Biology subjects

Farfara, D.

Publications and source records attributed to Farfara, D..

3 recordsLinked to original sources

bioRxiv2025

Circadian-Related Dynamics of the Endocannabinoid System in Male Mouse Brain

Endocannabinoids (eCBs) and related lipids play crucial roles in brain function, including the regulation of circadian rhythms and sleep. To comprehensively map these molecules, we employed liquid chromatography high-resolution tandem mass spectrometry (LC/HRMS/MS) to quantify 78 lipids across 14 families in seven brain areas of male mice at four time points throughout the day (every six hours), and during sleep initiation. We found that most eCBs from the fatty acids (FAs) family, particularly arachidonic acid (AA), were highly abundant in the mouse brain in all brain areas and during the circadian rhythm. High eCBs abundance was shown in deeper brain areas, while temporal differences using the Cosinor analysis revealed 26 eCBs behaving in a circadian rhythm response, with linolenic acid (LnA) being the only lipid to show rhythmicity across all brain areas. Sleep initiation (ZT1) was associated with increased N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) activity and N-acylethanolamide (NAE) levels in the cortex and hippocampus, while wake extension (WEx) altered 2-monoacylglycerol (2-MAG) metabolism and increased cannabinoid receptor 1 (CB1) expression. These findings provide a detailed lipidomic map of eCBs and related lipids in the male mouse brain, highlighting their area-specific distribution, circadian regulation, and involvement in sleep/wake transitions. Given the link between sleep disruption and neurodegeneration, future studies should investigate whether the observed eCB dysregulation contributes to sleep disturbances in these conditions, and if targeting these pathways offers novel therapeutic strategies. Significant StatementThis comprehensive study provides a high-dimensional map of eCBs and related lipids in the male mouse brain, revealing intricate spatial and temporal dynamics highlighting the role of these lipids in regulating fundamental physiological processes such as circadian rhythm and sleep.

neuroscience↗

bioRxiv2020

Remembering immunity: Neuronal ensembles in the insular cortex encode and retrieve specific immune responses

Increasing evidence indicates that the brain regulates peripheral immunity. Yet, it remains unclear whether and how the brain represents the state of the immune system. Here, we show that immune-related information is stored in the brains insular cortex (InsCtx). Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (DSS-induced colitis and Zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can encode and initiate specific immune responses, extending the classical concept of immunological memory to neuronal representations of immunity.

neuroscience↗

bioRxiv2017

Knockdown of Liver-Derived C1 Inhibitor Results in Brain Pathology in mice

Plasma proteins and activated immune cells are known contributors of vascular brain disorders. However, the mechanisms and routes involved are still unclear. In order to understand the cross-talk between plasma proteins and the brain, we knocked down circulating C1 inhibitor (C1INH) in wild-type (WT) mice using antisense-oligonucleotide (ASO) technique and examined the brain. C1INH is a plasma protein inhibitor of vascular inflammation induced by activation of the kallikrein-kinin system (KKS) and the complement system. This knockdown induced the activation of the KKS but spared the activation of the classical complement system. Activation of the KKS induced an upregulation of the bradykinin pathway in the periphery and the brain, resulting in hypotension. Blood-brain barrier (BBB) permeability, plasma protein extravasations, activated glial cells and elevated levels of IL-1beta, IL-6, TNF-alpha, and iNOS were detected in brains of C1INH ASO treated mice. Infiltrating innate immune cells were evident, entering the brain through the lateral ventricle walls and the neurovascular units. The mice showed normal motor functions, however, cognition was impaired. Altogether, our results highlight the important role of regulated plasma-C1INH as a gatekeeper of the neurovascular system. Thus, manipulation of C1INH in neurovascular disorders might be therapeutically beneficial.

neuroscience↗