These methods supplied contrary information about the type of cell death in neurons raised without serum. The first technique indicates the occurrence of apoptosis whereas the second suggests necrosis. In addition, by the means of DNA gel electrophoresis it was exhibited that cortical cells from 8 days old chicken embryos are committed to undergo PCD already in vivo at time of preparation.

Animals↗

Characterization of a cDNA encoding a proline-rich 14 kDa protein in developing cortical cells of the roots of bean (Phaseolus vulgaris) seedlings.

A cDNA clone, corresponding to mRNAs preferentially expressed in the roots of bean (Phaseolus vulgaris L.) seedlings, was isolated. This clone contains a 381 bp open reading frame encoding a polypeptide of 13.5 kDa, designated PVR5 (Phaseolus vulgaris root 5). The amino acid sequence of this clone is rich in proline (13.5%) and leucine (12.7%) and shares significant amino acid sequence homology with root-specific and proline-rich proteins from monocots (maize and rice), and proline-rich proteins from dicots (carrot, oilseed rape, and Madagascar periwinkle). The precise biological roles of these polypeptides are unknown. PVR5 mRNA accumulation is developmentally regulated within the root, with high levels at the root apex and declining levels at distances further from the root tip. In situ hybridization shows that PVR5 mRNA specifically accumulates in the cortical ground meristem in which maximal cell division occurs. Southern blot analysis suggests that genomic DNA corresponding to PVR5 cDNA is encoded by a single gene or a small gene family.

Amino Acid Sequence↗

An mRNA that specifically accumulates in maize roots delineates a novel subset of developing cortical cells.

A near full-length cDNA clone (pZRP3) corresponding to an mRNA that accumulates specifically in roots of maize was isolated. The ZRP3 mRNA is ca. 600 nucleotides in length. The amino acid sequence of the predicted polypeptide is rich in leucine (16%), proline (11%), and cysteine (8.5%). The zrp3 gene appears to be expressed exclusively in roots, whereas other ZRP3-related genes are expressed in additional organs of the maize plant. In situ hybridization shows that ZRP3 mRNA accumulation is largely confined to the cells of the cortical ground meristem. Furthermore, accumulation of this mRNA occurs within a distinct subset of cortical cells, the inner three to four cell layers.

Amino Acid Sequence↗

Differential immunocytochemical staining for fetuin and transferrin in the developing cortical plate.

The distribution of the plasma proteins fetuin and transferrin in fetal sheep neocortex has been studied using the indirect immunoperoxidase method. Most of the cells (presumed to be neurons) in the early cortical plate (35 days gestation) were positive for fetuin. In contrast the fibre systems on either side of the cortical plate were positive for transferrin; some fibres were weakly positive for fetuin. It is proposed that these fibres may originate from brainstem and perhaps from some thalamic nuclei and that the plasma proteins are probably transferred from the neuronal cell bodies to their peripheral processes. It is further suggested that plasma proteins such as fetuin and transferrin may have a role in neuronal differentiation and synaptogenesis.

Animals↗

Cross-modal plasticity in cortical development: differentiation and specification of sensory neocortex.

Early developmental manipulations can induce sensory afferents of one modality to project to central targets of a different sensory modality. We and other investigators have used such cross-modal plasticity to examine the role of afferent inputs and their patterns of activity in the development of sensory neocortex. We suggest that the afferent rewiring can significantly influence the internal connectivity or microcircuitry of sensory cortex, aspects of which appear to be determined or specified relatively late in development, but that they cannot influence, or influence only to a minor extent, the laminar characteristics and external connectivity patterns of cortex, which appear to be specified earlier.

Animals↗

Disrupted cerebellar cortical development and progressive degeneration of Purkinje cells in SV40 T antigen transgenic mice.

SV40 T antigen (Tag) expression directed to cerebellar Purkinje cells resulted in the generation of three transgenic mouse lines that displayed ataxia, a neurological phenotype characteristic of cerebellar dysfunction. Onset of symptoms and cerebellar pathology, characterized by specific Purkinje cell degeneration, appeared to be directly dependent upon transgene copy number. The SV5 line (containing > 30 transgene copies), exhibited embryonic transgene expression that caused selective death of immature Purkinje cells and a subsequent block in cerebellar development and ataxia at 2 weeks. The developmental effect of the disruption of Purkinje cells in SV5 mice suggests that a normal complement of these cells is required for early development of the cerebellar cortex, especially granule cell proliferation and migration from external to internal layers. Transgene expression in a second line, SV4 (10 copies), was detectable during the second postnatal week. Death of mature Purkinje cells in the SV4 line resulted in onset of ataxia at 9 weeks. Ataxia in a third line, SV6 (2 copies), was detected after 15 weeks. The distinct cerebellar phenotypes of the SV4-6 lines correlate with specific Tag-induced Purkinje cell ablation as opposed to tumorigenesis.

Animals↗

Coordinate activity in retinal and cortical development.

New approaches for detecting and manipulating patterns of neuronal activity have revealed diverse strategies for constructing circuits in the developing brain. Spontaneously generated patterns can provide activity-based information before the onset of sensory inputs. In addition to mechanisms based on chemical synaptic communication, coordination of activity via gap junctions can provide important cues for synchronous activity early in circuit formation.

Animals↗

Is acne really a disease?: a theory of acne as an evolutionarily significant, high-order psychoneuroimmune interaction timed to cortical development with a crucial role in mate choice.

Adolescent acne is considered from the perspective of evolutionary psychology with an emphasis on a role in mate choice. The fact that acne, which is almost universal and not a true infection, is (1) initiated at puberty by the action of pubertal hormones on likely distinct, pro-acne follices, and (2) typically resolves in one's early twenties when prefrontal cortex development is complete, suggests that the condition's timeframe is meaningful. Acne's conspicuous localization on the face, and its ability to elicit reflexive disgust and avoidance in observers, suggests a possible role in sexual selection. The pathophysiology of acne is reviewed, and the suggestion made that, far from being a disease, adolescent acne is a normal physiological process - a high-order psychoneuroimmune interaction - that functions to ward off potential mates until the afflicted individual is some years past the age of reproductive maturity, and thus emotionally, intellectually, and physically fit to be a parent.

Acne Vulgaris↗

Determinants of drug brain uptake in a rat model of seizure-associated malformations of cortical development.

We examined the blood-brain barrier (BBB) function in methylazoxymethanol acetate (MAM)-treated rats, a model of human developmental brain malformations. We found aberrant vessels morphology and serum albumin leakage in the heterotopic (malformed) hippocampus; these changes were associated with a significant increase in endothelial P-glycoprotein (P-gp) expression. Seizures exacerbated BBB leakage and greatly augmented P-gp expression in vessels and additionally in perivascular/parenchymal astrocytes. The effects of seizures were observed to a much larger extent in malformed than in normal brain tissue. The intrinsic changes in BBB function in MAM-exposed rats were associated with increased blood-to-brain penetration of ondansetron, a P-gp substrate. However, a marked reduction in drug brain levels was provoked by seizures, and this effect was reversed by selective blockade of P-gp activity with tariquidar. Changes in BBB function may critically contribute to determine the brain uptake and distribution of P-gp substrates in epileptic tissue associated with developmental malformations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