Biology subjects

Crespi, C.

Publications and source records attributed to Crespi, C..

3 recordsLinked to original sources

bioRxiv2024

Oral cannabidiol administration in mice during pregnancy and lactation affects early postnatal body weight, fasting glucose, ingestive behavior, anxiety- and obsessive compulsive-like behaviors, and long-term object-memory in adult offspring in a sex-dependent manner

RationaleThe consequences of perinatal cannabidiol (CBD) exposure are severely understudied, but are important, given its widespread use and believed safety as a natural supplement. ObjectiveThe objective of this study was to test the health, metabolic, and behavioral consequences of perinatal CBD exposure on dams and their offspring raised to adult. MethodsPrimiparous female C57BL/6J mice were orally administered 100 mg/kg CBD in strawberry jam to expose offspring during gestation, lactation, or both using a cross-fostering design. Adult offspring were metabolically profiled using indirect calorimetry and intraperitoneal glucose tolerance testing. Adults were behaviorally phenotyped, video recorded, and mouse position tracked using DeepLabCut. ResultsCBD was detected in maternal plasma using LC-MS 10-min post consumption (34.2 {+/-} 1.7 ng/ul) and peaked within 30 min (371.0 {+/-} 34.0 ng/ul). Fetal exposure to CBD significantly decreased survival of the pups, and decreased male postnatal development, but did not alter litter size, maternal body weight or pup birth weight. We observed many sex-dependent effects of perinatal CBD exposure. Exposure to CBD during gestation and lactation increased meal size, caloric intake, and respiratory exchange ratio for adult male offspring, while exposure during lactation decreased fasting glucose, but had no effect on clearance. Adult female offspring exposed to CBD during lactation showed increased drink size. Perinatal CBD exposure increased obsessive compulsive- and decreased anxiety-like behaviors (marble burying, light-dark box, elevated-plus maze) in female mice, decreased long-term object memory in male mice, and had no effect on attention tasks for either sex. ConclusionsWe conclude that orally-administered CBD during pregnancy affects behavior and metabolism in a sex-dependent manner, and mice are differentially sensitive to exposure during gestation vs. lactation, or both. Because long-term changes are observed following perinatal exposure to the drug, and exposure significantly decreases survival to weaning, more research during development is warranted. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/602955v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1a9341dorg.highwire.dtl.DTLVardef@19c7356org.highwire.dtl.DTLVardef@5833baorg.highwire.dtl.DTLVardef@ac153c_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LIMice can be trained to orally consume CBD using strawberry jam as the vehicle. C_LIO_LICBD administration to pregnant dams decreases pup survival to weaning age without significantly affecting maternal behavior. C_LIO_LIPerinatal CBD exposure decreases developmental body weight in males. C_LIO_LIGestational or lactational CBD increases the respiratory exchange ratio (RER), increases mean meal and drink size, and reduces fasting glucose in a sex-dependent manner. C_LIO_LICBD increases obsessive-compulsive like behavior in adult offspring, which could be eliminated in females by cross-fostering to a drug-free dam. C_LIO_LIPerinatal CBD selectively decreases anxiety-like behavior in females and decreases long-term object memory in males. C_LI

neuroscience↗

bioRxiv2023

Host factor PLAC8 is required for pancreas infection by SARS-CoV-2

BackgroundAlthough COVID-19 initially caused great concern about respiratory symptoms, mounting evidence shows that also the pancreas is productively infected by SARS-CoV-2. However, the severity of pancreatic SARS-CoV-2 infection and its pathophysiology are still under debate. Here we investigated the consequences of SARS-CoV-2 pancreatic infection and the role of the host factor Placenta-associated protein (PLAC8) MethodsWe analyzed plasma levels of pancreatic enzymes and inflammatory markers in a retrospective cohort study of 120 COVID-19 patients distributed in 3 severity-stratified groups. We studied the expression of SARS-CoV-2 and PLAC8 in the pancreas of deceased COVID-19 patients as well as in non-infected donors. We performed infection experiments in PLAC8 knock-out PDAC cell lines with full SARS-CoV-2 virus. ResultsWe found that analysis of circulating pancreatic enzymes aided the stratification of patients according to COVID-19 severity and predict outcomes. Interestingly, we found an association between PLAC8 expression and SARS-CoV-2 infection in postmortem analysis of COVID-19 patients. Using full SARS-CoV-2 infectious virus inoculum from Wuhan-1 and BA.1 strains, we demonstrated that PLAC8 is necessary for productive infection of PDAC cell lines. Finally, we observed an overlap between PLAC8 and SARS-CoV-2 immunoreactivities of the pancreas of deceased patients. ConclusionOur data indicate the human pancreas as a SARS-CoV-2 target with plausible signs of injury and demonstrate that the host factor PLAC8 is required for SARS-CoV-2 pancreatic infection, thus defining new target opportunities for COVID-19-associated pancreatic pathogenesis. Plain language summaryPrevious studies have shown that the pancreas is infected by SARS-CoV-2. However, none of these studies have described measurable pancreatic damage associated to COVID-19 severity and the pathogenesis of pancreatic SARS-CoV-2 infection remains largely unknown. Novel host factors have been proposed for SARS-CoV-2 infection of mainly the airway epithelium, none of them studied in the pancreas. Our study shows clinically relevant pancreatic damage associated with SARS-CoV-2 infiltration and assesses the predictive potential of circulating pancreatic enzymes to stratify patients according to COVID-19 severity and predict clinical outcomes in a cohort of 120 patients. Our data show that host factor Placenta-associated protein 8 (PLAC8) expression is linked to SARS-CoV-2 infection in postmortem analysis of COVID-19 patients and functionally demonstrated the full requirement of PLAC8 for SARS-CoV-2 pancreatic infection and viral replication. Our data confirm the human pancreas as a SARS-CoV-2 target with signs of injury unveiling the measurement of pancreatic enzymes for prognosis value and demonstrating that host factor PLAC8 is required for SARS-CoV-2 pancreatic infection defining new stratification and target opportunities for COVID-19-associated pancreatic pathogenesis.

cell biology↗

bioRxiv2022

GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility.

Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and healthy control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility.

molecular biology↗