scholarly journals Is there a link between TNF gene expression and cognitive deficits in depression?

1970 ◽  
Vol 64 (1) ◽  
Author(s):  
Kinga Bobińska ◽  
Elżbieta Gałecka ◽  
Janusz Szemraj ◽  
Piotr Gałecki ◽  
Monika Talarowska

Neuroinflammation is a known factor in the pathogenesis of recurrent depressive disorders. Depression is accompanied by activated immune-inflammatory pathways including increased levels of TNFα, sTNFR1and sTNFR2.The purpose of this study was to analyse the TNF-α, TNFRSF1A and TNFRSF1B genes on both mRNA and protein levels in patients with rDD, and to investigate the relationship between TNF-α,TNFRSF1A and TNFRSF1B gene expression and cognitive performance. The study comprised 158 subjects: patients with recurrent depressive disorder (n=89) and healthy subjects (n=69). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Both mRNA and protein expression levels of all genes were significantly higher in rDD subjects when compared to healthy controls. No statistically significant correlations were observed between the analysed variables in both the rDD group and the HS test group. The only exception was noticed in the HS test group, where increased expression of TNFRSF1A and TNFRSF1B gene negatively affected the performance of the AVLT test. However, statistically significant correlations between TNF, TNFRSF1A, TNFRSF1B mRNA gene expression levels and all the neuropsychological tests used in the survey for the entire group were observed. 1.The results of our study show increased expression of the TNF, TNFRSF1A and TNFRSF1B genes on both mRNA and protein levels in depression. 2. Elevated expression of TNF-α, TNFRSF1A and TNFRSF1B negatively correlates with cognitive efficiency: working memory, executive functions, attention, auditory-verbal memory, effectiveness of learning processes and verbal fluency.

2006 ◽  
Vol 14 (7S_Part_17) ◽  
pp. P923-P924
Author(s):  
Emilie Thomas ◽  
Tharick A. Pascoal ◽  
Melissa Savard ◽  
Laurie-Anne Dion ◽  
Mira Chamoun ◽  
...  

2020 ◽  
Vol 35 (6) ◽  
pp. 1045-1045
Author(s):  
Leonard S ◽  
Olsen E ◽  
Bradbury K

Abstract Objective Anterior temporal lobectomy (ATL) surgery for epilepsy is commonly associated with post-surgical impairments in memory and language abilities, specifically episodic memory and confrontational naming. Less is known regarding outcomes of patients with atypical language dominance. Method Casey is a 19 year-old, ambidextrous, male with a history of remote symptomatic medically intractable focal epilepsy secondary to right inferior temporal encephalomalacia. Casey underwent right anterior temporal lobectomy and resection of mesial structures including part of the hippocampus. Results Casey’s pre-surgical neuropsychological evaluation revealed overall intellectual functioning in the average range with relative strengths in perceptual reasoning skills and weaknesses in attention, executive control, confrontational naming, and verbal fluency. Casey’s pre-surgical cognitive profile and functional MRI were suggestive of bilateral language organization. At post-surgical evaluation, Casey demonstrated strong overall cognitive abilities, basic reading, visual–spatial skills, and visual memory, as well as notable improvements in his processing speed and visual-motor integration. He demonstrated significant improvement in verbal working memory, verbal fluency, and contextual verbal memory. Casey continued to show significant weaknesses in word finding, phonetic verbal fluency, and rote verbal learning and memory, and milder weaknesses in aspects of executive functioning. Casey continued to demonstrate mood difficulties. Conclusions The current case provides evidence of continued mild deficits in traditional dominant hemisphere skills including rote verbal memory and focal language abilities, in a patient with a history of mixed language dominance, following right hemisphere ATL surgery. This case further highlights the importance of pre-surgical neuropsychological evaluation and fMRI in patients undergoing right ATL surgery.


