scholarly journals Effect of serotonin transporter genotype on carbon dioxide-induced fear-related behavior in mice

2020 ◽  
Vol 34 (12) ◽  
pp. 1408-1417
Author(s):  
Nicole K Leibold ◽  
Daniel LA van den Hove ◽  
Magdalena T Weidner ◽  
Gordon F Buchanan ◽  
Harry WM Steinbusch ◽  
...  

Background: Inhaling 35% carbon dioxide induces an emotional and symptomatic state in humans closely resembling naturally occurring panic attacks, the core symptom of panic disorder. Previous research has suggested a role of the serotonin system in the individual sensitivity to carbon dioxide. In line with this, we previously showed that a variant in the SLC6A4 gene, encoding the serotonin transporter, moderates the fear response to carbon dioxide in humans. To study the etiological basis of carbon dioxide-reactivity and panic attacks in more detail, we recently established a translational mouse model. Aim: The purpose of this study was to investigate whether decreased expression of the serotonin transporter affects the sensitivity to carbon dioxide. Methods: Based on our previous work, wildtype and serotonin transporter deficient (+/–, –/–) mice were monitored while being exposed to carbon dioxide-enriched air. In wildtype and serotonin transporter +/– mice, also cardio-respiration was assessed. Results: For most behavioral measures under air exposure, wildtype and serotonin transporter +/– mice did not differ, while serotonin transporter –/– mice showed more fear-related behavior. Carbon dioxide exposure evoked a marked increase in fear-related behaviors, independent of genotype, with the exception of time serotonin transporter –/– mice spent in the center zone of the modified open field test and freezing in the two-chamber test. On the physiological level, when inhaling carbon dioxide, the respiratory system was strongly activated and heart rate decreased independent of genotype. Conclusion: Carbon dioxide is a robust fear-inducing stimulus. It evokes inhibitory behavioral responses such as decreased exploration and is associated with a clear respiratory profile independent of serotonin transporter genotype.

2019 ◽  
Vol 32 (1) ◽  
pp. 1-10
Author(s):  
Alexander Baxter ◽  
Elizabeth K. Wood ◽  
Christina S. Barr ◽  
Daniel B. Kay ◽  
Stephen J. Suomi ◽  
...  

AbstractEnvironmental and biological factors contribute to sleep development during infancy. Parenting plays a particularly important role in modulating infant sleep, potentially via the serotonin system, which is itself involved in regulating infant sleep. We hypothesized that maternal neglect and serotonin system dysregulation would be associated with daytime sleep in infant rhesus monkeys. Subjects were nursery-reared infant rhesus macaques (n = 287). During the first month of life, daytime sleep-wake states were rated bihourly (0800–2100). Infants were considered neglected (n = 16) if before nursery-rearing, their mother repeatedly failed to retrieve them. Serotonin transporter genotype and concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) were used as markers of central serotonin system functioning. t tests showed that neglected infants were observed sleeping less frequently, weighed less, and had higher 5-HIAA than non-neglected nursery-reared infants. Regression revealed that serotonin transporter genotype moderated the relationship between 5-HIAA and daytime sleep: in subjects possessing the Ls genotype, there was a positive correlation between 5-HIAA and daytime sleep, whereas in subjects possessing the LL genotype there was no association. These results highlight the pivotal roles that parents and the serotonin system play in sleep development. Daytime sleep alterations observed in neglected infants may partially derive from serotonin system dysregulation.


2021 ◽  
Vol 9 (4) ◽  
pp. 797
Author(s):  
Davide Mugetti ◽  
Mattia Tomasoni ◽  
Paolo Pastorino ◽  
Giuseppe Esposito ◽  
Vasco Menconi ◽  
...  

The Mycobacterium fortuitum group (MFG) consists of about 15 species of fast-growing nontuberculous mycobacteria (NTM). These globally distributed microorganisms can cause diseases in humans and animals, especially fish. The increase in the number of species belonging to MFG and the diagnostic techniques panel do not allow to clarify their real clinical significance. In this study, biomolecular techniques were adopted for species determination of 130 isolates derived from fish initially identified through biochemical tests as NTM belonging to MFG. Specifically, gene sequencing and phylogenetic analysis were used based on a fragment of the gene encoding the 65 KDa heat shock protein (hsp65). The analyzes made it possible to confirm that all the isolates belong to MFG, allowing to identify the strains at species level. Phylogenetic analysis substantially confirmed what was obtained by gene sequencing, except for six strains; this is probably due to the sequences present in NCBI database. Although the methodology used cannot represent a univocal identification system, this study has allowed us to evaluate its effectiveness as regards the species of MFG. Future studies will be necessary to apply these methods with other gene fragments and to clarify the real pathogenic significance of the individual species of this group of microorganisms.


Author(s):  
Sabrina I. Hanswijk ◽  
Daan van Rooij ◽  
Jaap Oosterlaan ◽  
Marjolein Luman ◽  
Pieter J. Hoekstra ◽  
...  

A differential method for comparing the compressibilities of gases at pressures below 1 atm. has been developed in which many of the errors inherent in methods employed previously have been to a large extent eliminated, especially those due to meniscus volume changes and capillary depression. Using pure nitrogen as a standard the low-pressure isothermals of carbon monoxide, carbon dioxide, nitrous oxide, oxygen, ethylene and propane have been determined at a temperature of 22-05° C. The deviations of the individual points from straight lines do not in most cases exceed 2 parts in 100,000. In no case, even with propane, was any curvature in the isotherms detectable. The contention of Moles and other recent workers that the molecular weights of liquefiable gases can be determined to a high degree of accuracy by linear extrapolation is rendered highly probable by this fresh evidence.


2015 ◽  
Vol 309 (10) ◽  
pp. L1164-L1173 ◽  
Author(s):  
Michiel Alexander de Raaf ◽  
Yvet Kroeze ◽  
Anthonieke Middelman ◽  
Frances S. de Man ◽  
Helma de Jong ◽  
...  

Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.


2003 ◽  
Vol 99 (4) ◽  
pp. 834-840 ◽  
Author(s):  
Walter Klimscha ◽  
Roman Ullrich ◽  
Christian Nasel ◽  
Wolfgang Dietrich ◽  
Udo M. Illievich ◽  
...  

Background Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv). Methods Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 microg x kg-1 x min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics. Results Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 microg x kg-1 x min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 +/- 0.27 and 0.49 +/- 0.28 ml. 100 g-1 x min-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.9 +/- 0.8 and 1.6 +/- 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 +/- 0.95 and 1.54 +/- 0.83 cm x s-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.86 +/- 0.59 and 1.79 +/- 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ. Conclusion High-dose remifentanil decreases rCBF and mean CBFv without impairing cerebrovascular carbon dioxide reactivity. This, together with its known short duration of action, makes remifentanil a useful agent in the intensive care unit when sedation that can be titrated rapidly is required.


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