scholarly journals Adenosine Kinase Expression in the Frontal Cortex in Schizophrenia

2019 ◽  
Vol 46 (3) ◽  
pp. 690-698
Author(s):  
Cassidy L Moody ◽  
Adam J Funk ◽  
Emily Devine ◽  
Ryan C Devore Homan ◽  
Detlev Boison ◽  
...  

Abstract The adenosine hypothesis of schizophrenia posits that reduced availability of the neuromodulator adenosine contributes to dysregulation of dopamine and glutamate transmission and the symptoms associated with schizophrenia. It has been proposed that increased expression of the enzyme adenosine kinase (ADK) may drive hypofunction of the adenosine system. While animal models of ADK overexpression support such a role for altered ADK, the expression of ADK in schizophrenia has yet to be examined. In this study, we assayed ADK gene and protein expression in frontocortical tissue from schizophrenia subjects. In the dorsolateral prefrontal cortex (DLPFC), ADK-long and -short splice variant expression was not significantly altered in schizophrenia compared to controls. There was also no significant difference in ADK splice variant expression in the frontal cortex of rats treated chronically with haloperidol-decanoate, in a study to identify the effect of antipsychotics on ADK gene expression. ADK protein expression was not significantly altered in the DLPFC or anterior cingulate cortex (ACC). There was no significant effect of antipsychotic medication on ADK protein expression in the DLPFC or ACC. Overall, our results suggest that increased ADK expression does not contribute to hypofunction of the adenosine system in schizophrenia and that alternative mechanisms are involved in dysregulation of this system in schizophrenia.

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Hanlin Tang ◽  
Hsiang-Yu Yu ◽  
Chien-Chen Chou ◽  
Nathan E Crone ◽  
Joseph R Madsen ◽  
...  

Rapid and flexible interpretation of conflicting sensory inputs in the context of current goals is a critical component of cognitive control that is orchestrated by frontal cortex. The relative roles of distinct subregions within frontal cortex are poorly understood. To examine the dynamics underlying cognitive control across frontal regions, we took advantage of the spatiotemporal resolution of intracranial recordings in epilepsy patients while subjects resolved color-word conflict. We observed differential activity preceding the behavioral responses to conflict trials throughout frontal cortex; this activity was correlated with behavioral reaction times. These signals emerged first in anterior cingulate cortex (ACC) before dorsolateral prefrontal cortex (dlPFC), followed by medial frontal cortex (mFC) and then by orbitofrontal cortex (OFC). These results disassociate the frontal subregions based on their dynamics, and suggest a temporal hierarchy for cognitive control in human cortex.


2009 ◽  
Vol 21 (1) ◽  
pp. 207
Author(s):  
M. Sakatani ◽  
K. Yamanaka ◽  
M. Takahashi

In a previous study, we reported that 8-cell-stage embryos exposed to a temperature of 41°C for 6 h had significantly increased embryonic mortality and intracellular reactive oxygen species (ROS). There have been some reports that ROS regulates the expression of genes encoding antioxidant enzymes in culture cells. In this study, we investigated the gene and protein expression of antioxidant enzymes in bovine 8-cell-stage embryos exposed to heat shock. In vitro-produced bovine embryos were used for the experiment. Embryos were cultured with CR1aa + 5% FCS at 38.5°C in 5% CO2 and 5% O2. On Day 2 after fertilization, 8-cell-stage embryos were exposed to heat shock at 41°C in 5% CO2 and 5% O2 for 6 h (HS). Eight-cell-stage embryos cultured at 38.5°C in 5% CO2 and 5% O2 were sampled at the same collection time as controls. After HS, 20 embryos were immediately collected for gene expression analysis. Expression of heat shock protein 70 (HSP70), CuZn-containing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxide (GPx) genes was examined by real-time polymerase chain reaction. Twenty embryos were also collected after 3 h of HS (3 h) and at 18 h after HS (18 h) to evaluate the expression of proteins. Expression of HSP70, SOD, and CAT proteins was examined by Western blotting. Both the gene and protein expression levels of HS groups were normalized to those of the controls to obtain the relative expression levels. All results were analyzed by Student’s t-test. Expression of the HSP70 gene significantly increased in HS embryos (P < 0.05). Expression of the SOD and CAT genes tended to increase in HS embryos (P < 0.07), but there were no significant differences in expression of the GPx gene. There was no significant difference in protein expression in all the antioxidant enzymes in 3-h-sampled embryos. Expression of the HSP70 protein increased significantly in heat-shocked embryos sampled at 18 h (P < 0.05). These results indicate that expression of antioxidant enzymes was not greatly affected in 8-cell-stage embryos exposed to HS. Thus, these results suggest the possibility that the early-stage embryos were stressed and damaged from heat shock because of their poor antioxidative potency. Table 1.Gene and protein expression of embryos This work was supported by KAKENHI [16780209, Grant-in-Aid for Young Scientists (B)].


