The cold-sensing ion channel TRPM8 regulates central and peripheral clockwork and the circadian oscillations of body temperature

Aim

Physiological functions in mammals show circadian oscillations, synchronized by daily cycles of light and temperature. Central and peripheral clocks participate in this regulation. Since the ion channel TRPM8 is a critical cold sensor, we investigated its role in circadian function.

Methods

We used TRPM8 reporter mouse lines and TRPM8-deficient mice. mRNA levels were determined by in situ hybridization or RT-qPCR and protein levels by immunofluorescence. A telemetry system was used to measure core body temperature (Tc).

Results

TRPM8 is expressed in the retina, specifically in cholinergic amacrine interneurons and in a subset of melanopsin-positive ganglion cells which project to the central pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. TRPM8-positive fibres were also found innervating choroid and ciliary body vasculature, with a putative function in intraocular temperature, as shown in TRPM8-deficient mice. Interestingly, Trpm8^−/− animals displayed increased expression of the clock gene Per2 and vasopressin (AVP) in the SCN, suggesting a regulatory role of TRPM8 on the central oscillator. Since SCN AVP neurons control body temperature, we studied Tc in driven and free-running conditions. TRPM8-deficiency increased the amplitude of Tc oscillations and, under dim constant light, induced a greater phase delay and instability of Tc rhythmicity. Finally, TRPM8-positive fibres innervate peripheral organs, like liver and white adipose tissue. Notably, Trpm8^−/− mice displayed a dysregulated expression of Per2 mRNA in these metabolic tissues.

Conclusion

Our findings support a function of TRPM8 as a temperature sensor involved in the regulation of central and peripheral clocks and the circadian control of Tc.     

Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats

Background/aim This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism, oxidative stress, NF-κB/Nrf2 pathways, and synaptic plasticity proteins in trained rats.Materials and methods Wistar rats were distributed into four groups: 1) control, 2) L/Zi: rats received L/Zi at the dose of 100 mg/kg by oral gavage, 3) exercise, 4) exercise+L/Zi: rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks. Results Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (p < 0.001). In the Exercise + L/Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-κB levels decreased (p <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (p < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group.Conclusion These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.     

Evaluation of systemic involvement of Coronavirus disease 2019 through spleen; size and texture analysis

Background/aimTo investigate the changes in the spleen size, parenchymal heterogeneity, and computed tomography (CT) texture analysis features of patients diagnosed with Coronavirus disease 2019 (COVID-19)Materials and methodsThe size and parenchymal structure of the spleen in 91 patients who underwent thoracic CT examination due to COVID-19 were evaluated. For the evaluation of parenchymal heterogeneity, CT texture analysis was performed using dedicated software (Olea Medical, France). The texture analysis of each case consisted of 15 first-order intensity-based features, 17 gray level co-occurrence matrix-based features, and 9 gray level run length matrix-based features.ResultsA total of 91 patients (45 males, 46 females) with a mean age of 54.31 ± 16.33 years (range: 18–81) were included in the study. A statistically significant decrease in spleen size was seen in the follow-up CT examinations (p < 0.001) whereas no statistically significant difference was found between the Hounsfield unit (HU) values. The radiomics consisted of first-order intensity-based features such as 90th percentile, maximum, interquartile range, range, mean absolute deviation, standard deviation, and variance, all of which showed statistically significant differences (p - values: < 0.001, < 0.001, 0.001, 0.003, 0.001, 0.001, and 0.004, respectively). “Correlation” as a gray level co-occurrence matrix-based feature and “gray level nonuniformity” as a gray level run length matrix-based feature showed statistically differences (p-values: 0.033 and < 0.001, respectively).ConclusionsAlthough COVID-19 manifests with lung involvement in the early stage, it can also cause systemic involvement, and the spleen may be one of its target organs. A decrease in the spleen size and parenchymal microstructure changes can be observed in the short follow-up time. It is hoped that the changes in the parenchymal microstructure will be demonstrated by a noninvasive method: texture analysis.     

Correlates of SARS-CoV-2 anti-RBD IgG antibody titers among persons experiencing homelessness in Los Angeles

Objectives

People experiencing homelessness (PEH) have been especially impacted by the COVID-19 pandemic, likely due to increased vulnerabilities stemming from chronic diseases, substance use, and mental health conditions.

Design

A case–control study to assess the presence of antibodies against SARS-CoV-2 among PEH and associations with key variables.

Sample

A convenience sample of 97 PEH in Skid Row, Los Angeles.

Measurements

A structured questionnaire assessing socio-demographic, mental health, drug and alcohol use, health care access, pandemic stress, and other COVID-19-specific questions.

Results

We found high anti-receptor binding domain (RBD) IgG titers among five of 15 PEH who reported no prior COVID-19 diagnosis or being vaccinated, suggesting undiagnosed and/or asymptomatic COVID-19. While anti-RBD IgG titers across vaccination categories were not statistically significant (p = .069), participants vaccinated with Janssen had the lowest mean anti-RBD IgG titers. In multivariable analysis, we found negative associations between level of SARS-CoV-2 antibody titers with the Janssen vaccine and depression; thus, a need for integrated care for PEH with depression and COVID-19.

Conclusions

Further research is warranted to confirm the immune response, initial and over time, to SARS-CoV-2 infection and to COVID-19 vaccinations, particularly among PEH whose immune systems may be impacted by multiple health conditions.