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O receptor P2X7 microglial orquestra neuroinflamação, disfunção autofágica e sinucleinopatia em ratos parkinsonianos

Wed, 01 Jan 2025 00:00:00 GMT

Título: O receptor P2X7 microglial orquestra neuroinflamação, disfunção autofágica e sinucleinopatia em ratos parkinsonianos Autor(es): Nascimento, Tyciane de Souza Abstract: Parkinson’s disease (PD) is a multisystem neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the presence of protein inclusions known as Lewy bodies, which are primarily composed of aggregated α-synuclein. Under physiological conditions, these proteins are targeted for autophagic degradation. Hyperactivity of purinergic P2X7 receptors has been extensively implicated in the pathophysiology of PD, with growing evidence supporting their role in autophagic dysfunction and protein aggregation. Thus, the present study aimed to investigate the neuroprotective effect of the P2X7 receptor antagonist Brilliant Blue G (BBG), administered during a prodromal phase of PD, focusing on its impact on α-synuclein accumulation and dysfunction of autophagic pathways in an experimental model of rotenone-induced parkinsonism. For this purpose, male Wistar rats were divided into four groups: control, control treated, parkinsonian (rotenone 2.75 mg/kg for 21 days, intraperitoneally), and parkinsonian treated with BBG (50 mg/kg for 15 days, intraperitoneally). Animals were subjected to behavioral tests and, at the end of the protocol, euthanized for brain collection for immunohistochemical and molecular analyses. P2X7 receptor blockade significantly protected the animals against deficits in volatile odor detection, locomotor activity (open field test), motor coordination (rotarod test), depressive-like behavior (sucrose preference test), and working memory (Y-maze test) induced by rotenone exposure. BBG prevented the loss of dopaminergic neurons in the substantia nigra and striatum, reduced neuroinflammation, and decreased the accumulation of total and phosphorylated α- synuclein. Additionally, BBG modulated autophagic and mitophagic pathways, as evidenced by reduced expression of proteins such as LC3 and PINK1. The effect of BBG occurred by decreasing the number of microglial P2X7 receptors. The results indicate that rotenone-induced microglial purinergic hyperactivity acts as a multifaceted pathogenic integration center, amplifying neuroinflammation, disrupting autophagic processes, and promoting the accumulation of pathogenic α-synuclein, thereby creating a vicious cycle that culminates in dopaminergic neuronal death. Thus, P2X7 receptor blockade emerges as a promising therapeutic approach for targeting multiple pathological pathways in PD. Tipo: Tese

Investigação de testes de sarcopenia como preditores de quedas na doença de Parkinson leve a moderada: estudo de coorte prospectivo

Sun, 01 Jan 2023 00:00:00 GMT

Título: Investigação de testes de sarcopenia como preditores de quedas na doença de Parkinson leve a moderada: estudo de coorte prospectivo Autor(es): Gomes, Vlademir Carneiro Abstract: Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease in Brazil, affecting 1% of the elderly population aged over 65 years and 4 to 5% of those aged over 85 years. It is a chronic and progressive central nervous system disorder associated with a decreased quality of life and functional impairment. The prevalence of falls in elderly individuals with PD is higher than in the general population, with an annual risk of falls ranging from 45% to 68%. It is known that there are differences between single fallers and recurrent fallers, but there are limited studies addressing this context. Sarcopenia is a complex and multifactorial condition characterized by a progressive and generalized reduction in the quantity and quality of skeletal muscle tissue. Currently considered a global public health issue, sarcopenia is associated with an increased risk of falls, fractures, functional impairment, and mortality in the elderly. The objective of this study was to investigate predictive factors for recurrent and non-recurrent falls based on the diagnostic criteria of sarcopenia in patients with mild to moderate Parkinson's Disease. This was a cohort study conducted at the Hospital Universitário Walter Cantidio in Fortaleza, Ceará, with patients from the Movement Disorders outpatient clinic of the Neurology department from March 2021 to March 2023. To be eligible, patients needed to have a confirmed diagnosis of PD, a Hoehn and Yahr severity stage between 1 and 3, and the ability to stand and walk independently. Individuals with severe medical problems or uncontrolled chronic diseases were excluded. Demographic and clinical data, anthropometric measurements, cognitive assessment using the Mini-Mental State Examination, evaluation of depressive symptoms using the Geriatric Depression Scale, assessment of parkinsonian symptoms using the Unified Parkinson's Disease Rating Scale, fall history, and sarcopenia assessment based on the Revised European Consensus on Sarcopenia recommendations were collected during the patients' regular appointments. Each patient received a questionnaire to fill out in case of falls during the 12-month period. Monthly phone calls were made to check for fall occurrences. The study sample consisted of 103 patients, of whom 38 (37%) were women and 65 (63%) were men, with an average age of 66 ± 10.5 years. Higher SARC-F scores and a longer disease duration were independent predictors of recurrent and non-recurrent falls over a 12-month period. Tipo: Dissertação

Efeitos da liraglutida, um agonista do receptor do peptídeo-1 semelhante ao glucagon (GLP-1), sobre parâmetros metabólicos e saciedade de pacientes com lipodistrofia generalizada congênita

