9 research outputs found

    Prenatal stress and subsequent exposure to chronic mild stress influence dendritic spine density and morphology in the rat medial prefrontal cortex

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    <p>Abstract</p> <p>Background</p> <p>Both prenatal stress (PS) and postnatal chronic mild stress (CMS) are associated with behavioral and mood disturbances in humans and rodents. The aim of this study was to reveal putative PS- and/or CMS-related changes in basal spine morphology and density of pyramidal neurons in the rat medial prefrontal cortex (mPFC).</p> <p>Results</p> <p>We show that rats exposed to PS and/or CMS display changes in the morphology and number of basal spines on pyramidal neurons in the mPFC. CMS had a negative effect on spine densities, particularly on spines of the mushroom type, which are considered to form stronger and more stable synapses than other spine types. PS alone did not affect spine densities, but had a negative effect on the ratio of mushroom spines. In addition, PS seemed to make rats less responsive to some of the negative effects of CMS, which supports the notion that PS represents a predictive adaptive response.</p> <p>Conclusion</p> <p>The observed changes may represent a morphological basis of PS- and CMS-related disturbances, and future studies in the field should not only consider total spine densities, but also separate between different spine types.</p

    Area-specific reestablishment of damaged circuits in the adult cerebral cortex by cortical neurons derived from mouse embryonic stem cells

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    Pluripotent stem-cell-derived neurons constitute an attractive source for replacement therapies, but their utility remains unclear for cortical diseases. Here, we show that neurons of visual cortex identity, differentiated in vitro from mouse embryonic stem cells (ESCs), can be transplanted successfully following a lesion of the adult mouse visual cortex. Reestablishment of the damaged pathways included long-range and reciprocal axonal projections and synaptic connections with targets of the damaged cortex. Electrophysiological recordings revealed that some grafted neurons were functional and responsive to visual stimuli. No significant integration was observed following grafting of the same neurons in motor cortex, or transplantation of embryonic motor cortex in visual cortex, indicating that successful transplantation required a match in the areal identity of grafted and lesioned neurons. These findings demonstrate that transplantation of mouse ESC-derived neurons of appropriate cortical areal identity can contribute to the reconstruction of an adult damaged cortical circuit.publisher: Elsevier articletitle: Area-Specific Reestablishment of Damaged Circuits in the Adult Cerebral Cortex by Cortical Neurons Derived from Mouse Embryonic Stem Cells journaltitle: Neuron articlelink: http://dx.doi.org/10.1016/j.neuron.2015.02.001 content_type: article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe

    Pyramidal neurons derived from human pluripotent stem cells integrate efficiently into mouse brain circuits in vivo.

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    The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair. VIDEO ABSTRACT:Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe
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