2016 ◽  
Vol 28 (4) ◽  
pp. 221-231 ◽  
Author(s):  
Kinga Bobińska ◽  
Janusz Szemraj ◽  
Piotr Gałecki ◽  
Monika Talarowska

ObjectiveAmong the 28 metalloproteinases described so far, 23 can be found in the human organism, but only few are expressed in the human brain. The main objective of this study was to analyse the relationship between MMP-2, MMP-9 and TIMP-2 gene expression and cognitive performance.MethodsThe study comprised 234 subjects: patients suffering from recurrent depressive disorder (rDD, n=139) and healthy subjects (HS, n=95). The cognitive function assessment was carried out with the help of the following tests: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Gene expression on the mRNA and protein level was evaluated for MMP-2, MMP-9 and TIMP-2 in both groups using RNA extraction, reverse transcription and enzyme-linked immunosorbent assay.ResultsBoth mRNA and protein expression levels of all the genes were significantly lower in rDD subjects as compared with HS. Having analysed the entire experimental group (N=234), significant interrelations were found between the expression of the analysed genes and the results of the tests used to measure cognitive functions. Increased expression on both the mRNA and the protein level was associated in each case with better performance of all the tests conducted. After carrying out a separate analysis on the people from the rDD group and the HS group, similar dependencies were still observed.ConclusionsThe results of our study show decreased expression of MMP-2, MMP-9 and TIMP-2 genes on both mRNA and protein levels in depression. Elevated expression of MMP-2, MMP-9, TIMP-2 positively affects cognitive efficiency: working memory, executive functions, attention functions, direct and delayed auditory–verbal memory, the effectiveness of learning processes and verbal fluency. The study highlights the important role of peripheral matrix metalloproteinases genes in depression and cognitive functions.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Li ◽  
Siyuan Li ◽  
Ying Hu ◽  
Guolei Cao ◽  
Siyao Wang ◽  
...  

Objective. We investigated the expression levels of both FOSL2 mRNA and protein as well as evaluating DNA methylation in the blood of type 2 diabetes mellitus (T2DM) Uyghur patients from Xinjiang. This study also evaluated whether FOSL2 gene expression had demonstrated any associations with clinical and biochemical indicators of T2DM. Methods. One hundred Uyghur subjects where divided into two groups, T2DM and nonimpaired glucose tolerance (NGT) groups. DNA methylation of FOSL2 was also analyzed by MassARRAY Spectrometry and methylation data of individual units were generated by the EpiTyper v1.0.5 software. The expression levels of FOS-like antigen 2 (FOSL2) and the protein expression levels were analyzed. Results. Significant differences were observed in mRNA and protein levels when compared with the NGT group, while methylation rates of eight CpG units within the FOSL2 gene were higher in the T2DM group. Methylation of CpG sites was found to inversely correlate with expression of other markers. Conclusions. Results show that a correlation between mRNA, protein, and DNA methylation of FOSL2 gene exists among T2DM patients from Uyghur. FOSL2 protein and mRNA were downregulated and the DNA became hypermethylated, all of which may be involved in T2DM pathogenesis in this population.


2018 ◽  
Vol 19 (7) ◽  
pp. 2008 ◽  
Author(s):  
Yurina Kashino ◽  
Yutaro Obara ◽  
Yosuke Okamoto ◽  
Takeo Saneyoshi ◽  
Yasunori Hayashi ◽  
...  

Extracellular signal-regulated kinase 5 (ERK5) regulates diverse physiological responses such as proliferation, differentiation, and gene expression. Previously, we demonstrated that ERK5 is essential for neurite outgrowth and catecholamine biosynthesis in PC12 cells and sympathetic neurons. However, it remains unclear how ERK5 regulates the activity of ion channels, which are important for membrane excitability. Thus, we examined the effect of ERK5 on the ion channel activity in the PC12 cells that overexpress both ERK5 and the constitutively active MEK5 mutant. The gene and protein expression levels of voltage-dependent Ca2+ and K+ channels were determined by RT-qPCR or Western blotting. The A-type K+ current was recorded using the whole-cell patch clamp method. In these ERK5-activated cells, the gene expression levels of voltage-dependent L- and P/Q-type Ca2+ channels did not alter, but the N-type Ca2+ channel was slightly reduced. In contrast, those of Kv4.2 and Kv4.3, which are components of the A-type current, were significantly enhanced. Unexpectedly, the protein levels of Kv4.2 were not elevated by ERK5 activation, but the phosphorylation levels were increased by ERK5 activation. By electrophysiological analysis, the inactivation time constant of the A-type current was prolonged by ERK5 activation, without changes in the peak current. Taken together, ERK5 inhibits an inactivation of the A-type current by phosphorylation of Kv4.2, which may contribute to the neuronal differentiation process.


