RESUMEN
Schizophrenia is a clinically and genetically heterogeneous disorder of unknown etiology. PDLIM5 variants have been linked to schizophrenia and other related neuropsychiatric disorders and upregulated in the brain of schizophrenia patients suggesting a possible pathogenic role in disease progression. The aim of this study is to examine the potential association of schizophrenia in Emirati patients with previously reported variants in PDLIM5, PICK1, NRG3 or DISC1 genes. Consequently, we found a secondary association between PDLIM5 variants and the paranoid subtype of schizophrenia in Emirati Arabs suggesting that PDLIM5 may represent a determinate/marker for schizophrenia subtype specification. However, no associations were found with variants in PICK1, NRG3 or DISC1 genes.
RESUMEN
We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4-10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤ 2-week-old C57BL/6 mice following RSV infection. Mice (5-14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1-10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1-10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O2 consumption) and ATP following RSV infection is independent of either age or genetic background of the host.
Asunto(s)
Metabolismo Energético , Pulmón/fisiopatología , Pulmón/virología , Infecciones por Virus Sincitial Respiratorio/fisiopatología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/fisiología , Adenosina Trifosfato/biosíntesis , Animales , Animales Recién Nacidos , Histocitoquímica , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica , Consumo de OxígenoRESUMEN
BACKGROUND: This study aimed to establish a suitable in vitro system for investigating effects of respiratory pathogens and toxins on lung tissue bioenergetics (cellular respiration and ATP content) and caspase activity. Wistar rats and C57Bl/6 mice were anesthetized by sevoflurane inhalation. Lung fragments were then collected and incubated at 37°C in a continuously gassed (with 95% O2:5% CO2) Minimal Essential Medium (MEM) or Krebs-Henseleit buffer. Phosphorescence O2 analyzer that measured dissolved O2 concentration as a function of time was used to monitor the rate of cellular mitochondrial O2 consumption. Cellular ATP content was measured using the luciferin/luciferase system. The caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin (Ac-DEVD-AMC) was used to monitor intracellular caspase activity; cleaved AMC moieties (reflecting caspase activity) were separated on HPLC and detected by fluorescence. Lung histology and immunostaining with anti-cleaved caspase-3 antibody were also performed. RESULTS: For Wistar rats, the values of kc and ATP for 0 < t ≤ 7 h (mean ± SD) were 0.15 ± 0.02 µM O2 min-1 mg-1 (n = 18, coefficient of variation, Cv = 13%) and 131 ± 69 pmol mg-1 (n = 16, Cv = 53%), respectively. The AMC peak areas remained relatively small despite a ~5-fold rise over 6 h. Good tissue preservation was evident despite time-dependent increases in apoptotic cells. Lung tissue bioenergetics, caspase activity and structure were deleterious in unoxygenated or intermittently oxygenated solutions. Incubating lung tissue in O2 depleted MEM for 30 min or anesthesia by urethane had no effect on lung bioenergetics, but produced higher caspase activity. CONCLUSIONS: Lung tissue bioenergetics and structure could be maintained in vitro in oxygenated buffer for several hours and, thus, used as biomarkers for investigating respiratory pathogens or toxins.