Biology subjects

Nasri, A.

Publications and source records attributed to Nasri, A..

3 recordsLinked to original sources

bioRxiv2024

Cerebral Venous Blood Flow Regulates Brain Fluid Clearance via Dural Lymphatics

The vascular system regulates brain clearance through arterial blood flow and lymphatic drainage of cerebrospinal fluid (CSF). Idiopathic intracranial hypertension (IIH), characterized by elevated intracranial pressure and dural venous sinus stenoses, can be treated by restoring venous blood flow via venous stenting, suggesting a role for venous blood flow in brain fluid clearance. Using magnetic resonance imaging (MRI) in IIH patients and healthy controls, we identified that dural venous stenoses in IIH were associated with impaired lymphatic drainage, perivenous fluid retention, and brain fluid accumulation. To investigate this further, we developed a mouse model with bilateral jugular vein ligation (JVL), which recapitulated key human findings, including intracranial hypertension, calvarial lymphatic regression, and brain swelling due to impaired clearance. To further dissect the respective roles of dural lymphatics and venous blood flow in brain clearance, we performed JVL in mice with dural lymphatic depletion. These mice exhibited spontaneous elevated intracranial pressure, but JVL did not further exacerbate this effect. Moreover, the synchronous restoration of brain clearance and dural lymphatics observed in mice after JVL was absent in lymphatic-deficient mice.Transcriptomic analyses revealed that lymphatic remodeling induced by JVL was driven by VEGF-C signaling between dural mesenchymal and lymphatic endothelial cells. These findings establish the dural venous sinuses as a critical platform where venous blood flow interacts with mesenchymal cells to preserve dural lymphatic integrity and function, essential for brain fluid clearance.

neuroscience↗

bioRxiv2024

Nucleobindin-1 (Nucb1) disruption affects feeding, metabolism, and glucose homeostasis in mice in an age-, sex-, diet- and light cycle-dependent manner

BackgroundNesfatin-1 (NESF-1), encoded in the calcium and DNA binding protein (Nucleobindin 2, NUCB2) is an orphan ligand with metabolic effects. Recently, our lab provided evidence for a NESF-1-like peptide (NLP) in a NUCB2-related precursor, NUCB1, in zebrafish and rodents. This research aims to determine whether endogenous NUCB1 is critical for energy homeostasis. Methods and Main FindingsGlobal genetic disruption of Nucb1 (Nucb1 knockout/KO mice) led to increased food intake in chow-fed male and female mice across different points of light and dark phases. A similar increase in water intake was seen in female Nucb1 KO mice but not in males. White adipose tissue weight was significantly increased in male and female Nucb1 KO mice. Dark phase total activity was increased in male Nucb1 KO mice, while it was decreased in female Nucb1 KO mice compared to wildtype littermates. Energy derived from carbohydrates was raised during the dark phase; while energy derived from fat was significantly decreased in both male and female Nucb1 KO mice. Male Nucb1 KO mice were lighter in the early stages, but these differences disappeared as they aged. Meanwhile, no differences in bodyweight were observed in female Nucb1 KO mice. Male Nucb1 KO mice handled glucose better during an oral glucose tolerance test, while the opposite effect was found in an intraperitoneal (IP) glucose tolerance test. The above results from chow-fed mice were largely true in 10% and 60% fat diet-fed mice. A significant two-way interaction between mice group and time was observed on weekly food intake of male and female Nucb1 KO mice fed control fat diet, but not in 60% fat-fed group. Handling of blood glucose during IPGTT was better in male Nucb1 KO mice fed both diets, while such an effect was not observed in female KO mice. A significant two-way interaction of mice group and time on food and water intake value in 24 h was observed for male Nucb1 KO mice fed 10% fat diet. The total physical activity during the dark phase and energy expenditure during the light phase showed a sex-specific pattern in male and female Nucb1 KO mice fed 10% fat diet. Energy expenditure showed a sex-specific pattern in Nucb1 KO mice during the dark phase. Moreover, adiposity increased in male Nucb1 KO mice fed a high fat diet. ConclusionsOur results indicate that the disruption of Nucb1 leads to metabolic changes in vivo. The phenotype appears to depend on sex, age, diet, and the light-dark cycle. In conclusion, these outcomes furnish important evidence supporting critical roles for endogenous NUCB1 in energy homeostasis.

physiology↗

bioRxiv2023

Human airway ex vivo models: new tools to study the airway epithelial cell response to SARS-CoV-2 infection

Airway-liquid interface cultures of primary epithelial cells and of induced pluripotent stem cell-derived airway epithelial cells (ALI and iALI, respectively) are physiologically relevant models for respiratory virus infection studies because they can mimic the in vivo human bronchial epithelium. Here, we investigated gene expression profiles in human airway cultures (ALI and iALI models) infected or not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using publicly available and our own bulk and single-cell transcriptome datasets. SARS-CoV-2 infection significantly increased the expression of interferon-stimulated genes (IFI44, IFIT1, IFIT3, IFI35, IRF9, MX1, OAS1, OAS3 and ISG15) and inflammatory genes (NFKBIA, CSF1, FOSL1, IL32 and CXCL10) at day 4 post-infection, indicating activation of the interferon and immune responses to the virus. Extracellular matrix genes (ITGB6, ITGB1 and GJA1) also were altered in infected cells. Single-cell RNA sequencing data revealed that SARS-CoV-2 infection damaged the respiratory epithelium, particularly mature ciliated cells. The expression of genes encoding intercellular communication and adhesion proteins also was deregulated, suggesting a mechanism to promote shedding of infected epithelial cells. These data demonstrate that ALI/iALI models help to understand the airway epithelium response to SARS-CoV-2 infection and are a key tool for developing COVID-19 treatments.

cell biology↗