Sex-Specific Effects of Prenatal Stress on Memory and Markers of Neuronal Activity in Juvenile Rats

Stress during pregnancy can increase the incidence of emotional problems, learning and language difficulties in human infants and pre-adolescents. Most preclinical studies in rats that attempted to find experimental support for these observations were performed in adult male offspring, but the results are inconsistent. The aim of the current study was to examine the effect of prenatal stress on novel object recognition (NOR) and spatial learning and memory in the Morris water maze (MWM) of juvenile rats of both sexes. By the use of fluorescence immunohistochemistry and protein measurements by Western blot, we measured the expression of markers of neurogenesis (doublecortin, DCX) and neuronal activity that are important for synaptic plasticity and learning (c-fos, GluR1, nNOS). Since neuronal activity in the developing and adult brain can be regulated by astrocytes, we also measured the number of astrocytes and the expression of two astroglial proteins (GFAP and S100B) in the stress-responsive hippocampal dentate gyrus (DG). Experiments were performed on littermates of rats in which its effects on behavior were measured. We found for the first time that juvenile females performed better than males in the NOR and MWM tests. They also had higher densities of DCX and c-fos in the DG, together with the expression of nNOS and GluR1 in the subgranular zone (SGZ) of the DG. There were no sex differences in the expression of GFAP and S100B in astrocytes. Prenatal stress did not affect NOR in females, but improved it in males, together with an increase in DCX+ and c-fos, the number of GFAP-expressing astrocytes and the intensity of GFAP and S100B immunofluorescence in the DG. Staining intensity of GluR1 and nNOS in the hilus and SGZ of the DG, and protein expression in the whole DG, was unchanged in prenatally stressed males. Thus, prenatal stress changed the behavior and expression of key proteins in the DG to resemble that in females. A reduction in plasma testosterone, which although not attaining statistical significance was associated with that in anogenital distance, may contribute to the effect of prenatal stress in males. In females, prenatal stress had no effect on c-fos, DCX or the number of astrocytes but reduced the staining intensity of GluR1 and nNOS. Protein expression of nNOS was also significantly lower than that in prenatally stressed males. The differential effects of prenatal stress on hippocampal neuronal and glial markers may help to explain the sex-dependent effect on spatial learning in prepubertal rats.

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Fibroblast growth factor 8 overexpression is predictive of poor prognosis in pancreatic ductal adenocarcinoma

European Surgery ◽

10.1007/s10353-020-00669-6 ◽

2020 ◽

Vol 52 (6) ◽

pp. 282-289

Author(s):

Gerd Jomrich ◽

Lavinia Wilfing ◽

Sanja Radosavljevic ◽

Ario Parak ◽

Daniel Winkler ◽

...

Keyword(s):

Overall Survival ◽

Protein Expression ◽

Pancreatic Ductal Adenocarcinoma ◽

Statistical Significance ◽

Staining Intensity ◽

High Expression ◽

Ductal Adenocarcinoma ◽

Fibroblast Growth ◽

Eligibility Criteria ◽

Fibroblast Growth Factor 8

Summary Background Despite distinctive advances in the field of pancreatic cancer therapy over the past few years, patient survival remains poor. Fibroblast growth factors 8 (FGF8) and 18 (FGF18) both play a role in modulating the activity of malignant cells and have been identified as promising biomarkers in a number of cancers. However, no data exist on the expression of FGF8 and FGF18 in pancreatic ductal adenocarcinoma (PDAC). Methods Protein expression levels of FGF8 and FGF18 in postoperative specimens of neoadjuvantly treated and primarily resected patients were investigated using immunohistochemistry. Immunostaining scores were calculated as the products of the staining intensity and the staining rate. Scores exceeding the median score were considered as high expression. Results Specimens from 78 patients with PDAC were available and met the eligibility criteria for analysis of protein expression using immunohistochemistry. 15 (19.2%) patients had received neoadjuvant chemotherapy. High protein levels of FGF8 and FGF18 were detected in 40 (51.8%) and 33 (42.3%) patients, respectively. Kaplan–Meier analysis demonstrated significantly shorter overall survival in patients with high expression of FGF8 (p = 0.04). Multivariable Cox proportional hazard regression models revealed that high expression of FGF8 (Hazard ratio [HR] 0.53, 95% Confidence interval [CI] 0.32–0.89, p = 0.016) was an independent prognostic factor for diminished overall survival in patients with PDAC. By contrast, no statistical significance was found for FGF18 overexpression. In addition, the FGF8 protein level correlated with the factor resection margin (p = 0.042). Conclusion FGF8 is a promising target for new anticancer therapies using FGF inhibitors in pancreatic ductal adenocarcinomas.

