scholarly journals Multi-Transcript Level Profiling Revealed Distinct mRNA, miRNA, and tRNA-Derived Fragment Bio-Signatures for Coping Behavior Linked Haplotypes in HPA Axis and Limbic System

2021 ◽  
Vol 12 ◽  
Author(s):  
Kevin Gley ◽  
Frieder Hadlich ◽  
Nares Trakooljul ◽  
Fiete Haack ◽  
Eduard Murani ◽  
...  

The molecular basis of porcine coping behavior (CB) relies on a sophisticated interplay of genetic and epigenetic features. Deep sequencing technologies allowed the identification of a plethora of new regulatory small non-coding RNA (sncRNA). We characterized mRNA and sncRNA profiles of central parts of the physiological stress response system including amygdala, hippocampus, hypothalamus and adrenal gland using systems biology for integration. Therefore, ten each of high- (HR) and low- (LR) reactive pigs (n = 20) carrying a CB associated haplotype in a prominent QTL-region on SSC12 were selected for mRNA and sncRNA expression profiling. The molecular markers related to the LR group included ATP1B2, MPDU1, miR-19b-5p, let-7g-5p, and 5′-tiRNALeu in the adrenal gland, miR-194a-5p, miR-125a-5p, miR-7-1-5p, and miR-107-5p in the hippocampus and CBL and PVRL1 in the hypothalamus. Interestingly, amygdalae of the LR group showed 5′-tiRNA and 5′-tRF (5′-tRFLys, 5′-tiRNALys, 5′-tiRNACys, and 5′-tiRNAGln) enrichment. Contrarily, molecular markers associated with the HR group encompassed miR-26b-5p, tRNAArg, tRNAGlyiF in the adrenal gland, IGF1 and APOD in the amygdala and PBX1, TOB1, and C18orf1 in the hippocampus and miR-24 in the hypothalamus. In addition, hypothalami of the HR group were characterized by 3′-tiRNA enrichment (3′-tiRNAGln, 3′-tiRNAAsn, 3′-tiRNAVal, 3′-tRFPro, 3′-tiRNACys, and 3′-tiRNAAla) and 3′-tRFs enrichment (3′-tRFAsn, 3′-tRFGlu, and 3′-tRFVal). These evidence suggest that tRNA-derived fragments and their cleavage activity are a specific marker for coping behavior. Data integration revealed new bio-signatures of important molecular interactions on a multi-transcript level in HPA axis and limbic system of pigs carrying a CB-associated haplotype.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kevin Gley ◽  
Eduard Murani ◽  
Nares Trakooljul ◽  
Manuela Zebunke ◽  
Birger Puppe ◽  
...  

Abstract The hypothalamic-pituitary-adrenal (HPA) axis is an important component of neuroendocrine stress regulation and coping behavior. Transcriptome profiles of the hypothalamus and adrenal gland were assessed to identify molecular pathways and candidate genes for coping behavior in pigs. Ten each of high- (HR) and low- (LR) reactive pigs (n = 20) were selected for expression profiling based haplotype information of a prominent QTL-region on SSC12 discovered in our previous genome-wide association study (GWAS) on coping behavior. Comparing the HR and LR pigs showed 692 differentially expressed genes (DEGs) in the adrenal gland and 853 DEGs in the hypothalamus, respectively. Interestingly, 47% (17 out of 36) of DEGs found in both tissues were located in GWAS regions identified on SSC12, indicating that there are significant functional positional candidate genes for coping behaviour. Pathway analysis assigned DEGs to glucocorticoid receptor signaling in the adrenal gland. Furthermore, oxidative phosphorylation, mitochondrial dysfunction, and NGF signaling as well as cholecystokinin/Gastrin-mediated were identified in the hypothalamus. We narrowed the list of candidate genes in GWAS regions by analyzing their DEGs in the HPA axis. The top identified transcripts, including ATP1B2, AURKB, MPDU1 and NDEL1 provide evidence for molecular correlates of coping behavior in GWAS regions.


2019 ◽  
Vol 73 ◽  
pp. 217-224
Author(s):  
Magdalena Kusek ◽  
Izabela Ciurej ◽  
Krzysztof Tokarski

This paper summarizes a series of studies aimed at characterizing the effects of stress-related changes in synaptic inputs to the hypothalamic paraventricular nucleus (PVN). This structure generates an integrated physiological stress response by activating the hypothalamus-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine neurons of the PVN play a key role in this process. They receive extensive excitatory and inhibitory innervation conveying information about interoceptive and exteroceptive stressful stimuli from a variety of sources within the brain. These synaptic inputs modulate the activity of PVN neurons, which regulates the amount of CRH released into the portal circulation of the anterior pituitary. It has been demonstrated that with either single or repeated stress sessions, the efficacy of excitatory and inhibitory synapses on parvocellular neuroendocrine neurons changes considerably, which may be related to repeated stress-induced sensitization of the HPA axis. The nature of these changes depends on the type of stress and its duration. Changes in synaptic inputs and the excitability of parvocellular neuroendocrine neurons are thought to be responsible for dysfunctions of the HPA axis observed in affective disorders. Assessing how this controlling function of PVN neurons is modulated in response to stress is crucial to our understanding of the pathophysiology of affective disorders.


