scholarly journals Intermittent severe hypoxia induces plasticity within serotonergic and catecholaminergic neurons in the neonatal rat ventrolateral medulla

2016 ◽  
Vol 120 (11) ◽  
pp. 1277-1287 ◽  
Author(s):  
Scott A. Givan ◽  
Kevin J. Cummings
Keyword(s):  
Tyrosine Hydroxylase ◽  
Tryptophan Hydroxylase ◽  
Neonatal Rat ◽  
Severe Hypoxia ◽  
Autonomic Response ◽  
Ventrolateral Medulla ◽  
Dopa Decarboxylase ◽  
Catecholaminergic Neurons ◽  
Catecholaminergic System ◽  
Rat Pups

5-HT neurons contribute to autoresuscitation and survival during intermittent severe hypoxia (IsH). In adults, catecholaminergic neurons in the ventrolateral medulla (VLM) contribute to the autonomic response to hypoxia. We hypothesized that 1) catecholaminergic neurons in the neonatal VLM are activated following IsH, 2) this activation is compromised following an acute loss of brain stem 5-HT, and 3) IsH induces cellular and/or transcriptomic plasticity within catecholaminergic and serotonergic neurons that are within or project to the VLM, respectively. To test these hypotheses, we treated rat pups with 6-fluorotryptophan, a tryptophan hydroxylase (TPH) inhibitor, and then exposed treated and vehicle controls to IsH or air. Along with immunohistochemistry to detect tyrosine hydroxylase (TH)- or Fos-positive neurons, we used RNA sequencing to resolve the effects of IsH and 5-HT deficiency on the expression of serotonergic and catecholaminergic system genes in the VLM. 5-HT deficiency compromised autoresuscitation and survival. IsH significantly increased the number of identifiable TH-positive VLM neurons, an effect enhanced by 5-HT deficiency ( P = 0.003). Contrary to our hypothesis, 5-HT-deficient pups had significantly more Fos-positive neurons following IsH ( P = 0.008) and more activated TH-positive neurons following IsH or air ( P = 0.04). In both groups the expression of the 5-HT transporter and TPH2 was increased following IsH. In 5-HT-deficient pups, the expression of the inhibitory 5-HT1A receptor was decreased following IsH, while the expression of DOPA decarboxylase was increased. These data show that the serotonergic and catecholaminergic systems in the VLM of the neonatal rat are dynamically upregulated by IsH, potentially adapting cardiorespiratory responses to severe hypoxia.

Infrasonic Stimulation Induced Fos Expression in Medullary Catecholaminergic Neurons in Rats

1998 ◽  
Vol 17 (3) ◽  
pp. 133-139 ◽  
Author(s):  
Xiao-Hui Xing ◽  
Ling Wang ◽  
Zhi-Ren Rao ◽  
Jing-Zao Chen
Keyword(s):  
Tyrosine Hydroxylase ◽  
Reticular Formation ◽  
Nucleus Tractus Solitarii ◽  
Immunohistochemical Method ◽  
Ventrolateral Medulla ◽  
Catecholaminergic Neurons ◽  
Fos Expression

To clarify the effects of infrasound on the medulla, catecholaminergic neurons in the medulla expressing Fos were investigated in the rats by immunohistochemical method. After exposure to infrasound (8Hz, 120dB) for 2 hours, animals were sacrificed and sections of the medulla were stained immunohistochemically for Fos and tyrosine hydroxylase (TH). Many Fos-like immunoreactive neurons were found in the nucleus tractus solitarii (NTS) and Ventrolateral medulla (VLM) at the middle and caudal levels of medulla, only a few of them scattered in the reticular formation between NTS and VLM. Some Fos immunoreactive neurons were also labeled with TH. These results indicated that medulla was sensitive to infrasonic stimulation and some medullary catecholaminergic neurons might be involved in the responses to the stress produced by infrasound.

scholarly journals Eliminating medullary 5-HT neurons delays arousal and decreases the respiratory response to repeated episodes of hypoxia in neonatal rat pups

2016 ◽  
Vol 120 (5) ◽  
pp. 514-525 ◽  
Author(s):  
Robert A. Darnall ◽  
Robert W. Schneider ◽  
Christine M. Tobia ◽  
Kathryn G. Commons
Keyword(s):  
Respiratory Rate ◽  
Tryptophan Hydroxylase ◽  
Defense Mechanism ◽  
Sudden Infant Death ◽  
Neonatal Rat ◽  
Sudden Infant ◽  
Hypoxia Exposure ◽  
Rat Pups ◽  
Medullary Raphe ◽  
Arousal Response

