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1.
Int J Dev Neurosci ; 82(3): 277-285, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35212007

RESUMO

Alterations in the generation, migration and integration of different subtypes of neurons in the medial prefrontal cortex (mPFC) microcircuit could play an important role in vulnerability to schizophrenia. Using in vivo cell-type specific manipulation of pyramidal neurons (PNs) progenitors, we aim to investigate the role of the schizophrenia risk-gene DiGeorge Critical Region 2 (Dgcr2) on cortical circuit formation in the mPFC of developing mice. This report describes how Dgcr2 knock down in upper-layer PNs impacts the functional maturation of PNs and interneurons (INs) in the mPFC. First, we demonstrate that Dgcr2 knock-down disrupts laminar positioning, dendritic morphology and excitatory activity of upper-layer PNs. Interestingly, inhibitory activity is also modified in Dgcr2 knock-down PNs, suggesting a broader microcircuit alteration involving interneurons. Further analyses show that the histological maturation of parvalbumin (PV) INs is not dramatically impaired, thus implying that other INs subtypes might be at play in the reported microcircuit alteration. Overall, this study unravels how local functional deficits of the early postnatal development of the mPFC can be induced by Dgcr2 knock-down in PNs.


Assuntos
Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Esquizofrenia , Animais , Regulação para Baixo , Interneurônios/metabolismo , Camundongos , Parvalbuminas/genética , Parvalbuminas/metabolismo , Córtex Pré-Frontal , Esquizofrenia/genética
2.
Sci Rep ; 7(1): 4406, 2017 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-28667331

RESUMO

Recently it was suggested that the phylogenetic clustering of Mesozoic marine reptile lineages, such as thalattosaurs, the very successful fish-shaped ichthyosaurs and sauropterygians (including plesiosaurs), among others, in a so-called 'superclade' is an artefact linked to convergent evolution of morphological characters associated with a shared marine lifestyle. Accordingly, partial 'un-scoring' of the problematic phylogenetic characters was proposed. Here we report a new, exceptionally preserved and mostly articulated juvenile skeleton of the diapsid reptile, Eusaurosphargis dalsassoi, a species previously recovered within the marine reptile 'superclade', for which we now provide a revised diagnosis. Using micro-computed tomography, we show that besides having a deep skull with a short and broad rostrum, the most outstanding feature of the new specimen is extensive, complex body armour, mostly preserved in situ, along its vertebrae, ribs, and forelimbs, as well as a row of flat, keeled ventrolateral osteoderms associated with the gastralia. As a whole, the anatomical features support an essentially terrestrial lifestyle of the animal. A review of the proposed partial character 'un-scoring' using three published data matrices indicate that this approach is flawed and should be avoided, and that within the marine reptile 'superclade' E. dalsassoi potentially is the sister taxon of Sauropterygia.


Assuntos
Fósseis , Filogenia , Répteis/classificação , Répteis/genética , Animais , Evolução Biológica , Répteis/anatomia & histologia
3.
Anesthesiology ; 126(5): 855-867, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28301408

RESUMO

BACKGROUND: General anesthetics potentiating γ-aminobutyric acid (GABA)-mediated signaling are known to induce a persistent decrement in excitatory synapse number in the cerebral cortex when applied during early postnatal development, while an opposite action is produced at later stages. Here, the authors test the hypothesis that the effect of general anesthetics on synaptogenesis depends upon the efficacy of GABA receptor type A (GABAA)-mediated inhibition controlled by the developmental up-regulation of the potassium-chloride (K-Cl) cotransporter 2 (KCC2). METHODS: In utero electroporation of KCC2 was used to prematurely increase the efficacy of (GABAA)-mediated inhibition in layer 2/3 pyramidal neurons in the immature rat somatosensory cortex. Parallel experiments with expression of the inward-rectifier potassium channel Kir2.1 were done to reduce intrinsic neuronal excitability. The effects of these genetic manipulations (n = 3 to 4 animals per experimental group) were evaluated using iontophoretic injection of Lucifer Yellow (n = 8 to 12 cells per animal). The total number of spines analyzed per group ranged between 907 and 3,371. RESULTS: The authors found a robust effect of the developmental up-regulation of KCC2-mediated Cl transport on the age-dependent action of propofol on dendritic spines. Premature expression of KCC2, unlike expression of a transport-inactive KCC2 variant, prevented a propofol-induced decrease in spine density. In line with a reduction in neuronal excitability, the above result was qualitatively replicated by overexpression of Kir2.1. CONCLUSIONS: The KCC2-dependent developmental increase in the efficacy of GABAA-mediated inhibition is a major determinant of the age-dependent actions of propofol on dendritic spinogenesis.


Assuntos
Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/metabolismo , Propofol/farmacologia , Simportadores/efeitos dos fármacos , Simportadores/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Eletroporação , Feminino , Hipnóticos e Sedativos/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Ratos , Ratos Wistar , Receptores de GABA/efeitos dos fármacos , Córtex Somatossensorial/efeitos dos fármacos , Córtex Somatossensorial/embriologia , Córtex Somatossensorial/metabolismo , Cotransportadores de K e Cl-
4.
Toxicol Sci ; 149(1): 121-33, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26424773

RESUMO

The possibility that exposure to general anesthetics during early life results in long-term impairment of neural function attracted considerable interest over the past decade. Extensive laboratory data suggest that administration of these drugs during critical stages of central nervous system development can lead to cell death, impaired neurogenesis, and synaptic growth as well as cognitive deficits. These observations are corroborated by several recent human epidemiological studies arguing that such cognitive impairment might also occur in humans. Despite the potential public health importance of this issue, several important questions remain open. Amongst them, how the duration of anesthesia exposure impact on outcome is as yet not fully elucidated. To gain insight into this question, here we focused on the short- and long-term impact of a 30-min-long exposure to clinically relevant concentrations of sevoflurane in rat pups at 2 functionally distinct stages of the brain growth spurt. We show that this treatment paradigm induced developmental stage-dependent and brain region-specific acute but not lasting changes in dendritic spine densities. Electrophysiological recordings in hippocampal brain slices from adult animals exposed to anesthesia in the early postnatal period revealed larger paired-pulse facilitation but no changes in the long-term potentiation paradigm when compared with nonanesthetized controls. 5-bromo-2-deoxyuridine pulse and pulse-chase experiments demonstrated that neither proliferation nor differentiation and survival of hippocampal progenitors were affected by sevoflurane exposure. In addition, behavioral testing of short- and long-term memory showed no differences between control and sevoflurane-exposed animals. Overall, these results suggest that brief sevoflurane exposure during critical periods of early postnatal development, although it does not seem to exert major long-term effects on brain circuitry development, can induce subtle changes in synaptic plasticity and spine density of which the physiological significance remains to be determined.


Assuntos
Anestésicos Inalatórios/toxicidade , Espinhas Dendríticas/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Éteres Metílicos/toxicidade , Plasticidade Neuronal/efeitos dos fármacos , Anestesia , Animais , Animais Recém-Nascidos , Hipocampo/patologia , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Sevoflurano
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