2020 ◽  
Vol 32 (5) ◽  
pp. 1888-1898
Author(s):  
Melissa J. Hagan ◽  
Danielle S. Roubinov ◽  
W. Thomas Boyce ◽  
Nicole R. Bush

AbstractThere is emerging evidence that the development of problematic aggression in childhood may be associated with specific physiological stress response patterns, with both biological overactivation and underactivation implicated. This study tested associations between sex-specific patterns of stress responses across the sympathetic nervous system (SNS) and hypothalamic–pituitary–adrenal (HPA) axis and peer nominations of aggression among 271 kindergarten children (Mean age = 5.32 years; 52% Female; 44% White). Upon entry to kindergarten, children participated in a multidomain standardized stress paradigm. Changes in pre-ejection period (PEP) and salivary cortisol were assessed. On a separate day, children provided peer ratings of physical and relational aggression in a standardized interview. As expected, there was a significant three-way interaction between PEP, cortisol reactivity, and sex, but only for physical aggression. Among boys, cortisol reactivity was positively associated with physical aggression only for those with higher SNS reactivity. Findings suggest that for boys, asymmetrical and symmetrical HPA/SNS reactivity may be associated with lower and higher risk for peer-directed physical aggression, respectively. Understanding the complex associations between multisystem physiology, child sex and peer-directed aggression in early childhood may offer insight into individual differences underlying the emergence of behavioral dysregulation in early peer contexts.


2021 ◽  
Vol 239 ◽  
pp. 105940
Author(s):  
Laura Simões Andrade ◽  
Domingos Garrone-Neto ◽  
Manuela Alves Nobre Sales ◽  
Luciana Rodrigues de Souza-Bastos ◽  
Ursulla Pereira Souza ◽  
...  

2009 ◽  
Vol 73 (4) ◽  
pp. 609-614 ◽  
Author(s):  
Remington J. Moll ◽  
Joshua J. Millspaugh ◽  
Jeff Beringer ◽  
Joel Sartwell ◽  
Rami J. Woods ◽  
...  

2014 ◽  
Vol 54 (2) ◽  
pp. 187 ◽  
Author(s):  
I. Zulkifli ◽  
Y. M. Goh ◽  
B. Norbaiyah ◽  
A. Q. Sazili ◽  
M. Lotfi ◽  
...  

The present study aimed to provide a comparative analysis of the effects of penetrative stunning, non-penetrative stunning and post-slaughter stunning on biochemical parameters and electroencephalogram (EEG) associated with stress in heifers and steers. Ten animals were assigned to each of the following four treatment groups: (1) animals were subjected to conventional halal slaughter (a clean incision through the structures on the ventral neck at the approximate level of vertebrae C2–C3 – the trachea, oesophagus, carotid arteries and jugular veins) and post-cut penetrating mechanical stun within 10–20 s of the halal cut (U); (2) high-power non-penetrating mechanical stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (HPNP); (3) low-power non-penetrating mechanical percussive stunning using a mushroom-headed humane killer, followed by conventional halal slaughter (LPNP); and (4) penetrative stunning using a captive-bolt pistol humane killer, followed by conventional halal slaughter (P). For each animal, blood samples and electroencephalogram recordings were taken before stunning, post-stunning (if applicable) and post-slaughter, and plasma concentrations of cortisol, adrenocorticotrophic hormone (ACTH), adrenaline, noradrenaline and β-endorphin were determined. Irrespective of the stunning method, except for percentage change in plasma concentrations of noradrenaline, the values of blood parameters attained before and after stunning were not significantly different. The plasma noradrenaline concentration of the HPNP animals was significantly elevated following stunning. Following slaughter, the percentage change of plasma ACTH concentration in the P animals was significantly elevated. Neither stunning method nor sampling time had a significant effect on plasma β-endorphin concentration. On the basis of the EEG results, penetrative stunning seemed to be better in maximising the possibility of post-stunning insensibility, whereas U animals appeared to demonstrate an evident increase in EEG activity which is consistent with the presence of post-slaughter noxious stimuli associated with tissue cut and injury. The U animals had consistently higher, if not the highest, RMS values than did other stunned animals. This indicates a degree of EEG changes associated with stress and pain. On the basis of EEG data, our results suggested that penetrative stunning would be the most reliable method of ensuring insensibility and minimising pain. However, at slaughter, the P animals showed a dramatic elevation in the percentage change of circulating ACTH, suggesting physiological stress response. On a cautionary note, the results are not unequivocal, and it may be that the range of analyses available to researchers at this point of time are not sufficiently specific to allow definitive conclusions to be drawn.


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