scholarly journals Identification of functional features underlying heat stress response in Sprague-Dawley rats using mixed linear models

Author(s):  
Krzysztof Kotlarz ◽  
Magda Mielczarek ◽  
Yachun Wang ◽  
Jinhuan Dou ◽  
Tomasz Suchocki ◽  
...  

Abstract Since global temperature is expected to rise by 2℃ in 2050 heat stress may become the most severe environmental factor. In the study, we illustrate the application of mixed linear models for the analysis of whole transcriptome expression in livers and adrenal tissues of Sprague-Dawley rats obtained by a heat stress experiment. By applying those models, we considered four sources of variation in transcript expression, comprising transcripts (1), genes (2), Gene Ontology terms (3), and Reactome pathways (4) and focussed on accounting for the similarity within each source, which was expressed as a covariance matrix. Models based on transcripts or genes levels explained a larger proportion of log2 fold change than models fitting the functional components of Gene Ontology terms or Reactome pathways. In the liver, among the most significant genes were PNKD and TRIP12. In the adrenal tissue, one transcript of the SUCO gene was expressed more strongly in the control group than in the heat-stress group. PLEC had two transcripts, which were significantly overexpressed in the heat-stress group. PER3 was significant only on gene level. Moving to the functional scale, five Gene Ontologies and one Reactome pathway were significant in the liver. They can be grouped into ontologies related to DNA repair, histone ubiquitination, the regulation of embryonic development and cytoplasmic translation. Linear mixed models are valuable tools for the analysis of high-throughput biological data. Their main advantages are the possibility to incorporate information on covariance between observations and circumventing the problem of multiple testing.

2019 ◽  
Vol 81 ◽  
pp. 12-19 ◽  
Author(s):  
Jinhuan Dou ◽  
Yuri R. Montanholi ◽  
Zezhao Wang ◽  
Zhongshu Li ◽  
Ying Yu ◽  
...  

Molecules ◽  
2015 ◽  
Vol 20 (11) ◽  
pp. 20240-20253 ◽  
Author(s):  
Kui-Jin Kim ◽  
Kye-Yoon Yoon ◽  
Hee-Do Hong ◽  
Boo-Yong Lee

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinhuan Dou ◽  
Angela Cánovas ◽  
Luiz F. Brito ◽  
Ying Yu ◽  
Flavio S. Schenkel ◽  
...  

Understanding heat stress physiology and identifying reliable biomarkers are paramount for developing effective management and mitigation strategies. However, little is known about the molecular mechanisms underlying thermal tolerance in animals. In an experimental model of Sprague–Dawley rats subjected to temperatures of 22 ± 1°C (control group; CT) and 42°C for 30 min (H30), 60 min (H60), and 120 min (H120), RNA-sequencing (RNA-Seq) assays were performed for blood (CT and H120), liver (CT, H30, H60, and H120), and adrenal glands (CT, H30, H60, and H120). A total of 53, 1,310, and 1,501 differentially expressed genes (DEGs) were significantly identified in the blood (P < 0.05 and |fold change (FC)| >2), liver (P < 0.01, false discovery rate (FDR)–adjusted P = 0.05 and |FC| >2) and adrenal glands (P < 0.01, FDR-adjusted P = 0.05 and |FC| >2), respectively. Of these, four DEGs, namely Junb, P4ha1, Chordc1, and RT1-Bb, were shared among the three tissues in CT vs. H120 comparison. Functional enrichment analyses of the DEGs identified in the blood (CT vs. H120) revealed 12 biological processes (BPs) and 25 metabolic pathways significantly enriched (FDR = 0.05). In the liver, 133 BPs and three metabolic pathways were significantly detected by comparing CT vs. H30, H60, and H120. Furthermore, 237 BPs were significantly (FDR = 0.05) enriched in the adrenal glands, and no shared metabolic pathways were detected among the different heat-stressed groups of rats. Five and four expression patterns (P < 0.05) were uncovered by 73 and 91 shared DEGs in the liver and adrenal glands, respectively, over the different comparisons. Among these, 69 and 73 genes, respectively, were proposed as candidates for regulating heat stress response in rats. Finally, together with genome-wide association study (GWAS) results in cattle and phenome-wide association studies (PheWAS) analysis in humans, five genes (Slco1b2, Clu, Arntl, Fads1, and Npas2) were considered as being associated with heat stress response across mammal species. The datasets and findings of this study will contribute to a better understanding of heat stress response in mammals and to the development of effective approaches to mitigate heat stress response in livestock through breeding.


