Percorrer por autor "Caridade-Silva, Rita"
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- Beyond the brain: The hidden role of cardiorenal dysfunction in Parkinson’s diseasePublication . Teixeira, C.; Araújo, B.; Caridade-Silva, Rita; Martins-Macedo, J.; Guedes,Carla; Gomes, Eduardo; Falcão-Pires, I.; Alencastre, I.; Teixeira, F.; Guedes, Carla; Gomes, EduardoParkinson’s disease (PD) is the second most common neurodegenerative disorder, marked by the progressive loss of dopaminergic neurons in critical areas of the brain, particularly the striatum and substantia nigra. PD's complex nature suggests its interactions with various systemic health issues, particularly those affecting organs outside the central nervous system (CNS), which may increase the risk of developing PD and affect treatment outcomes. Research indicates that individuals with cardiovascular disease (CVD) and chronic kidney disease (CKD) face significantly higher risks of PD, even when controlling for shared risk factors. Notably, alpha-synuclein aggregations, a hallmark of PD, have also been found in the renal and cardiac tissues of patients with PD, CKD, and CVD, highlighting the interconnectedness of these systems. The Zucker fatty and spontaneously hypertensive (ZSF1) rats model metabolic syndrome, which includes kidney issues and heart failure. This study aimed to explore how the ZSF1 phenotype impacts the integrity of dopaminergic neurons and neuroinflammatory processes. Brain tissues from ZSF1 rats were analyzed through immunostaining with markers specific to dopaminergic and glial cells. The results showed a significant decrease in dopaminergic markers in the striatum and substantia nigra, indicating a potential link between cardiorenal dysfunction and neurodegenerative pathways. These findings suggest that systemic health conditions can directly influence PD pathology, emphasizing the complex interactions between the brain, heart, and kidneys, and presenting new opportunities for targeted PD therapies.
- 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.
- 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.
- The synergy of dopaminergic system and adult hippocampal neurogenesis in a pre-clinical model of Parkinson’s disease pp85Publication . Araújo, B.; Caridade-Silva, Rita; Vilaça-Ferreira, A.; Martins-Macedo, J.; Teixeira, C.; Soares-Guedes, C.; Svenningsson, P.; Pinto, L.; Teixeira, F.; Guedes, CarlaDepressive disturbances are prevalent in 40% to 50% of clinical cases of Parkinson’s Disease (PD), alongside a common reduction in adult hippocampal neurogenesis observed in both PD and its related conditions. This neurogenesis deficit may affect the clinical course of the disease. With this in mind, we set an experiment using the glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rat model to assess the impact of impaired adult cytogenesis induced by the antiviral Ganciclovir on PD. The experiment involved a combination of the GFAP-TK model and a 6-hydroxydopamine (6-OHDA) model of PD, while behavioral analyses focused on anxiety, depression, and motor skills. From the results, histological examinations revealed decreased proliferative cells and reduced dopaminergic innervation. Additionally, analysis of newborn and immature neurons occurred in the hippocampus, subventricular zone, and olfactory bulbs, while dopaminergic loss was assessed in regions like the substantia nigra and striatum. Findings indicated that the model exhibited anxiety/depressive-like behaviors and motor impairments, linked to the notable loss of dopaminergic neurons, which appeared to correlate with reduced doublecortin-positive cells in the hippocampus. Moreover, results suggested subtle differences between ipsilateral and contralateral sides, highlighting the dopaminergic system's role in hippocampal adaptation. Therefore, these findings suggest a connection between reduced neurogenesis and dopaminergic neuron loss, hinting that these phenomena might be interrelated. Therefore, investigating this potential regional interconnection may augment our understanding of non-motor dimensions in PD pathophysiology related to motor functions, thereby facilitating the development of enhanced therapeutic strategies for individuals in the early stages of PD.