Serotonin transporter null male mouse pups have lower ventilation in air and 5% CO2 at postnatal ages P15 and P25

Penatti, Eliana M.; Barina, Alexis; Schram, Koren; Li, Aihua; Nattie, Eugene E.

doi:10.1016/j.resp.2011.02.006

Cited by 15 publications

(6 citation statements)

References 9 publications

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“…Consistent with this conclusion is the observation that in serotonin-deficient mice, gasping is markedly attenuated during a short time window in postnatal development [44]. Additionally, recent studies in mice with genetic impairment to serotonergic neuromodulation have demonstrated that males are vulnerable to a loss of chemosensitive responsiveness [45] [46]. However, while both the failure to effectively gasp/autoresuscitate [11] and disturbances in serotonergic mechanisms [47] appear critical in the disease mechanisms of SIDS, other biological factors may also be involved with the etiology of SIDS.…”

Section: Discussionmentioning

confidence: 68%

Post-Hypoxic Recovery of Respiratory Rhythm Generation Is Gender Dependent

Garcia¹,

Rotem-Kohavi²,

Doi

et al. 2013

PLoS ONE

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The preBötzinger complex (preBötC) is a critical neuronal network for the generation of breathing. Lesioning the preBötC abolishes respiration, while when isolated in vitro, the preBötC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBötC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBötC. Recordings of respiratory activity from neonatal mice (P10–13) show that sustained post-hypoxic depression occurs with greater frequency in males compared to females. Moreover, extracellular population recordings from the preBötC in neonatal brainstem slices (P10–13) reveal that the time to the first inspiratory burst following reoxygenation (TTFB) is significantly delayed in male rhythmogenesis when compared to the female rhythms. Altering activity of ATP sensitive potassium channels (KATP) with either the agonist, diazoxide, or the antagonist, tolbutamide, eliminates differences in TTFB. By contrast, glucose supplementation improves post-hypoxic recovery of female but not male rhythmogenesis. We conclude that post-hypoxic recovery of respiration is gender dependent, which is, in part, centrally manifested at the level of the preBötC. Moreover, these findings provide potential insight into the basis of increased male vulnerability in a variety of conditions such as Sudden Infant Death Syndrome (SIDS).

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Section: Discussionmentioning

confidence: 68%

Post-Hypoxic Recovery of Respiratory Rhythm Generation Is Gender Dependent

Garcia¹,

Rotem-Kohavi²,

Doi

et al. 2013

PLoS ONE

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“…Thus, in the absence of endogenous serotonin activation, gasping at the network level is abolished (Tryba et al, 2006). This finding has been confirmed in intact animals using several approaches aimed at depleting serotonergic neuromodulation within the brainstem (Li and Nattie, 2008; Cummings et al, 2009, 2011; Penatti et al, 2011). Specifically perinatal loss of brainstem serotonin neurons compromises the ability of rats to survive (Cummings et al, 2009, 2011).…”

Section: Sids and Central Cardio-respiratory Controlmentioning

confidence: 63%

“…In mice with disrupted serotonergic reuptake, hypercapnic chemosensitivity is disrupted as early as postnatal day (P) 15 (Penatti et al, 2011). Interestingly, this loss of chemosensitivity is biased toward the male gender (Li and Nattie, 2008; Penatti et al, 2011). Therefore, changes in the serotonergic network can potentially increase susceptibility to SIDS in both an age and gender dependent manner.…”

Section: The Influence Of Gender and Age Over Cardio-respiratory Fmentioning

confidence: 99%

The physiological determinants of Sudden Infant Death Syndrome

Garcia¹,

Koschnitzky²,

Ramirez

2013

Respiratory Physiology & Neurobiology

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It is well-established that environmental and biological risk factors contribute to Sudden Infant Death Syndrome (SIDS). There is also growing consensus that SIDS requires the intersection of multiple risk factors that result in the failure of an infant to overcome cardio-respiratory challenges. Thus, the critical next steps in understanding SIDS are to unravel the physiological determinants that actually cause the sudden death, to synthesize how these determinants are affected by the known risk factors, and to develop novel ideas for SIDS prevention. In this review, we will examine current and emerging perspectives related to cardio-respiratory dysfunctions in SIDS. Specifically, we will review: (1) the role of the preBötzinger complex (preBötC) as a multi-functional network that is critically involved in the failure to adequately respond to hypoxic and hypercapnic challenges; (2) the potential involvement of the pre-BötC in the gender and age distributions that are characteristic for SIDS; (3) the link between SIDS and prematurity; and (4) the potential relationship between SIDS, auditory function, and central chemosensitivity. Each section underscores the importance of marrying the epidemiological and pathological data to experimental data in order to understand the physiological determinants of this syndrome. We hope that a better understanding will lead to novel ways to reduce the risk to succumb to SIDS.

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“…The oxygen concentration in the chamber was measured using an electrochemical analyzer (Maxtec OM-25RME). The flows of oxygen and nitrogen were carefully regulated using flow meters (Cole-Palmer) to maintain a fresh O 2 gas flow rate 8 -10 times the calculated oxygen consumption of the litter and mother (59). Both mothers and pups tolerated this exposure well, as also reported by others (8,24).…”

Section: Methodsmentioning

confidence: 85%

Soluble guanylate cyclase modulates alveolarization in the newborn lung

Bachiller

Cornog²,

Kato

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Nitric oxide (NO) regulates lung development through incompletely understood mechanisms. NO controls pulmonary vascular smooth muscle cell (SMC) differentiation largely through stimulating soluble guanylate cyclase (sGC) to produce cGMP and increase cGMP-mediated signaling. To examine the role of sGC in regulating pulmonary development, we tested whether decreased sGC activity reduces alveolarization in the normal and injured newborn lung. For these studies, mouse pups with gene-targeted sGC-α1 subunit truncation were used because we determined that they have decreased pulmonary sGC enzyme activity. sGC-α1 knockout (KO) mouse pups were observed to have decreased numbers of small airway structures and lung volume compared with wild-type (WT) mice although lung septation and body weights were not different. However, following mild lung injury caused by breathing 70% O2, the sGC-α1 KO mouse pups had pronounced inhibition of alveolarization, as evidenced by an increase in airway mean linear intercept, reduction in terminal airway units, and decrease in lung septation and alveolar openings, as well as reduced somatic growth. Because cGMP regulates SMC phenotype, we also tested whether decreased sGC activity reduces lung myofibroblast differentiation. Cellular markers revealed that vascular SMC differentiation decreased, whereas myofibroblast activation increased in the hyperoxic sGC-α1 KO pup lung. These results indicate that lung development, particularly during hyperoxic injury, is impaired in mouse pups with diminished sGC activity. These studies support the investigation of sGC-targeting agents as therapies directed at improving development in the newborn lung exposed to injury.

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Serotonin transporter null male mouse pups have lower ventilation in air and 5% CO2 at postnatal ages P15 and P25

Cited by 15 publications

References 9 publications

Post-Hypoxic Recovery of Respiratory Rhythm Generation Is Gender Dependent

Post-Hypoxic Recovery of Respiratory Rhythm Generation Is Gender Dependent

The physiological determinants of Sudden Infant Death Syndrome

Soluble guanylate cyclase modulates alveolarization in the newborn lung

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