Author(s):  
Kuswati Kuswati ◽  
Djoko Prakosa ◽  
Brian Wasita ◽  
Nanang Wiyono

<p>BACKGROUND<br />Stress is one of the factors that cause apoptosis in neuronal cells. Centella<br />asiatica has a neuroprotective effect that can inhibit apoptosis. This study<br />aimed to examine the effect of Centella asiatica ethanol extract on B-cell<br />lymphoma 2 (Bcl-2) protein expression in the prefrontal cortex of rats.</p><p>METHODS<br />An experimental study was conducted on 34 brain tissue samples from male<br />Sprague Dawley rats exposed to chronic restraint stress for 21 days. The<br />samples were taken from following groups: non-stress group K, negative<br />control group P1 (stress + arabic gum powder), P2 (stress + C.asiatica at<br />150 mg/kgBW), P3 (stress + C.asiatica at 300 mg/kg BW), P4 (stress +<br />C.asiatica at 600 mg/kg body weight) and positive control group P5 (stress<br />+ fluoxetine at 10 mg/kgBW). The samples were made into sections that<br />were stained immunohistochemically using Bcl-2 antibody to determine the<br />percentage of cells expressing Bcl-2. Data were analyzed using one way<br />ANOVA test followed by a post - hoc test.</p><p>RESULTS<br />There were significant differences in mean Bcl-2 expression between the<br />groups receiving Centella asiatica compared with the non-stress group and<br />stress-only group (negative control group) (p&lt;0.05). The results were<br />comparable to those of the fluoxetine treatment group.</p><p>CONCLUSION</p><p>The Centella asiatica ethanol extract was able to increase Bcl-2 expression<br />in the prefrontal cortex of Sprague Dawley rats exposed to restraint stress.<br />This study suggests that Centella asiatica may be useful in the treatment of<br />cerebral stress.</p>


Author(s):  
Kuswati Nugroho ◽  
Ety Sari Handayani ◽  
Zainuri Sabta Nugraha

Background <br />Stress induces neuronal cell damage in the hippocampus and prefrontal cortex. Propolis has a neuroprotective effect that can inhibit apoptosis and decrease neuronal cell count. This study aimed to determine the effect of propolis on neuronal cell count in hippocampal area CA1 and prefrontal cortex in Sprague Dawley rats with induced stress.<br /><br />Methods<br />A study of laboratory experimental design was conducted involving 24 male Sprague-Dawley Rattus norvegicus. The animals were randomly divided into 4 groups, i.e. controls (K), and stress groups P1, P2 and P3. Controls did not receive treatment, stress group (P1) received stress treatment, groups P2 and P3 received stress and propolis at 100 and 200 mg/kgBW, respectively. Stress and propolis were given for 14 days, followed by termination. The number of neurons in the hippocampal area CA1 and prefrontal cortex were counted. One way ANOVA was used to analyze the data.<br /><br />Results <br />The neuronal count in the hippocampal area CA1 and prefrontal cortex in the stress group (P1) was lower than in groups K, P2 and P3. There were significant differences in the neuronal count of the hippocampal area CA1 between P1 and P3 and P1 and K (p=0.019) and also in the neuronal count of the prefrontal cortex between P1 and P2, P3 and K (p=0.002).<br /><br />Conclusions <br />This study strongly suggest that propolis inhibits the decrease in neuronal count in in the hippocampal area CA1 and prefrontal cortex of Sprague Dawley rats with induced stress. The present study suggests a potential neuroprotective effect of propolis in the prevention of neurodegenerative disorders.


2005 ◽  
Vol 288 (6) ◽  
pp. R1783-R1790 ◽  
Author(s):  
Douglas G. Whyte ◽  
Alan Kim Johnson

