Percorrer por autor "Martins-Macedo, Joana"
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- From peripheral to central (Neuro)degeneration: Is heart-kidney a new axial paradigm for Parkinson’s disease?Publication . Teixeira, Catarina; Caridade-Silva, Rita; Martins-Macedo, Joana; Araújo, Bruna; Gomes, Eduardo; Vilela, Cristiana; Soares-Guedes, Carla; Pires, Inês Falcão; Alencastre, Inês; G. Teixeira, Fábio; Gomes, EduardoParkinson’s Disease (PD) is primarily characterized by the accumulation of alpha-synuclein (αSyn) and the loss of dopaminergic neurons (DAn). The most evident repercussions of the disease include sympathetic and parasympathetic dysfunction, decreased dopamine (DA) levels, and impaired voluntary movements. Given the multifactorial nature of PD, it is now recognized that several systemic diseases may predispose individuals to the onset and progression of PD as well as influence its therapeutic outcomes. Recent studies have highlighted that patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) face an increased risk of developing PD, independent of the shared risk factors. Indeed, substantial evidence supports the connections between the brain, heart, and kidneys. Elements such as the dopaminergic system, blood pressure regulation, inflammation, autophagy, oxidative stress, and calcium (Ca2+) signaling are recognized as crucial for the functioning of each organ individually. However, these factors may also significantly impact the overall health of the triad. Understanding the interconnection between the brain, heart, and kidneys would be groundbreaking in enhancing our knowledge about their interactions, enabling prompt interventions in the early stages of the disease. With this perspective, this review analyzes the current understanding of the brain-heart-kidney axis as a potential new paradigm for diagnosing and managing PD.
- 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.
- N-Acetylcysteine treatment may compensate motor impairments through dopaminergic transmission modulation in a striatal 6-Hydroxydopamine Parkinson’s disease rat modelPublication . Caridade-Silva, Rita; Araújo, Bruna; Martins-Macedo, Joana; Teixeira, Fábio G.Preventing degeneration and the loss of dopaminergic neurons (DAn) in the brain while mitigating motor symptoms remains a challenge in Parkinson’s Disease (PD) treatment development. In light of this, developing or repositioning potential disease-modifying approaches is imperative to achieve meaningful translational gains in PD research. Under this concept, N-acetylcysteine (NAC) has revealed promising perspectives in preserving the dopaminergic system capability and modulating PD mechanisms. Although NAC has been shown to act as an antioxidant and (neuro)protector of the brain, it has yet to be acknowledged how this repurposed drug can improve motor symptomatology and provide disease-modifying properties in PD. Therefore, in the present work, we assessed the impact of NAC on motor and histological deficits in a striatal 6-hydroxydopamine (6-OHDA) rat model of PD. The results revealed that NAC enhanced DAn viability, as we found that it could restore dopamine transporter (DAT) levels compared to the untreated 6-OHDA group. Such findings were positively correlated with a significant amelioration in the motor outcomes of the 6-OHDA-treated animals, demonstrating that NAC may, somehow, be a modulator of PD degenerative mechanisms. Overall, we postulated a proof-of-concept milestone concerning the therapeutic application of NAC. Nevertheless, it is extremely important to understand the complexity of this drug and how its therapeutical properties interact with the cellular and molecular PD mechanisms.
- 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.