ABSTRACT
BACKGROUND: Mutations in the X-linked gene cyclin-dependent kinase-like 5 (CDKL5) cause a severe neurological disorder characterised by early-onset epileptic seizures, autism and intellectual disability (ID). Impaired hippocampal function has been implicated in other models of monogenic forms of autism spectrum disorders and ID and is often linked to epilepsy and behavioural abnormalities. Many individuals with CDKL5 deficiency disorder (CDD) have null mutations and complete loss of CDKL5 protein, therefore in the current study we used a Cdkl5-/y rat model to elucidate the impact of CDKL5 loss on cellular excitability and synaptic function of CA1 pyramidal cells (PCs). We hypothesised abnormal pre and/or post synaptic function and plasticity would be observed in the hippocampus of Cdkl5-/y rats. METHODS: To allow cross-species comparisons of phenotypes associated with the loss of CDKL5, we generated a loss of function mutation in exon 8 of the rat Cdkl5 gene and assessed the impact of the loss of CDLK5 using a combination of extracellular and whole-cell electrophysiological recordings, biochemistry, and histology. RESULTS: Our results indicate that CA1 hippocampal long-term potentiation (LTP) is enhanced in slices prepared from juvenile, but not adult, Cdkl5-/y rats. Enhanced LTP does not result from changes in NMDA receptor function or subunit expression as these remain unaltered throughout development. Furthermore, Ca2+ permeable AMPA receptor mediated currents are unchanged in Cdkl5-/y rats. We observe reduced mEPSC frequency accompanied by increased spine density in basal dendrites of CA1 PCs, however we find no evidence supporting an increase in silent synapses when assessed using a minimal stimulation protocol in slices. Additionally, we found no change in paired-pulse ratio, consistent with normal release probability at Schaffer collateral to CA1 PC synapses. CONCLUSIONS: Our data indicate a role for CDKL5 in hippocampal synaptic function and raise the possibility that altered intracellular signalling rather than synaptic deficits contribute to the altered plasticity. LIMITATIONS: This study has focussed on the electrophysiological and anatomical properties of hippocampal CA1 PCs across early postnatal development. Studies involving other brain regions, older animals and behavioural phenotypes associated with the loss of CDKL5 are needed to understand the pathophysiology of CDD.
Subject(s)
Disease Models, Animal , Long-Term Potentiation , Protein Serine-Threonine Kinases , Receptors, AMPA , Receptors, N-Methyl-D-Aspartate , Spasms, Infantile , Animals , Male , Rats , CA1 Region, Hippocampal/metabolism , CA1 Region, Hippocampal/pathology , CA1 Region, Hippocampal/physiopathology , Epileptic Syndromes/genetics , Epileptic Syndromes/metabolism , Excitatory Postsynaptic Potentials , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/metabolism , Genetic Diseases, X-Linked/physiopathology , Hippocampus/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Pyramidal Cells/metabolism , Pyramidal Cells/pathology , Receptors, AMPA/metabolism , Receptors, AMPA/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Receptors, N-Methyl-D-Aspartate/genetics , Spasms, Infantile/genetics , Spasms, Infantile/metabolism , Synapses/metabolismABSTRACT
Objetivo: identificar quais os estilos de liderança utilizados por enfermeiros gestores e compreender a sua influência no burnoutdos enfermeiros no contexto de trabalho.Método: scoping review, realizada em abril de 2021, conduzida de acordo com a metodologia de Joanna Briggs Institute. Dois revisores independentes avaliaram a relevância dos artigos, a extração e síntese dos dados. Resultados: foram identificados 3.532 estudos na pesquisa bibliográfica, dos quais sete estudos apresentaram as características de elegibilidade para a inclusão na revisão. Os estilos de liderança identificados na literatura foram a liderança transformacional e liderança autêntica que revelam um impacto positivo na redução do burnout; a liderança laissez-faire que, pelo contrário, promove um ambiente facilitador do desenvolvimento da síndrome em estudo; a liderança transacional, por sua vez, não demonstrou resultados significativos na diminuição e prevenção de burnout, assim como, a liderança autocrática, carismática e situacional cujos resultados não se demonstraram quantificáveis para a sua prevenção. Conclusão: o estilo de liderança transformacional foi aquele que maior relevância demonstrou tanto na prevenção como diminuição do desenvolvimento de burnoutnos enfermeiros.
Objective: identify which leadership styles are used by nurse managers and understand their influence on nurse's burnout nurses in the work context. Method: scoping review, carried out in April 2021, conducted according to the Joanna Briggs Institute methodology. Two independent reviewers assessed the relevance of the articles, the extraction and synthesis of data. Results: 3.532 studies were identified in the literature search, of which seven studies presented the eligibility characteristics for inclusion in the review.The leadership styles identified in the literature were transformational leadership and authentic leadership that reveal a positive impact on reducing burnout; laissez-faire leadership that, on the contrary, promotes an environment that facilitates the development of the syndrome under study; transactional leadership, in turn, did not show significant results in reducing and preventing burnout, as well as autocratic, charismatic and situational leadership whose results were not quantifiable for its prevention.Conclusion: it was concluded that the transformational leadership style was the one that showed the greatest relevance both in preventing and reducing the development of burnoutin nurses.
Objetivo: identificar qué estilos de liderazgo son utilizados por las enfermeras gestoras y comprender su influencia en el agotamiento de las enfermeras en el contexto de trabajo.Método: scoping review, realizado en abril de 2021, según la metodología Joanna Briggs Institute. Dos revisores independientes evaluaron la relevancia de los artículos, la extracción y síntesis de datos. Resultados: se identificaron 3.532 estudios en la búsqueda bibliográfica, de los cuales siete estudios presentaron las características de elegibilidad para su inclusión en la revisión. Los estilos de liderazgo identificados en la literatura fueron el liderazgo transformacional y el liderazgo auténtico que revelan un impacto positivo en la reducción del burnout; liderazgo laissez-faire que, por el contrario, promueve un entorno que facilita el desarrollo del síndrome en estudio; el liderazgo transaccional, por su parte, no mostró resultados significativos enla reducción y prevención del burnout, así como el liderazgo autocrático, carismático y situacional cuyos resultados no fueron cuantificables para su prevención. Conclusión: se concluyó que el estilo de liderazgo transformacional fue el que mostró mayor relevancia tanto en la prevención como en la reducción del desarrollo del burnout en enfermeros.