Purpose: Vasoactive intestinal peptide (VIP) is an important regulator of lacrimal gland (LG) function although the effect of VIP on ductal fluid secretion is unknown. Therefore, the aim of the present study was to investigate the role of VIP in the regulation of fluid secretion of isolated LG ducts and to analyze the underlying intracellular mechanisms.
Methods: LGs from wild-type (WT) and cystic fibrosis transmembrane conductance regulator (CFTR) knockout (KO) mice were used. Immunofluorescence was applied to confirm the presence of VIP receptors termed VPAC1 and VPAC2 in LG duct cells. Ductal fluid secretion evoked by VIP (100 nM) was measured in isolated ducts using videomicroscopy. Intracellular Ca signaling underlying VIP stimulation was investigated with microfluorometry.
Results: VIP stimulation resulted in a robust and continuous fluid secretory response in isolated duct segments originated from WT mice. In contrast, CFTR KO ducts exhibited only a weak pulse-like secretion. A small but statistically significant increase was detected in the intracellular Ca level [Ca] during VIP stimulation in the WT and in CFTR KO ducts. VIP-evoked changes in [Ca] did not differ considerably between the WT and CFTR KO ducts.
Conclusions: These results suggest the importance of VIP in the regulation of ductal fluid secretion and the determining role of the adenylyl cyclase-cAMP-CFTR route in this process.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722779 | PMC |
Background: Progranulin (PGRN), a glycoprotein secreted by microglia and neurons, regulates lysosomal function, neuroinflammation, and has neurotrophic effects. Variants in the granulin gene (GRN) that cause a reduction of PGRN in plasma and cerebrospinal fluid (CSF) are associated with an increased risk of Alzheimer's disease (AD). The sortilin receptor (SORT1) on neurons and microglia regulates PGRN degradation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Introduction: Lecanemab (LEQEMBI®), a humanized monoclonal antibody targeting Amyloid-beta (Aβ) protofibrils, received full FDA approval in July 2023 for treating early-stage Alzheimer's disease (AD). This abstract highlights Tel Aviv Medical Center's (TLVMC) specialized infrastructure for early AD diagnosis and treatment and includes presenting baseline characteristics of initial patients opting for LEQEMBI®.
Methods: Outlining our clinics' operational experience in establishing the Center for advanced treatments for AD, treatment protocol, and a descriptive analysis of baseline assessment data including demographics, baseline Magnetic-Resonance-Imaging (MRI), Cerebrospinal-fluid (CSF)/PET biomarkers, pre-treatment cognitive evaluations (Mini-Mental-State-Examination (MMSE)/Montreal-Cognitive-Assessment (MoCA)), and Apolipoprotein-E (APOE) status.
Alzheimers Dement
December 2024
Laboratory of Neuro Imaging (LONI), University of Southern California, Los Angeles, CA, USA.
Background: Anti-amyloid therapy appears to have an increased effect on reducing cognitive decline in amyloid- and tau-positive individuals. However, clinical trials inclusion criteria require solely amyloid positivity. Herein, we developed a machine-learning prediction model to identify tau positivity in amyloid-positive individuals using clinical variables.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Laboratory of Neuro Imaging (LONI), University of Southern California, Los Angeles, CA, USA.
Background: Screen failure due to amyloid negativity is yet a problem in clinical trials for anti-amyloid drugs. In this context, clinical characteristics of patients presenting with cognitive decline may decrease the screen failure ratio by increasing the odds of selecting individuals with brain amyloid pathology. Herein, we aimed at estimating amyloid and tau positivity in individuals using clinical variables in a machine learning model of prediction.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
ki:elements GmbH, Saarbrücken, Germany.
Background: Changes in speech and language functions have shown to be early symptoms of AD pathology. Recent developments in automatic speech and language processing have opened avenues for objective assessments of these changes. The primary objective of this study is to explore whether speech and language markers extracted from cognitive testing conducted during an automated phone call differ according to underlying AD pathology as measured in cerebrospinal fluid (CSF) in preclinical or early stage individuals.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!