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Radial glia are transiently present in the developing cerebral cortex, where they are thought to guide the migration of neurons from the proliferative zone to the forming cortical plate. To provide a framework for experimental studies of radial glia, we have defined morphological and immunocytochemical criteria to identify them in primary cultures of cortical cells obtained at embryonic day 13 in the mouse. Cortical radial glia in culture for 1-2 d resemble radial glia in vivo: they have a long, thin, unbranched process extending from one or both ends of the elongated cell body and are labeled with the monoclonal antibody RC1 but not with antibodies to glial fibrillary acidic protein (abGFAP). We tested the specificity of RC1 by double-labeling with a panel of cell-type specific antibodies, and found that it labels radial glia, astrocytes, and fibroblast-like cells, but not neurons. Fibroblasts are easily distinguished from glia by morphology and by labeling with antibodies to fibronectin. To test the hypothesis that radial glia become astrocytes when their developmental role is complete, we examined their morphological and immunocytochemical development in culture. After 3-4 d in vitro radial glia develop several branched processes; in this transitional stage they are labeled by both RC1 and abGFAP. Many radial glia lose RC1 immunoreactivity as they become increasingly branched and immunoreactive to abGFAP. In areas of the cultures that have few neurons and in cultures depleted of neurons by washing, flat, nonprocess-bearing glia predominate. These cells do not lose immunoreactivity to RC1 during the 9-d period of observation even though they acquire GFAP.(ABSTRACT TRUNCATED AT 250 WORDS)

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Creativity has been proposed to be either the result of solely right hemisphere processes or of interhemispheric interactions. Little information is available, however, concerning the neuronal foundations of creativity. In this study, we introduced a new artistic task, designing a new tool (a pen), which let us quantitatively evaluate creativity by three indices of originality. These scores were analyzed in combination with brain activities measured by functional magnetic resonance imaging (fMRI). The results were compared between subjects who had been formally trained in design (experts) and novice subjects. In the experts, creativity was quantitatively correlated with the degree of dominance of the right prefrontal cortex over that of the left, but not with that of the right or left prefrontal cortex alone. In contrast, in novice subjects, only a negative correlation with creativity was observed in the bilateral inferior parietal cortex. We introduced structure equation modeling to analyze the interactions among these four brain areas and originality indices. The results predicted that training exerts a direct effect on the left parietal cortex. Additionally, as a result of the indirect effects, the activity of the right prefrontal cortex was facilitated, and the left prefrontal and right parietal cortices were suppressed. Our results supported the hypothesis that training increases creativity via reorganized intercortical interactions.

A monoclonal antibody, 4D7, obtained with embryonic rat brain as an immunogen, recognizes an epitope on 3 protein species of 150-160,100-110, and 80 kDa, present in mouse and rat brain during the fetal period. Vital immunostaining of dissociated cultures of fetal forebrain indicates that the antigen is localized largely on the external plasma membrane of a subpopulation of neurites. Immunocytochemistry reveals that the distribution of the antigen in viva is restricted to the nervous system. Immunoreactivity is concentrated primarily in the pathways of a limited set of CNS and PNS axon systems during early stages of their development, as delineated by staining with the neurofilament antibody, C2. Depending on the particular axon system, immunoreactivity with 4D7 persists only for one to several days of prenatal or perinatal development. In the spinal cord, stage-specific-neurite-associated proteins (SNAP) expression occurs first along motor axon pathways on embryonic day (E) 10 and then within the nerve trunks of dorsal root ganglia and the commissural fiber system on Ell. Immunoreactivity is detectable among most cranial nerves starting in the interval from El1 to E13. Within the brain, the onset of SNAP expression within several discrete axon tracts occurs in the interval E14-16, including the lateral olfactory tract, anterior commissure, corpus callosum, fasciculus retroflexus, and fornix. Immunoreactivity within the embryonic intermediate zones of some structures matches the location of certain other axon systems. Sites of 4D7 staining which do not correspond to the location of axon populations include the internal portion of the external granular layer of the postnatal cerebellum and the cortex of the reeler mutant mouse. The predominant localization of the 4D7 antigen among axon systems and its precisely regulated spatiotemporal pattern of expression are consistent with the possibility that the SNAP antigens play a significant role in the early stages of growth of axonal tracts in viva.In the last decade, intensive research efforts have been directed towards finding molecules that are involved in regulating axonal growth. One major approach has been to look for substances present in conditioned media of cultured cells or in tissue extracts that promote neurite outgrowth from dissociated or explanted neuronal cells in vitro. In addition to NGF, a number of protein species responsible for such effects are currently under

Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.

Thioredoxin 1 (Trx1) has redox-sensitive cysteine residues and acts as an antioxidant in cells. However, the extent of Trx1 contribution to overall antioxidant mechanisms is unknown in any organs. We generated transgenic mice with cardiac-specific overexpression of a dominant negative (DN) mutant (C32S/C35S) of Trx1 (Tg-DN-Trx1 mice), in which the activity of endogenous Trx was diminished. Markers of oxidative stress were significantly increased in hearts from Tg-DN-Trx1 mice compared with those from nontransgenic (NTg) mice. Tg-DN-Trx1 mice exhibited cardiac hypertrophy with maintained cardiac function at baseline. Intraperitoneal injection of N-2-mercaptopropionyl glycine, an antioxidant, normalized cardiac hypertrophy in Tg-DN-Trx1 mice. Thoracic aortic banding caused greater increases in myocardial oxidative stress and enhanced hypertrophy in Tg-DN-Trx1 compared with NTg mice. In contrast, transgenic mice with cardiac-specific overexpression of wild-type Trx1 did not show cardiac hypertrophy at baseline but exhibited reduced levels of hypertrophy and oxidative stress in response to pressure overload. These results demonstrate that endogenous Trx1 is an essential component of the cellular antioxidant mechanisms and plays a critical role in regulating oxidative stress in the heart in vivo. Furthermore, inhibition of endogenous Trx1 in the heart primarily stimulates hypertrophy, both under basal conditions and in response to pressure overload through redox-sensitive mechanisms.