A putative lysophosphatidylinositol receptor GPR55 modulates hippocampal synaptic plasticity.

GPR55, an orphan G-protein coupled receptor, is activated by lysophosphatidylinositol (LPI) and the endocannabinoid anandamide, as well as by other compounds including THC. LPI is a potent endogenous ligand of GPR55 and neither GPR55 nor LPIs' functions in the brain are well understood. While endocannabinoids are well known to modulate brain synaptic plasticity, the potential role LPI could have on brain plasticity has never been demonstrated. Therefore, we examined not only GPR55 expression, but also the role its endogenous ligand could play in long-term potentiation, a common form of synaptic plasticity. Using quantitative RT-PCR, electrophysiology, and behavioral assays, we examined hippocampal GPR55 expression and function. qRT-PCR results indicate that GPR55 is expressed in hippocampi of both rats and mice. Immunohistochemistry and single cell PCR demonstrates GPR55 protein in pyramidal cells of CA1 and CA3 layers in the hippocampus. Application of the GPR55 endogenous agonist LPI to hippocampal slices of GPR55+/+ mice significantly enhanced CA1 LTP. This effect was absent in GPR55-/- mice, and blocked by the GPR55 antagonist CID 16020046. We also examined paired-pulse ratios of GPR55-/- and GPR55+/+ mice with or without LPI and noted significant enhancement in paired-pulse ratios by LPI in GPR55+/+ mice. Behaviorally, GPR55-/- and GPR55+/+ mice did not differ in memory tasks including novel object recognition, radial arm maze, or Morris water maze. However, performance on radial arm maze and elevated plus maze task suggests GPR55-/- mice have a higher frequency of immobile behavior. This is the first demonstration of LPI involvement in hippocampal synaptic plasticity.

The seroprevalence of SARS-CoV-2 in a rural southwest community.

Context: The true prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has been difficult to determine due to limited testing, inconsistent symptom severity, and asymptomatic infections. Systematic investigation of the prevalence of SARS-CoV-2 has been limited to urban environments and large academic centers. Limited data on the seroprevalence of SARS-CoV-2 is available for those who live in a rural community setting, leaving rural practitioners to extrapolate the epidemiology of COVID-19 to a nonhomogeneous population. Objective: To determine the seroprevalence of SARS-CoV-2 in a community setting. The secondary objective of this study was to describe the difference in infection rate and reverse transcription polymerase chain reaction (RT-PCR) testing in the same rural community. Methods: A prospective convenience sample of community members and healthcare workers from the Kingman, Arizona area were tested for SARS-CoV-2-specific antibodies using a lateral flow immunoassay with the VITROS Anti-SARS-CoV-2 IgG test (Ortho-Clinical Diagnostics, Inc.) from September 28, 2020 to October 09, 2020. Upon recruitment, participants were asked to complete a demographic survey assessing socioeconomic status, comorbidities, and COVID-19 symptoms in the preceding two months. Following enrollment, a retrospective chart review was completed to determine the percentage of patients who had undergone previous SARS-CoV-RT-PCR testing. Results: A total of 566 participants were included in the final analysis: 380 (67.1%) were women, 186 (32.9%) were men, a majority (458; 80.9%) self-identified as White, and 303 (53.5%) were employed as healthcare professionals. Seroprevalence of SARS-CoV-2 was found to be 8.0% (45 of 566) across the sample and 9.9% (30 of 303) in healthcare workers. No statistical difference in seroprevalence was found between men and women, healthcare workers and other participants, amongst racial groups, by socioeconomic status, by comorbid conditions, or by education level. Among the participants, 108 (19.1%) underwent previous RT-PCR testing. Of the 45 patients who were antibody positive, 27 (60%) had received a previous RT-PCR test, with 20 (44.4%) testing positive for SARS-CoV-2. Participants with symptoms of anosmia/ageusia (p<0.001), chest congestion (p=0.047), fever (p=0.007), and shortness of breath (p=0.002) within the past two months were more likely to have antibodies to SARS-CoV-2. Conclusion: Only 8% of 566 participants in this rural community setting were found to have antibodies for SARS-CoV-2. A large minority (18; 40%) of patients testing seropositive for SARs-CoV-2 had never received a prior test, suggesting that the actual rates of infection are higher than publicly available data suggest. Further large-scale antibody testing is needed to determine the true prevalence of SARS-CoV-2 in the rural setting.

Pioglitazone improves superoxide dismutase mediated vascular reactivity in the obese Zucker rat.

OBJECTIVE: To test the hypothesis that the thiazolidinedione agent, pioglitazone, mediates its chronic BP lowering action via improving vascular reactivity. METHODS AND RESULTS: Lean (Fa/fa) and obese (fa/fa) Zucker rats were treated with or without pioglitazone (20 mg/ kg/day) for 4 weeks (n=8 animals per group). Pioglitazone treatment was associated with a significant improvement in oral glucose tolerance in the obese animals (p<0.05 compared with untreated obese). Pioglitazone prevented the development of hypertension seen in obese untreated rats (SBP 126+/-1 versus 138+/-1 mmHg; p<0.0001). Aortic ring preparations from pioglitazone-treated obese rats showed improved relaxation responsiveness (ED(50) 0.28 versus 1.15 U/ ml, p<0.001) to SOD, a NO potentiator, compared with untreated obese animals. CONCLUSIONS: SOD-mediated vasorelaxation may contribute to the chronic antihypertensive effect and/or the improvement in insulin sensitivity following pioglitazone treatment.