Arousal from sleep is a critical defense mechanism when infants are exposed to hypoxia, and an arousal deficit has been postulated as contributing to the etiology of the sudden infant death syndrome (SIDS). The brainstems of SIDS infants are deficient in serotonin (5-HT) and tryptophan hydroxylase (TPH) and have decreased binding to 5-HT receptors. This study explores a possible connection between medullary 5-HT neuronal activity and arousal from sleep in response to hypoxia. Medullary raphe 5-HT neurons were eliminated from neonatal rat pups with intracisterna magna (CM) injections of 5,7-dihydroxytryptamine (DHT) at P2-P3. Each pup was then exposed to four episodes of hypoxia during sleep at three developmental ages (P5, P15, and P25) to produce an arousal response. Arousal, heart rate, and respiratory rate responses of DHT-injected pups were compared with pups that received CM artificial cerebrospinal fluid (aCSF) and those that received DHT but did not have a significant reduction in medullary 5-HT neurons. During each hypoxia exposure, the time to arousal from the onset of hypoxia (latency) was measured together with continuous measurements of heart and respiratory rates, oxyhemoglobin saturation, and chamber oxygen concentration. DHT-injected pups with significant losses of medullary 5-HT neurons exhibited significantly longer arousal latencies and decreased respiratory rate responses to hypoxia compared with controls. These results support the hypothesis that in newborn and young rat pups, 5-HT neurons located in the medullary raphe contribute to the arousal response to hypoxia. Thus alterations medullary 5-HT mechanisms might contribute to an arousal deficit and contribute to death in SIDS infants.

Differential immunodetection of l ‐DOPA decarboxylase and tyrosine hydroxylase in the vertebrate retina

2009 ◽  
Vol 27 (5) ◽  
pp. 469-476 ◽  
Author(s):  
Rosilane Taveira da Silva ◽  
Jan Nora Hokoç ◽  
Fernando Garcia Mello ◽  
Patrícia Franca Gardino
Keyword(s):  
Tyrosine Hydroxylase ◽  
Dopa Decarboxylase ◽  
Vertebrate Retina

Behavioral Components of Milk-Induced Activation in Neonatal Rat Pups

1996 ◽  
Vol 82 (3) ◽  
pp. 903-911 ◽  
Author(s):  
Steven M. Specht ◽  
Richard G. Burright ◽  
Linda Patia Spear
Keyword(s):  
Brain Stimulation ◽  
Principal Components ◽  
Behavioral Activation ◽  
Neural Substrates ◽  
Neonatal Rat ◽  
Exact Nature ◽  
Electrical Brain Stimulation ◽  
Global Pattern ◽  
Rat Pups ◽  
Components Analysis

Neonatal rat pups exhibit a complex constellation of behaviors in response to a variety of salient stimuli such as the odor of milk or maternal saliva, stroking with a soft brush, electrical brain stimulation, and intraoral infusions of milk. Although psychobiologists have used the term “behavioral activation” to refer to such behavioral displays, the exact nature of “behavioral activation” and its underlying neural substrates have yet to be elucidated. This study was undertaken to characterize “behavioral activation” quantitatively to describe and define this apparently global pattern of response in terms of possible underlying components. Principal components analysis suggested that “behavioral activation” may be comprised of separable ingestive, exploratory, and locomotor behavioral “assemblies.”

Long-term modulation of tyrosine hydroxylase activity and expression by endothelin-1 and -3 in the rat anterior and posterior hypothalamus

2008 ◽  
Vol 294 (3) ◽  
pp. R905-R914 ◽  
Author(s):  
Guadalupe Perfume ◽  
Sabrina L. Nabhen ◽  
Karla Riquelme Barrera ◽  
María G. Otero ◽  
Liliana G. Bianciotti ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Cardiovascular Effects ◽  
Receptor Activation ◽  
Catecholaminergic Neurons ◽  
Endothelin System ◽  
Catecholaminergic Transmission ◽  
Underlying Mechanisms ◽  
G Protein Coupled ◽  
The Brain

Brain catecholamines are involved in the regulation of biological functions, including cardiovascular activity. The hypothalamus presents areas with high density of catecholaminergic neurons and the endothelin system. Two hypothalamic regions intimately related with the cardiovascular control are distinguished: the anterior (AHR) and posterior (PHR) hypothalamus, considered to be sympathoinhibitory and sympathoexcitatory regions, respectively. We previously reported that endothelins (ETs) are involved in the short-term tyrosine hydroxylase (TH) regulation in both the AHR and PHR. TH is crucial for catecholaminergic transmission and is tightly regulated by well-characterized mechanisms. In the present study, we sought to establish the effects and underlying mechanisms of ET-1 and ET-3 on TH long-term modulation. Results showed that in the AHR, ETs decreased TH activity through ETB receptor activation coupled to the nitric oxide, phosphoinositide, and CaMK-II pathways. They also reduced total TH level and TH phosphorylated forms (Ser 19 and 40). Conversely, in the PHR, ETs increased TH activity through a G protein-coupled receptor, likely an atypical ET receptor or the ETC receptor, which stimulated the phosphoinositide and adenylyl cyclase pathways, as well as CaMK-II. ETs also increased total TH level and the Ser 19, 31, and 40 phosphorylated sites of the enzyme. These findings support that ETs are involved in the long-term regulation of TH activity, leading to reduced sympathoinhibition in the AHR and increased sympathoexcitation in the PHR. Present and previous studies may partially explain the cardiovascular effects produced by ETs when applied to the brain.

