Percorrer por autor "Gomes, Eduardo D."
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- Focused Neuroprotection in Parkinson's Disease: Effects of N-Acetylcysteine and MRI-guided Ultrasound NeuromodulationPublication . Silva, Rita Caridade; Araújo, B.; Vilaça-Ferreira, A. C.; Vilela, C.; Teixeira, C.; Martins-Macedo, J.; Soares-Guedes, C.; Gomes, Eduardo D.; Meriaux, S.; Larrat, B.; Wade-Martins, R.; Fernandes, H. J.; Teixeira, F.; Gomes, EduardoParkinson’s Disease (PD) is characterized by a progressive degeneration of dopaminergic neurons (DAn) in the brain, leading to severe symptomatology. Current treatments mainly address motor symptoms rather than preventing DAn damage or degeneration. Hence, there is an urgent need for novel strategies, particularly those that can combine neuroprotective and neuroregenerative approaches [1]. Drug repurposing is a powerful method for identifying new applications for approved drugs outside the scope of the original medical indication [2]. Under this concept, N-acetylcysteine (NAC), a potent antioxidant, has shown therapeutic abilities in modulating oxidative stress and preventing dopamine-induced cell death [3], suggesting potential disease-modifying actions in PD. Notably, recent data from our team revealed that NAC could restore dopamine transporter (DAT) levels in the dorsal striatum of PD animals [4].
- 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.
- Neuroinflammation and Parkinson’s disease—from neurodegeneration to therapeutic opportunitiesPublication . Araújo, Bruna; Caridade-Silva, Rita; Soares-Guedes, Carla; Martins-Macedo, Joana; Gomes, Eduardo D.; Monteiro, Susana; Teixeira, Fábio G.Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder world wide. Clinically, it is characterized by a progressive degeneration of dopaminergic neurons (DAn), resulting in severe motor complications. Preclinical and clinical studies have indicated that neuroin flammation can play a role in PD pathophysiology, being associated with its onset and progression. Nevertheless, several key points concerning the neuroinflammatory process in PD remain to be answered. Bearing this in mind, in the present review, we cover the impact of neuroinflammation on PD by exploring the role of inflammatory cells (i.e., microglia and astrocytes) and the interconnections between the brain and the peripheral system. Furthermore, we discuss both the innate and adaptive immune responses regarding PD pathology and explore the gut–brain axis communication and its influence on the progression of the disease.
- 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.