Blood flow is redistributed from the viscera to the periphery during periods of heat stress to maximize heat loss. The heat-induced redistribution of blood flow is strongly influenced by nonthermal inputs such as hydration status. At present, little is known about where thermal and nonthermal information is integrated to generate an appropriate effector response. Recently, the periventricular tissue that surrounds the anteroventral third ventricle (AV3V) has been implicated in the integration of thermal and osmotic information. The purpose of the present study was to determine the effects of electrolytic lesions of the AV3V on the cardiovascular response to a passive heat stress in unanesthetized, free-moving male Sprague-Dawley rats. Core temperature was elevated at a constant rate of ∼0.03°C/min in sham- and AV3V-lesion rats using an infrared heat lamp. Changes in mesenteric and hindquarter vascular resistance were determined using Doppler flow probes, and heat-induced salivation was estimated using the spit-print technique. The rise in mean arterial pressure (MAP), heart rate (HR), and mesenteric resistance in response to elevations in core temperature were all attenuated in AV3V-lesion rats; however, hindquarter resistance was unaffected. Heat-induced salivation was also diminished. In addition, AV3V-lesion rats were more affected by the novelty of the experimental environment, resulting in a higher basal core temperature, HR, and MAP. These results indicate that AV3V lesions disrupt the cardiovascular and salivatory response to a passive heat stress in rats and produce an exaggerated stress-induced fever triggered by a novel environment.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 353-354
Author(s):  
Jinhuan Dou ◽  
Flavio Schenkel ◽  
Ying Yu ◽  
Yachun Wang

Abstract Understanding animal physiology and identifying reliable biomarkers may help to establish effective management strategies for the prevention of heat stress (HS). However, little is known about the molecular mechanism of mammal tolerance to high temperatures. In a previous study with Sprague-Dawley rats, we performed RNA-seq assays on the liver of rats in control (CT; 22 ℃, n = 5) and heat stress (HS120; 42 ℃ for 120 min, n = 5) groups. A total of 3,909 differential expression genes (DEGs, Q &lt; 0.05) were observed. This study was conducted to further examine the epigenetic landscape in the liver of rats under HS and identify transcription factors (TFs), as well as their regulated genes. Three liver tissues were selected from the RNA-seq samples and performed an Assay for Transpose Accessible Chromatin (ATAC-seq). Peaks meeting criteria of P&lt; 0.05 and |Fold Change| &gt;1.5 were considered as differential peaks. All ATAC-seq libraries generated an expected distribution of the insert fragment lengths, with the majority of fragments being small, which characterize inter-nucleosomal open chromatin, and progressively fewer fragments of larger size, which are spanning nucleosomes. The accessibility of transcriptional start sites (TSS) was significantly enriched. After merging data, 2,356 differential peaks showed CT having more accessible TSS than H120 and only 230 differential peaks showed H120 group having more accessible TSS than CT. Thirty-six and 22 TF motifs were predicted by up- and down-regulated differential peaks in H120 vs. CT. Together with the previous DEG results, we proposed candidate TFs annotated to Cebpa, Foxa4, and Sp3 DEGs, which are involved in the regulation of oxidative stress. In summary, we showed that nuclear chromatin in the liver of heat stressed rats was less open than that of control rats. We suggest that the TFs (Cebpa, Foxa4, and Sp3) may be involved in the physiological regulation of HS.


Author(s):  
Zahra Zamanian ◽  
Saeed Yousefinejad ◽  
Mohammad Reza Reza Zare ◽  
Fazel Rajabi ◽  
Zahra Hashemi ◽  
...  

Background: Exposure to heat stress can result in lipid parameters alterations as well as immunological responses. This study was aimed to investigate these alterations and responses at different humidity and temperatures levels under controlled laboratory conditions in adult male Sprague–Dawley rats. Methods: A total 15 adult male Sprague–Dawley rats, weighing between 200 and 250 g, 10-11 weeks of age, were used in the evaluation. After one week, animals were randomly divided into three equal groups of 5 animals each. Reference group (group1) was housed in the cage under WBGT of 20(1) according to experimental design. Also, animals were subjected to mild (WBGT of 29 ( 1)) and hotter (WBGT of 33(1)) conditions (8 hr/day for one day) in the exposure chamber as group2 and group3, respectively. At the end of exposure to heat stress, blood samples were collected from the heart of rats and different parameters were determined. Results: Based on results, acute heat exposure significantly caused a decrease in serum IgG, IgM, IgA of rats in the case group compared to control group (P<0.05). Conversely, acute heat exposure resulted in a significant increase in the levels of IgE (P<0.05). There was no statistical difference for the lipid parameters after exposure to acute heat stress compared with the control group (P > 0.05). Conclusion: Acute heat stress may affect immune responses depending on the intensity of the exposure. Higher environmental temperatures (WBGT≥32°C) cause more severe changes in plasma immunoglobulins.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.


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