scholarly journals Loss of Trefoil Factor 2 Sensitizes Rat Pups to Systemic Infection with the Neonatal PathogenEscherichia coliK1

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Alex J. McCarthy ◽  
George M. H. Birchenough ◽  
Peter W. Taylor
Keyword(s):  
Small Intestine ◽  
Neonatal Rat ◽  
Mucus Layer ◽  
Trefoil Factor ◽  
Wild Type ◽  
Content Type ◽  
Distal Small Intestine ◽  
E Coli ◽  
Rat Pups ◽  
Trefoil Factor 2

ABSTRACTGastrointestinal (GI) colonization of 2-day-old (P2) rat pups withEscherichia coliK1 results in translocation of the colonizing bacteria across the small intestine, bacteremia, and invasion of the meninges, with animals frequently succumbing to lethal infection. Infection, but not colonization, is strongly age dependent; pups become progressively less susceptible to infection over the P2-to-P9 period. Colonization leads to strong downregulation of the gene encoding trefoil factor 2 (Tff2), preventing maturation of the protective mucus barrier in the small intestine. Trefoil factors promote mucosal homeostasis. We investigated the contribution of Tff2 to protection of the neonatal rat fromE. coliK1 bacteremia and tissue invasion. Deletion oftff2, using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, sensitized P9 pups toE. coliK1 bacteremia. There were no differences betweentff2−/−homozygotes and the wild type with regard to the dynamics of GI colonization. Loss of the capacity to elaborate Tff2 did not impact GI tract integrity or the thickness of the small-intestinal mucus layer but, in contrast to P9 wild-type pups, enabledE. coliK1 bacteria to gain access to epithelial surfaces in the distal region of the small intestine and exploit an intracellular route across the epithelial monolayer to enter the blood circulation via the mesenteric lymphatic system. Although primarily associated with the mammalian gastric mucosa, we conclude that loss of Tff2 in the developing neonatal small intestine enables the opportunistic neonatal pathogenE. coliK1 to enter the compromised mucus layer in the distal small intestine prior to systemic invasion and infection.

Influence of adenosine A1-receptor blockade and vagotomy on the gasping and heart rate response to hypoxia in rats during early postnatal maturation

2007 ◽  
Vol 103 (4) ◽  
pp. 1234-1241 ◽  
Author(s):  
James E. Fewell ◽  
Chunfen Zhang ◽  
Anne M. Gillis
Keyword(s):  
Heart Rate ◽  
Heart Rate Response ◽  
Parasympathetic Nervous System ◽  
Age Groups ◽  
Sudden Infant Death ◽  
Severe Hypoxia ◽  
Sudden Infant ◽  
Postnatal Life ◽  
Postnatal Maturation ◽  
Rat Pups

Failure to autoresuscitate from apnea has been suggested to play a role in sudden infant death. Little is known, however, about factors that influence the gasping and heart rate response to severe hypoxia that are fundamental to successful autoresuscitation in the newborn. The present experiments were carried out on 184 rat pups to investigate the influence of the parasympathetic nervous system, as well as adenosine, in mediating the profound bradycardia that occurs with the onset of hypoxic-induced primary apnea and in modulating hypoxic gasping. On days 1 to 2, days 5 to 6, and days 10 to 11 postpartum and following bilateral cervical vagotomy (VAG) or administration of a selective adenosine A1 receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine; DPCPX), each pup was exposed to a single period of severe hypoxia produced by breathing an anoxic gas mixture (97% N2-3% CO2). Exposure to severe hypoxia resulted in an age-dependent decrease in heart rate ( P < 0.001), accentuated with increasing postnatal age, that was attenuated in all age groups by DPCPX but not by VAG. Furthermore, DPCPX but not VAG decreased the time to last gasp but increased the total number of gasps in the 1- to 2-day-old and 5- to 6-day-old pups but not in the 10- to 11-day-old pups during exposure to severe hypoxia. Thus our data provide evidence that adenosine acting via adenosine A1 receptors plays a role in modulating hypoxic gasping and in mediating the profound bradycardia that occurs coincident with hypoxic-induced primary apnea in rats during early postnatal life.

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