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Inflammation in the Human Periodontium Induces Downregulation of the α1- and β1-Subunits of the sGC in Cementoclasts

International Journal of Molecular Sciences ◽

10.3390/ijms22020539 ◽

2021 ◽

Vol 22 (2) ◽

pp. 539

Author(s):

Yüksel Korkmaz ◽

Behrus Puladi ◽

Kerstin Galler ◽

Peer W. Kämmerer ◽

Agnes Schröder ◽

...

Keyword(s):

Protein Expression ◽

Alveolar Bone ◽

Soluble Guanylyl Cyclase ◽

Cathepsin K ◽

Staining Intensity ◽

Cyclic Guanosine Monophosphate ◽

Heme Iron ◽

Guanosine Monophosphate ◽

Independent Manner ◽

Periodontal Tissues

Nitric oxide (NO) binds to soluble guanylyl cyclase (sGC), activates it in a reduced oxidized heme iron state, and generates cyclic Guanosine Monophosphate (cGMP), which results in vasodilatation and inhibition of osteoclast activity. In inflammation, sGC is oxidized and becomes insensitive to NO. NO- and heme-independent activation of sGC requires protein expression of the α1- and β1-subunits. Inflammation of the periodontium induces the resorption of cementum by cementoclasts and the resorption of the alveolar bone by osteoclasts, which can lead to tooth loss. As the presence of sGC in cementoclasts is unknown, we investigated the α1- and β1-subunits of sGC in cementoclasts of healthy and inflamed human periodontium using double immunostaining for CD68 and cathepsin K and compared the findings with those of osteoclasts from the same sections. In comparison to cementoclasts in the healthy periodontium, cementoclasts under inflammatory conditions showed a decreased staining intensity for both α1- and β1-subunits of sGC, indicating reduced protein expression of these subunits. Therefore, pharmacological activation of sGC in inflamed periodontal tissues in an NO- and heme-independent manner could be considered as a new treatment strategy to inhibit cementum resorption.

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The clinical significance of glutathione peroxidase 2 in glioblastoma multiforme

Translational Neuroscience ◽

10.1515/tnsci-2021-0005 ◽

2021 ◽

Vol 12 (1) ◽

pp. 032-039

Author(s):

Bangming Guo ◽

Wenjuan Liao ◽

Shusheng Wang

Keyword(s):

Glioblastoma Multiforme ◽

Glutathione Peroxidase ◽

Mrna Expression ◽

Signaling Pathway ◽

Clinical Significance ◽

Cancer Cell ◽

Statistical Significance ◽

Adult Brain ◽

Chemokine Signaling ◽

Chemokine Signaling Pathway

Abstract Background Glioblastoma multiforme (GBM) is the leading cause of death among adult brain cancer patients. Glutathione peroxidase 2 (GPX2), as a factor in oxidative stress, plays an important role in carcinogenesis. However, its role in GBM has not been well established. The study aimed to investigate the clinical significance of GPX2 with GBM prognosis. Methods Data of GBM and healthy individuals were retrospectively collected from oncomine, cancer cell line encyclopedia (CCLE), gene expression profiling interactive analysis (GEPIA), UALCAN, and Human Protein Atlas. GPX2 mRNA expression was first assessed across various cancer types in oncomine and cancer cell lines from CCLE. The mRNA expression of GPX2 was compared between normal and GBM tissues using GEPIA (normal = 207; GBM = 163) and UALCAN (normal = 5; GBM = 156). The GPX2 methylation was analyzed using data from UALCAN (normal = 2; GBM = 140). The prognostic value of GPX2 in GBM was explored in GEPIA and UALCAN using Kaplan–Meier method. STRING database was used to construct protein–protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Statistical significance was set as <0.05. Results The current study revealed no significant differences in GPX2 expression between normal and GBM from GEPIA data (P > 0.05) and UALCAN (P = 0.257). Patients with higher GPX2 intended to have a poorer prognosis (P = 0.0089). The KEGG pathways found that chemokine-signaling pathway were the more preferred. Conclusions The findings demonstrated that GPX2 might be a potential diagnosis and prognostic indicator for GBM. Chemokine-signaling pathway may be involved in GPX2 function.

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Prenatal stress alters time characteristics and intensity of formalin-induced pain responses in juvenile rats

Brain Research ◽

10.1016/s0006-8993(01)02819-0 ◽

2001 ◽

Vol 915 (1) ◽

pp. 88-93 ◽

Cited By ~ 29

Author(s):

Irina Pavlovna Butkevich ◽

Elena Andreevna Vershinina

Keyword(s):

Prenatal Stress ◽

Juvenile Rats ◽

Pain Responses

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S1P modulator FTY720 limits matrix expansion in acute anti-thy1 mesangioproliferative glomerulonephritis

AJP Renal Physiology ◽

10.1152/ajprenal.00253.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. F1761-F1770 ◽

Cited By ~ 19

Author(s):

Sebastian Martini ◽

Stephanie Krämer ◽

Tanja Loof ◽

Yingrui Wang-Rosenke ◽

Ute Daig ◽

...