Thu, 01 Jan 2026 00:00:00 GMT

Título: Efeitos da liraglutida, um agonista do receptor do peptídeo-1 semelhante ao glucagon (GLP-1), sobre parâmetros metabólicos e saciedade de pacientes com lipodistrofia generalizada congênita Autor(es): Araújo, Jéssica Silveira Abstract: Lipodystrophies comprise rare, often underdiagnosed conditions characterized by partial or complete loss of subcutaneous adipose tissue, resulting in ectopic fat deposition in organs such as the pancreas, skeletal muscle, and liver, which may lead to severe metabolic complications. The spectrum of these complications is directly related to the extent of body fat loss, with generalized forms exhibiting more pronounced metabolic impairment and hyperphagia driven by markedly low leptin levels. The literature on the effects of glucagon-like peptide-1 receptor agonists in patients with lipodystrophies remains limited. Therefore, this study represents the first to evaluate the effects of liraglutide on metabolic parameters and satiety in patients with congenital generalized lipodystrophy (CGL). This open-label interventional study included patients with CGL followed by the Brazilian Group for the Study of Hereditary and Acquired Lipodystrophies (BRAZLIPO), who received liraglutide for 12 weeks. Metabolic outcomes were assessed at baseline, after treatment (week 12), and following an additional 12-week off- treatment period (week 24), with complementary evaluation of body composition, satiety, and hepatic imaging. Changes over time were analyzed using the Friedman test, with a significance level set at 5%. Eight patients were included (aged 24–45 years, six females); gastrointestinal adverse events led to treatment discontinuation in three patients. After 12 weeks of liraglutide therapy, a median reduction in HbA1c (−2.5%; range 1.1 to 3.1%; p=0.012) and in total daily insulin dose (−20%; range 0 to 100%; p=0.042) was observed, along with a non-significant reduction in triglycerides (−127 mg/dL; range 64 to 1171 mg/dL; p=0.350). Following treatment discontinuation, all patients exhibited increases in HbA1c and body weight of 2.2% (range 0.8 to 3.5%; p=0.026) and 3.6% (range 3.5 to 4.7%; p=0.001), respectively. Triglyceride levels increased in 80% of patients (median 421.5 mg/dL; range 76 to 1649; p=0.334). Insulin requirements also increased overall, with one patient resuming insulin at 0.4 U/kg/day and the others showing a median dose increase of 22% (range 12 to 50%; p=0.024). This study provides the first evidence that liraglutide may confer metabolic benefits in patients with CGL. Larger and longer-term studies are warranted to better characterize its effects on satiety, body composition, and liver disease in this population. Tipo: Dissertação

Envolvimento de biomarcadores endoteliais na chikungunya crônica

Thu, 01 Jan 2026 00:00:00 GMT

Título: Envolvimento de biomarcadores endoteliais na chikungunya crônica Autor(es): Furtado, Frederico Luis Braz Abstract: Introduction: Chikungunya is an arboviral disease responsible for triggering an intense inflammatory response, associated with long-lasting clinical manifestations in chronic cases. In the last decade, it has affected millions of people in the Americas, Africa, Asia, and Europe, becoming a major public health problem due to its significant impact on quality of life. In this context, the study of endothelial biomarkers can contribute to clarifying the prognosis of the disease and its clinical repercussions. Objective: To investigate biomarkers of endothelial injury in chronic chikungunya. Materials and methods: Cross-sectional study with 34 chronic cases, selected from the cohort of the Oliveira Pombo Basic Health Unit, linked to the “Study of the natural history and therapeutic response of Chikungunya focusing on acute and chronic musculoskeletal manifestations in Fortaleza-CE”. Venous blood samples were collected for the measurement of endothelial biomarkers (ANG-2, VCAM-1, and SYN- 1), in addition to clinical data, such as comorbidities and symptoms, extracted from the cohort questionnaires. Results: The mean age of chronic cases was 45.11 ± 15.86 years, with 28 (76.47%) being female. Twenty (58.82%) participants belonged to the group with 360 days of disease duration. The most prevalent symptoms were morning stiffness (28; 82.35%), arthralgia (22; 64.71%), and edema (16; 47.06%). In the comparison between the three groups of chronic patients with different disease durations (180, 360, and 720 days) and the control group, the biomarkers ANG-2, VCAM-1, and SYN-1 showed statistically significant differences (p = 0.007; p = 0.004; p < 0.001, respectively). Increased levels of ANG-2 (p = 0.037) were observed in patients with and without depression, as well as reductions in VCAM-1 (p = 0.047) and SYN-1 (p = 0.036) in cases with and without memory impairment. SYN-1 levels were increased in patients with fever (p = 0.041) and reduced in those with blurred vision (p = 0.019) and alopecia (p = 0.009), compared to those without these symptoms. Only the biomarkers ANG-2 and VCAM-1 showed a correlation with disease duration, with a moderate and positive correlation for ANG-2 (Rho = 0.456; p = 0.006) and a weak and negative correlation for VCAM-1 (Rho = -0.369; p = 0.034). ANG-2 was the only biomarker with good predictive performance in the AUC-ROC curve = 0.864 and 95% CI (0.725 - 1000), while VCAM-1 and SYN-1 presented, respectively, AUC-ROC = 0.605 and 95% CI (0.338 – 0.872); AUC-ROC = 0.519 and 95% CI (0.148 – 0.890). Conclusion: Increased levels of ANG-2 and reduced levels of VCAM-1 were associated with disease duration in the evaluated cases. SYN-1 may be related to the presence of symptoms such as fever, memory impairment, blurred vision, and alopecia in patients with chronic chikungunya. Tipo: Tese