2020 ◽  
Vol 24 (3) ◽  
Author(s):  
Nazila Payandeh ◽  
Maghsoud Peeri ◽  
Mohammad Ali Azarbayjani ◽  
Seyed Ali Hosseini

Background: A healthy lifestyle, nutrition, and exercise can improve bone mass via several mechanisms. Objectives: This study assessed the effects of four weeks of palm pollen consumption along with resistance training on protein and gene expression levels of Runt-related transcription factor 2 (Runx2) in bone tissue of rats. Methods: Thirty-six rats were selected and assigned into six groups, including (1) training + testosterone, (2) training + palm pollen, (3) testosterone, (4) palm pollen, (5) training and (6) sham. Then, 100 mg/kg of palm pollen was prescribed five days per week. Resistance training was performed five sessions per week, and 2 mg/kg of testosterone propionate was prescribed peritoneally. Gene expression and protein levels of Runx2 were measured via the real-time PCR and Western blot methods. Results: Training had a significant effect on the increase in Runx2 protein levels (P ≤ 0.05). Training + testosterone, training + palm pollen, testosterone, and palm pollen had significant effects on gene expression and protein levels of Runx2 (P ≤ 0.05). Training + testosterone and training + palm pollen had more favorable effects on the increase of gene expression and protein levels of Runx2 than had testosterone, palm pollen, and training (P ≤ 0.05). Conclusions: Although training, palm pollen, and testosterone alone could increase the Runx2 protein levels in the bone tissue of rats, training with palm pollen and training with testosterone appeared to have more favorable effects on the increase of gene expression and protein levels of Runx2 than either alone.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3977-3977
Author(s):  
Ida Bruun Kristensen ◽  
Jacob Haaber ◽  
Maria B Lyng ◽  
Lise Pedersen ◽  
Lars Melholt Rasmussen ◽  
...  

Abstract Abstract 3977 Osteolytic bone disease (OBD) in multiple myeloma (MM) is known to be caused by a combination of osteoclast hyperactivation and osteoblast inhibition. One of the pathways known to be involved in osteoblast inhibition from in vitro studies is the HGF pathway consisting of HGF, its receptor MET, the co-receptor Syndecan-1 (SDC-1), the partial MET antagonist Decorin and HGF activator responsible for HGF processing to its active form. So far, gene expression studies in MM have been performed on isolated MM plasma cells or bone marrow (BM) aspirates, which are not completely representative of the cell composition in the BM micro-environment. We used a novel strategy, whereby gene expression of factors associated with the HGF pathway was evaluated in snap-frozen BM biopsies, and moreover we determined the protein levels in matched BM plasma samples. An additional BM core biopsy obtained during the diagnostic procedure of MM patients was snap-frozen. Biopsies were cut, homogenized and RNA was purified and analyzed by qRT-PCR using low density arrays (Applied Biosystems). The relative quantitative gene expression was calculated using 3 internal reference genes (ABL, GAPDH and GUS). OBD was evaluated using standard radiographs. All patients were untreated and did not receive medicine that could influence bone remodeling. We examined 10 healthy volunteers (HV), 35 monoclonal gammopathy of unknown significance (MGUS) and 65 untreated MM patients, which according to radiographic findings were divided into NO/LOW and advanced OBD, i.e. OBD in ≥2 regions. ELISA was performed on a total of 31 matched BM plasma samples of HV, MGUS and MM obtained at the same time point as the biopsies. In addition, extra samples without gene data (N=52) were analyzed. Commercial kits for SDC-1 (Diaclone), HGF (RnD, Quantikine) and Decorin (RnD, Duoset) were run in duplicates according to manufacturer's instructions. Gene expression of HGF, SDC1, and MET were significantly different comparing HV, MGUS, no/low and advanced OBD (p<0.05) (For HGF, see figure 1). Decorin was not associated to OBD. HGF activator was not expressed in any of our samples, but only in the positive control. A significant correlation between gene and protein expression levels measured by ELISA was found for SDC-1 (Spearman's rho= 0.463, p=0.0058) and HGF (Spearman's rho=0.45, p=0.01). No correlation was found between Decorin gene levels and BM plasma levels (Spearman's rho =-0.24, p=0.22). The protein level of SDC-1 and HGF in BM plasma were both upregulated in MM and associated significantly to OBD level (p<0.05), while Decorin were significantly downregulated in MGUS and MM samples compared to HVs (p<0.05). A significant difference in HGF BM plasma levels were found between patients with no/limited OBD (median: 1.7ng/mL) and advanced OBD (median: 6.2ng/mL) in BM plasma. In our expression study reflecting the in vivo situation in MM patients, genes in the HGF pathway and proteins were significantly associated to OBD. The use of whole snap-frozen BM biopsies is a novel strategy for evaluation of gene expression in MM making it possible to investigate patients independent of degree of MM plasma cell infiltration. In addition to the dys-regulated gene expression levels alteration of SDC-1 and HGF was also observed at protein level, supporting the gene expression findings, and underscoring the usefulness of BM biopsies for gene expression studies in MM. Furthermore, our study for the first time shows up regulation of HGF in association with OBD at both gene and protein level in a large clinical material. Figure 1A. HGF Gene Expression levels in whole snap-frozen BM biopsies. Figure 1B. HGF protein levels in BM plasma (pg/mL). 1 = HV, 2 = MGUS, 3 = no/low OBD MM, 4 = advanced OBD MM. Figure 1A. HGF Gene Expression levels in whole snap-frozen BM biopsies. Figure 1B. HGF protein levels in BM plasma (pg/mL). 1 = HV, 2 = MGUS, 3 = no/low OBD MM, 4 = advanced OBD MM. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 41 (10) ◽  
pp. 2131-2139 ◽  
Author(s):  
A. Hofer ◽  
T. Bodner ◽  
A. Kaufmann ◽  
G. Kemmler ◽  
U. Mattarei ◽  
...  