2018 ◽  
Vol 46 (5) ◽  
pp. 2149-2164 ◽  
Author(s):  
Hua Guan ◽  
Yali Zhang ◽  
Shoucui Gao ◽  
Liang Bai ◽  
Sihai Zhao ◽  
...  

Background/Aims: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that acts as soluble modulators of Wnt signaling. Given the substantial rise in obesity, depot-specific fat accumulation and its associated diseases like diabetes, it is important to understand the molecular basis of depot-specific adipocyte differentiation. In the current study, we investigated the expression of SFRP4 in both subcutaneous and visceral adipose tissue in terms of their differentiation. Methods: White preadipocytes were isolated from the inguinal white adipose tissue (iWAT) and epididymal white adipose tissue (eWAT) from C57BL/6J mice (age: 8-week-old, male). SFRP4 expression in iWAT and eWAT preadipocytes was silenced by siRNA transfection and harvested cells for gene and protein expression analysis was performed during the differentiation. Furthermore, iWAT and eWAT preadipocytes treated with or without IL-1β were harvested for gene and protein expression analysis. Results: SFRP4 expression levels were gradually increased and proportionally associated with eWAT adipocyte differentiation toward maturation at 14 days, while iWAT adipocyte just showed an opposite tendency. Moreover, genetic (adiponectin, C/EBPα, C/EBPβ, FABP4, GLUT4 and PPARγ) analysis demonstrated that depot-specific adipogenesis in response to SFRP4 silencing in eWAT and iWAT preadipocytes. Upon IL-1β treatment, SFRP4 mRNA expression decreased significantly in iWAT adipocyte, but the expression was no significant difference in eWAT adipocyte. Conclusion: These results suggest that SFRP4 expression differentially mediates adipocyte differentiation and may play an important role in adipogenesis.


2018 ◽  
Vol 15 (3) ◽  
pp. 796-806 ◽  
Author(s):  
María S. García-Gutiérrez ◽  
Francisco Navarrete ◽  
Gemma Navarro ◽  
Irene Reyes-Resina ◽  
Rafael Franco ◽  
...  

2019 ◽  
Vol 16 (11) ◽  
pp. 1063-1071 ◽  
Author(s):  
Gonzague Foucault ◽  
Guillaume T Duval ◽  
Romain Simon ◽  
Olivier Beauchet ◽  
Mickael Dinomais ◽  
...  

Background: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults. Method: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables. Results: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (β=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021). Conclusion: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.


2018 ◽  
Vol 18 (7) ◽  
pp. 1025-1031
Author(s):  
Cheng Luo ◽  
Di Wu ◽  
Meiling Chen ◽  
Wenhua Miao ◽  
Changfeng Xue ◽  
...  

Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined. Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy. Results: ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation. Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly


Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 906
Author(s):  
Agnieszka Mikłosz ◽  
Bartłomiej Łukaszuk ◽  
Adrian Chabowski ◽  
Jan Górski

Endothelial lipase (EL) is an enzyme capable of HDL phospholipids hydrolysis. Its action leads to a reduction in the serum high-density lipoprotein concentration, and thus, it exerts a pro-atherogenic effect. This study examines the impact of a single bout exercise on the gene and protein expression of the EL in skeletal muscles composed of different fiber types (the soleus—mainly type I, the red gastrocnemius—mostly IIA, and the white gastrocnemius—predominantly IIX fibers), as well as the diaphragm, and the heart. Wistar rats were subjected to a treadmill run: 1) t = 30 [min], V = 18 [m/min]; 2) t = 30 [min], V = 28 [m/min]; 3) t = 120 [min], V = 18 [m/min] (designated: M30, F30, and M120, respectively). We established EL expression in the total muscle homogenates in sedentary animals. Resting values could be ordered with the decreasing EL protein expression as follows: endothelium of left ventricle > diaphragm > red gastrocnemius > right ventricle > soleus > white gastrocnemius. Furthermore, we observed that even a single bout of exercise was capable of inducing changes in the mRNA and protein level of EL, with a clearer pattern observed for the former. After 30 min of running at either exercise intensity, the expression of EL transcript in all the cardiovascular components of muscles tested, except the soleus, was reduced in comparison to the respective sedentary control. The protein content of EL varied with the intensity and/or duration of the run in the studied whole tissue homogenates. The observed differences between EL expression in vascular beds of muscles may indicate the muscle-specific role of the lipase.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Matthew Mannarino ◽  
Hosni Cherif ◽  
Li Li ◽  
Kai Sheng ◽  
Oded Rabau ◽  
...  

Abstract Background There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. Methods Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). Results An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. Conclusions Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.


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