Browsing by Author "Pinto, Luísa"
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- Glial-restricted precursors stimulate endogenous cytogenesis and effectively recover emotional deficits in a model of cytogenesis ablationPublication . Martins-Macedo, Joana; Araújo, Bruna; Anjo, Sandra I.; Silveira-Rosa, Tiago; Patrício, Patrícia; Alves, Nuno Dinis; Silva, Joana M.; Teixeira, Fábio G.; Manadas, Bruno; Rodrigues, Ana J.; Lepore, Angelo C.; Salgado, António J.; Gomes, Eduardo D.; Pinto, Luísa; Gomes, EduardoAdult cytogenesis, the continuous generation of newly-born neurons (neurogenesis) and glial cells (gliogenesis) throughout life, is highly impaired in several neuropsychiatric disorders, such as Major Depressive Disorder (MDD), impacting negatively on cognitive and emotional domains. Despite playing a critical role in brain homeostasis, the importance of gliogenesis has been overlooked, both in healthy and diseased states. To examine the role of newly formed glia, we transplanted Glial Restricted Precursors (GRPs) into the adult hippocampal dentate gyrus (DG), or injected their secreted factors (secretome), into a previously validated transgenic GFAP-tk rat line, in which cytogenesis is transiently compromised. We explored the long-term effects of both treatments on physiological and behavioral outcomes. Grafted GRPs reversed anxiety-like deficits and demonstrated an antidepressant-like effect, while the secretome promoted recovery of only anxiety-like behavior. Furthermore, GRPs elicited a recovery of neurogenic and gliogenic levels in the ventral DG, highlighting the unique involvement of these cells in the regulation of brain cytogenesis. Both GRPs and their secretome induced significant alterations in the DG proteome, directly influencing proteins and pathways related to cytogenesis, regulation of neural plasticity and neuronal development. With this work, we demonstrate a valuable and specific contribution of glial progenitors to normalizing gliogenic levels, rescuing neurogenesis and, importantly, promoting recovery of emotional deficits characteristic of disorders such as MDD.
- StressMatic: Bridging innovation and reliability in animal models of stressPublication . Martins-Macedo, Joana; Gomes, Eduardo D.; Oliveira, João F.; Patrício, Patrícia; Pinto, Luísa; Gomes, EduardoPreclinical research involving animal models of stress exposure typically rely on traditional manual protocols, which are laborious and time-consuming and may compromise reproducibility and the effective translation of f indings into clinical applications. StressMatic is an automated stress exposure system (auCMS), designed to improve the standardization and reproducibility of stress-induction methodologies. The auCMS demonstrated consistent efficacy, with animals subjected to automated stressors displaying similar responses to those exposed to conventional manual methods, thus confirming its validity as a reliable tool. While some stressors still require human involvement, the automation of key processes has markedly enhanced efficiency and minimized operational time. This innovative approach reduces the introduction of human error, increases precision, and standardizes experimental workflows, resulting in a more robust preclinical research platform. By streamlining repetitive tasks, the auCMS promotes adaptability in experimental design, particularly in the study of mood disorders. Ultimately, this automated protocol not only enhances the reliability of pharmaceutical screening processes but also strengthens the drug discovery pipeline, facilitating deeper insights into behavioral outcomes and informing therapeutic strategies.