BackgroundA cross-sectional study was conducted in participants with schizophrenia to explore a potential association between the patients' remission status and neurocognitive functioning and to examine whether these factors have an impact on functional outcome.MethodPsychopathological symptoms were rated by means of the Positive and Negative Syndrome Scale with symptom remission being assessed by applying the severity component of the recently proposed remission criteria. Tests for the cognitive battery were selected to cover domains known to be impaired in patients with schizophrenia. Next to pre-morbid intelligence, attention performance, executive functioning, verbal fluency, verbal learning and memory, working memory and visual memory were assessed. The joint effect of remission status and neurocognitive functioning on treatment outcome was investigated by logistic regression analysis.ResultsOut of 140 patients included in the study, 62 were symptomatically remitted. Mean age, education and sex distribution were comparable in remitted and non-remitted patients. Remitted patients showed significantly higher values on tests of verbal fluency, alertness and optical vigilance. Both symptomatic remission as well as performance on tests of working memory and verbal memory had a significant effect on the patients' employment status.ConclusionsIn the present study neuropsychological measures of frontal lobe functioning were associated with symptomatic remission from schizophrenia. In addition, both symptomatic remission and performance on tests of working memory and verbal memory had a significant effect on the patients' employment status. Longitudinal follow-up data are needed to determine how the associations of these determinants of functional outcome interact and change over time.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1128 ◽  
Author(s):  
David S. Moura ◽  
Paloma Sanchez-Bustos ◽  
Antonio Fernandez-Serra ◽  
María Lopez-Alvarez ◽  
José L. Mondaza-Hernandez ◽  
...  

A translational study was designed to analyze the expression of nucleotide excision repair (NER) and homologous recombination (HR) genes as potential predictive biomarkers for trabectedin in soft-tissue sarcoma (STS). This study is part of a randomized phase II trial comparing trabectedin plus doxorubicin versus doxorubicin in advanced STS. Gene expression levels were evaluated by qRT-PCR, while CUL4A protein levels were quantified by immunohistochemistry. Expression levels were correlated with patients’ progression-free survival (PFS) and overall survival (OS). Gene expression was also evaluated in cell lines and correlated with trabectedin sensitivity. In doxorubicin arm and in the whole series, which includes samples from both arms, no significant differences in terms of PFS were observed amongst the analyzed genes. In the group treated with trabectedin plus doxorubicin, the median of PFS was significantly longer in cases with CUL4A, ERCC1, or ERCC5 overexpression, while BRCA1 expression did not correlated with PFS. Gene expression had no prognostic influence in OS. CUL4A protein levels correlated with worse PFS in doxorubicin arm and in the whole series. In cell lines, only overexpression of ERCC1 was significantly correlated with trabectedin sensitivity. In conclusion, CUL4A, ERCC5, and mainly ERCC1 acted as predictive factors for trabectedin efficacy in advanced STS.


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