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- Nolte, I. M., et al.
(författare)
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Genetic loci associated with heart rate variability and their effects on cardiac disease risk
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74 < r(g) < -0.55) and blood pressure (-0.35 < r(g) < -0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants (GNG11, RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.
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- Giacobbo, B., et al.
(författare)
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Social stress-dependent changes on behavior and inflammatory parameters in animals with HPA-axis disruption
- 2020
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 47:Suppl.1, s. S639-S640
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim/Introduction: Chronic stress is associated with aderegulation of the hypothalamus-pituitary adrenal (HPA)axis and can result in behavioral abnormalities, such asdepressive behavior. Adrenalectomy (ADX) inhibits theproduction and release of corticosterone, impairingthe response towards stressors, and thus may preventstress-induced depressive behavior. We aim to determinebehavioral and neuroinflammatory effects of HPA-axisdisruption via bilateral adrenalectomy (ADX) in animalssubmitted to repeated social defeat (RSD).Materials and Methods: 8-weeks old male Wistar rats were dividedinto four groups: ADX+RSD; ADX+Control; Sham+RSD;Sham+Control. Seven days after ADX surgery, animals weresubmitted to a 5 days RSD or Control protocols. One- andtwo days after the last RSD trial, animals went through anopen field and social interaction test, respectively. 14 daysafter RSD, animals went through a 30 minutes [11C]-PBR28scan for microglia activation. Multifactorial ANOVA wasperformed for statistical assessment.Results: There was asignificant effect of RSD (p=0.038) and ADX (p=0.049) onthe social interaction of the animals, as well as an interactionbetween surgery and RSD (p=0.042). Post-hoc analysisshowed a significantly lower social interaction of Sham+RSDwhen compared with the other groups (vs. Control+ADX,p=0.032; Control+Sham, p=0.023; ADX+RSD, p=0.035).Open field analysis showed no anxiety-like behavior norlocomotion effect of RSD or ADX (p>0.05). Microglialactivation assessed through [11C]-PBR28 also showed noeffect of RSD or ADX (p>0.05).Conclusion: HPA-axis signalingdisruption is able to counterbalance the impairment on thesocial behavior of these animals. In contrast, no effects ofADX or RSD were observed in other behavioral paradigms.Neuroinflammation was also not observed two weeks afterthe RSD, suggesting that the inflammatory response ofmicroglial cells is too mild to be detected by PET or thatneuroinflammation was only transient and already resolvedat the time of measurement.References: None
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