Biology subjects

Siopi, E.

Publications and source records attributed to Siopi, E..

4 recordsLinked to original sources

bioRxiv2026

Parathyroid Hormone Receptor 1 Signaling Encodes Multifaceted Metabolic Programs in AgRP Neurons

Organisms continuously adapt food intake and nutrient utilization to fluctuating energy demands, requiring the brain to accurately integrate signals coming from diverse metabolic organs and local signals into distinct physiological responses. How hypothalamic neurons discriminate these signals to independently regulate feeding behavior and peripheral metabolism remains poorly understood. In recent years, a coordinated regulation between bone physiology and the central control of energy metabolism has emerged, opening questions about potential common hormonal networks and signaling pathways between the bone and the brain. Here, we identify parathyroid hormone receptor 1 (PTH1R) signaling, a master regulator of calcium ion biochemistry and bone formation, in Agouti-related peptide (AgRP) neurons as an unexpected neuroendocrine mechanism for the control of feeding behaviourand nutrient partitioning. the two cognate endocrine and paracrine ligands, PTH and PTH-related peptide (PTHrP), selectively activat segregated intracellular kinases activation and lipophagic processes in AgRP neuron, ultimately producing convergent physiological outputs. Together, our findings identify the parathyroid hormonal system acts as a fine-tuning mechanism in specialized neuronal circuits allowing for hypothalamic adaptive responses to energy demands and systemic metabolic signals. Keywords: Parathyroid hormone-related peptide (PTHrP), hypothalamus, arcuate nucleus, agouti-related peptide neurons, energy metabolism, fasting, autophagy, free fatty acids

neuroscience↗

bioRxiv2025

Progressive muscle metabolic reprogramming in asymptomatic ALS gene mutation carriers

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disorder characterized by motor neuron loss leading to extensive paralysis. There is emerging evidence that the disease involves a prolonged presymptomatic period during which motor function is preserved. Understanding the molecular mechanisms involved is key as the presymptomatic phase represents a critical window of opportunity for early intervention. Using RNA sequencing, we investigated changes in gene expression patterns in the skeletal muscle of ten asymptomatic carriers of ALS mutations (8 C9ORF72 expansion carriers and 2 SOD1 mutation carriers). We found that specific modifications of gene expression profiles are present in skeletal muscle before asymptomatic ALS gene carriers exhibit biomarker changes predictive of phenoconversion. We identified insulin signaling, AMPK signaling, and thermogenesis pathways, together with the TCA cycle as the main contributors to the dysregulated muscle transcriptome. Our data suggest that this metabolic reprogramming of skeletal muscle develops progressively during the transition to phenoconversion, characterized by a gradual increase in the expression of SREBF1 which encodes SREPB1, the key transcriptional regulator of lipid synthesis, in parallel with the progressive activation of AMPK and insulin signaling pathways. Our findings are consistent with a progressive enhancement in fatty acid metabolism and oxidative capacity in skeletal muscle, followed by a decline in oxidative phosphorylation efficiency as phenoconversion approaches. Evidence of muscle metabolic reprogramming in ALS long before motor onset identifies the dysregulation of muscle energy homeostasis as a critical early event in ALS pathogenesis. One sentence summarySkeletal muscle from individuals at elevated genetic risk for ALS/FTD undergoes progressive metabolic reprogramming far before disease onset.

neuroscience↗

bioRxiv2019

The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system

Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota, but causality remains yet to be established. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that the UCMS mice display phenotypic alterations -- characterized by an altered gut microbiota composition, a reduced adult hippocampal neurogenesis and a depressive-like behaviors -- which could be transferred from UCMS donors to naive recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota on adult neurogenesis and behavior in naive recipient mice were alleviated by selectively enhancing the central eCB tone or by adding arachidonic acid, a fatty acid precursor of eCB ligands, to the diet. In the gut of both UCMS donors and recipients, the microbiota composition was characterized by a relative decrease in Lactobacilli abundance, and complementation of the UCMS recipient microbiota with a strain of the Lactobacilli genus was sufficient to restore normal eCB brain levels, hippocampal neurogenesis and to alleviate depressive-like behaviors. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota dysbiosis generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.

neuroscience↗

bioRxiv2019

Gut microbiota requires vagus nerve integrity to promote depression

Chronic stress constitutes one of the strongest risk factors for depression and can disrupt various aspects of homeostasis, including gut microbiota composition. We found that stress-induced changes in gut microbiota promote depression and decrease adult hippocampal neurogenesis upon transfer to antibiotic-treated recipient mice. Subdiaphragmatic vagotomy abrogated the microbiota-induced effects on behavior and neurogenesis, suggesting that gut microbiota can influence brain plasticity and behavior through vagal afferents.

neuroscience↗