Keyword(s):

Protein Expression ◽

Blood Lymphocyte ◽

Matrix Protein ◽

Cell Injury ◽

Mesangial Cell ◽

Staining Intensity ◽

Beneficial Effects ◽

Collagen Iii ◽

Mesangioproliferative Glomerulonephritis ◽

Matrix Expansion

FTY720 is a novel immune modulator whose primary action is blood lymphocyte depletion through interaction with sphingosine-1-phosphate (S1P) receptors. The present study analyzes the effect of FTY720 on both the early mesangial cell injury and the subsequent matrix expansion phase of experimental mesangioproliferative glomerulonephritis. Disease was induced by injection of OX-7 anti-thy1 antibody into male Wistar rats. In both protocols, FTY720 administration (0.3 mg/kg body wt) resulted in a selective and very marked reduction in blood lymphocyte count. In the injury experiment, the S1P receptor modulator was given starting 5 days before and continued until 1 day after antibody injection. FTY720 did not significantly affect the degree of anti-thy1-induced mesangial cell lysis and glomerular-inducible nitric oxide production. In the matrix expansion experiment, FTY720 treatment was started 1 day after antibody injection and continued until day 7. In this protocol, the S1P modulator reduced proteinuria, histological matrix expansion, and glomerular protein expression of TGF-β1, fibronectin, and PAI-1. Glomerular collagen III staining intensity was decreased. FTY720 reduced markedly glomerular lymphocyte number per cross section and to a lesser degree macrophage infiltration. In conclusion, FTY720 significantly limits TGF-β1 overexpression and matrix protein expression following induction of acute anti-thy glomerulonephritis, involving reductions in blood and glomerular lymphocyte numbers. The results suggest that lymphocytes actively contribute to matrix expansion in experimental mesangioproliferative glomerulonephritis. Our study expands on findings on FTY720's beneficial effects on tubulointerstitial and functional disease progression previously reported in anti-thy1-induced chronic glomerulosclerosis.

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Effect of antigravity muscle activity on learning capacity and hippocampal protein expression in juvenile rats

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.616.11 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Yoshihiko Oke ◽

Fuminori Kawano ◽

Sachiko Nomura ◽

Takashi Ohira ◽

Ryo Fujita ◽

...

Keyword(s):

Protein Expression ◽

Muscle Activity ◽

Juvenile Rats ◽

Learning Capacity

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Hippocampal Protein Kinase C Gamma Signaling Mediates the Impairment of Spatial Learning and Memory in Prenatally Stressed Offspring Rats

Neuroscience ◽

10.1016/j.neuroscience.2019.06.030 ◽

2019 ◽

Vol 414 ◽

pp. 186-199 ◽

Cited By ~ 1

Author(s):

Qian Su ◽

Huiping Zhang ◽

Shaokang Dang ◽

Dan Yao ◽

Shuya Shao ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Learning And Memory ◽

Spatial Learning ◽

Spatial Learning And Memory ◽

Kinase C ◽

Protein Kinase C Gamma ◽

Prenatally Stressed

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Sleep-related c-Fos protein expression in the preoptic hypothalamus: effects of ambient warming

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.279.6.r2079 ◽

2000 ◽

Vol 279 (6) ◽

pp. R2079-R2088 ◽

Cited By ~ 84

Author(s):

Hui Gong ◽

Ronald Szymusiak ◽

Janice King ◽

Teresa Steininger ◽

Dennis McGinty

Keyword(s):

Protein Expression ◽

Ambient Temperature ◽

Neuronal Activity ◽

Preoptic Area ◽

Thermal Stimulation ◽

Preoptic Nucleus ◽

Ambient Temperatures ◽

Median Preoptic Nucleus ◽

Fos Protein ◽

Stimulation Of

Preoptic area (POA) neuronal activity promotes sleep, but the localization of critical sleep-active neurons is not completely known. Thermal stimulation of the POA also facilitates sleep. This study used the c-Fos protein immunostaining method to localize POA sleep-active neurons at control (22°C) and mildly elevated (31.5°C) ambient temperatures. At 22°C, after sleep, but not after waking, we found increased numbers of c-Fos immunoreactive neurons (IRNs) in both rostral and caudal parts of the median preoptic nucleus (MnPN) and in the ventrolateral preoptic area (VLPO). In animals sleeping at 31.5°C, significantly more Fos IRNs were found in the rostral MnPN compared with animals sleeping at 22°C. In VLPO, Fos IRN counts were no longer increased over waking levels after sleep at the elevated ambient temperature. Sleep-associated Fos IRNs were also found diffusely in the POA, but counts were lower than those made after waking. This study supports a hypothesis that the MnPN, as well as the VLPO, is part of the POA sleep-facilitating system and that the rostral MnPN may facilitate sleep, particularly at elevated ambient temperatures.

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