RESUMO
Objective: To investigate the effects of PM2.5 exposure at different stages of early life on the prefrontal cortex of offspring rats. Methods: Twelve pregnant SD rats were randomly divided into four groups: Control group (CG), Maternal pregnancy exposure group (MG), Early postnatal exposure group (EP) and Perinatal period exposure group (PP), 3 rats in each group. The pregnant and offspring rats were exposed to clean air or 8-fold concentrated PM2.5. MG was exposed from gestational day (GD) 1 to GD21. EP was exposed from postnatal day (PND) 1 to PND21, and PP was exposed from GD1 to PND21. After exposure, the prefrontal cortex of 6 offspring rats in each group was analyzed. HE staining was used to observe the pathological damage in the prefrontal cortex. ELISA was employed to detect neuroinflammatory factors, and HPLC/MSC was applied to determine neurotransmitter content. Western blot and colorimetry were applied for detecting astrocyte markers and oxidative stress markers, respectively. Results: Compared with MG and CG, the pathological changes of prefrontal cortex in PP and EP were more obvious. Compared with MG and CG, the neuroinflammatory factors (IL-1, IL-6, TNF-α) in PP and EP were increased significantly (P<0.01), the level of MT were decreased significantly (P<0.05), and the level of oxytocin (OT) showed a downward trend; the level of neurotransmitter ACh was also increased significantly (P<0.01). Compared with MG and CG, the GFAP level of PP and EP showed an upward trend, the level of oxidative stress index SOD in PP and EP was decreased significantly (P<0.01), and the level of ROS was increased significantly (P<0.01). Compared with the offspring rats of CG and MG, the CAT level of PP was decreased significantly (P<0.01, P<0.05). Compared with the offspring rats of CG, the CAT level of EP was decreased significantly (P<0.05). There was no significant difference in IL-1, IL-6, TNF-α, MT, OT, ACh, GFAP, SOD, ROS and CAT levels between PP and EP, or MG and CG. Conclusion: PM2.5 exposure in early life has adverse effects on the prefrontal cortex of offspring male rats, and early birth exposure may be more sensitive.
Assuntos
Animais , Feminino , Masculino , Gravidez , Ratos , Interleucina-1/farmacologia , Interleucina-6 , Neurotransmissores , Material Particulado/toxicidade , Córtex Pré-Frontal , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Superóxido Dismutase , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND@#Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level.@*METHODS@#We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses.@*RESULTS@#The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance.@*CONCLUSION@#Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.
Assuntos
Animais , Humanos , Estimulação Encefálica Profunda , Epilepsia do Lobo Temporal/terapia , Hipocampo , Macaca , ConvulsõesRESUMO
<p><b>OBJECTIVE</b>To investigate the association of filaggrin gene (FLG) polymorphism with atopic dermatitis (AD) in southern Chinese Han population.</p><p><b>METHODS</b>The frequencies of the 13 known FLG gene single nucleotide polymorphism(SNPs), including 3321delA, 441delA, 1249insG, E1795X, S3296X, R501X, 2282del4, R2447X, S2889X, 7945delA, 3702delG, Q2417X, R4307X, were detected in a cohort of 50 AD patients and 100 control individuals using polymerase chain reaction (PCR) and DNA sequencing.</p><p><b>RESULTS</b>FLG 3321delA and 441delA were detected in 14 (28%) and 6 (12%) AD patients, respectively. The other 11 SNPs were not detected in the patients. None of the 13 SNPs was detected in the controls.</p><p><b>CONCLUSION</b>The results suggested that the FLG gene might be associated with atopic dermatitis susceptibility in southern Chinese Han population.</p>