Biology subjects

Lopes Salles, E.

Publications and source records attributed to Lopes Salles, E..

3 recordsLinked to original sources

bioRxiv2025

Rethinking Alzheimer's: Harnessing Cannabidiol to Modulate IDO and cGAS Pathways for Neuroinflammation Control

Alzheimers disease has traditionally been associated with amyloid-{beta} plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoimmune hypothesis of Alzheimers disease suggests chronic inflammation and immune dysfunction contribute to neuronal damage, making modulation of immune responses a promising therapeutic strategy for the disease. Cannabidiol, a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential. This study explores how cannabidiol influences the Indoleamine 2,3-dioxygenase (IDO) and cyclic GMP-AMP synthase (cGAS) pathway, a key regulator of neuroinflammation in Alzheimers disease. Using the 5XFAD transgenic mouse model of Alzheimers disease, we administered cannabidiol via inhalation. We assessed immune markers, including Indoleamine 2,3-dioxygenase and cyclic GMP-AMP synthase, through flow cytometry, immunofluorescence staining, and gene expression analysis. Cytokine levels and neuroinflammatory responses were evaluated, and protein-protein interactions within the Indoleamine 2,3-dioxygenase/cyclic GMP-AMP synthase pathway were analyzed using the STRING database. Cannabidiol treatment significantly reduced Indoleamine 2,3-dioxygenase and cyclic GMP-AMP synthase expression, correlating with lower levels of pro-inflammatory cytokines, including Tumor Necrosis Factor-alpha, Interleukin-1 beta, and Interferon-gamma. Bioinformatics analysis identified potential interactions between cannabidiol and immune targets such as Protein Kinase B (AKT1), Transient Receptor Potential Vanilloid 1, and G-protein coupled receptor 55, suggesting a multi-targeted therapeutic effect. These findings support cannabidiol as a potential monotherapy or adjunctive treatment for Alzheimers disease, targeting neuroinflammatory pathways, particularly the Indoleamine 2,3-dioxygenase/cyclic GMP-AMP synthase axis. Further studies are needed to explore its full therapeutic potential.

immunology↗

bioRxiv2024

Optimization of Seizure Prevention by Cannabidiol (CBD)

ObjectiveCannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived, pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study. MethodsWe evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral and injection routes. We used CBD broad spectrum (inhaled and injection) versus CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring Immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups. ResultsOur findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested. CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p<0.05) compared to other forms of CBD treatments. ConclusionOur data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, warrants further research.

neuroscience↗

bioRxiv2024

The role of dietary patterns in the polarization of angiogenic uterine Natural Killer cells during murine pregnancy

Uterine Natural Killer (uNK) cells, predominant leukocytes in mouse and human pregnant uteruses, play crucial roles in angiogenesis and pregnancy protection. In mice, DBA lectin-reactive uNK cells expressing Gal-N-Ac sugar exhibit angiogenic functions essential for pregnancy maintenance. This study compares the impact of different nutritional imbalances on mouse pregnancy and the activation of angiogenic DBA+ uNK cells to safeguard against pregnancy complications. High Fat (HF), High Carbohydrate (HC), High Protein (HP), and Food Restriction (FR) diets were administered from gestation day (GD) 1 to GD10 or until parturition. HF and HC diets led to reduced expression of DBA-identified N-acetyl-D-galactosamine, akin to LPS-induced inflammation, and decreased uNK perforin levels. Additionally, HF and HC diets resulted in elevated endometrial cleaved caspase-3 and decreased smooth muscle alpha-actin, causing blood vessel wall thinning without jeopardizing pregnancy term. FR impaired uNK differentiation, manifesting as an "all-or-none" phenomenon with 50% pregnancy failure. Our findings highlight the intricate relationship between nutritional imbalances and mouse pregnancy outcomes. Notably, high-fat diets elicited pronounced responses from DBA+ uNK cells, while high-protein diets had relatively weaker effects. This study underscores the importance of comprehending uNK cell dynamics in maintaining pregnancy homeostasis under diverse dietary conditions, paving the way for elucidating molecular mechanisms governing these interactions. By shedding light on these complex relationships, this research offers valuable insights for improving maternal and fetal health in the context of nutritional interventions during pregnancy.

immunology↗