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T Hertzberg

Publications and source records attributed to T Hertzberg.

At least 19 recordsLinked to original sources
PubMed1995

Depolarizing stimuli induce high levels of dopamine synthesis in fetal rat sensory neurons.

To investigate the role of activity-dependent mechanisms in sensory transmitter development, we examined the effect of depolarizing stimuli on tyrosine hydroxylase expression and dopamine synthesis in cells of the fetal rat petrosal ganglion, a model of catecholaminergic sensory neurons. Although dopaminergic traits are normally detectable in only 10-20% of ganglion neurones, exposure to depolarizing concentrations of potassium chloride (40 mM) or veratridine (10 microM) in culture induced tyrosine hydroxylase expression in 100% of petrosal neurons and a 10-fold increase in dopamine content. Tyrosine hydroxylase expression remained elevated in a subset of neurons following return to control conditions, suggesting that chronic depolarization elicits a phenotypic switch in some cells. These data show for the first time that transmitter expression in developing sensory neurons can be regulated by activity-related cues.

Animals↗
PubMed1995

Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome.

The drive on respiration mediated by the peripheral arterial chemoreceptors was assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/- 8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine exposure, an effect counteracted by blockade of peripheral dopamine type 2 receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and increased the expression of tyrosine hydroxylase (TH) in the carotid bodies, further suggesting that DA mediates the acute effect of nicotine on arterial chemoreceptor function. During postnatal development TH and DA2R mRNA levels in the carotid bodies decreased. Thus, nicotine from smoking may also interfere with the postnatal resetting of the oxygen sensitivity of the peripheral arterial chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this period. Collectively these effects of nicotine on the peripheral arterial chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate the protective chemoreflex response. These mechanisms may underlie the well-known relation between maternal smoking and sudden infant death syndrome.

Animals↗
PubMed1994

BDNF supports mammalian chemoafferent neurons in vitro and following peripheral target removal in vivo.

Chemoreceptor neurons innervating the rat carotid body were used as a model system to define target regulation of visceral sensory development in fetal and newborn animals. In vitro, chemoafferents were selectively supported by coculture with the carotid body or by treatment with trkB ligands [brain-derived neurotrophic factor (BDNF) and neurotrophin-4], whereas nerve growth factor and neurotrophin 3 had no effect. In vivo, chemoafferent neurons died following carotid body removal at birth, indicating a predominant role of peripheral, rather than central, targets in mediating survival at this stage. However, in the absence of target tissues, a large proportion of carotid body afferents could be rescued by implants containing BDNF. Moreover, BDNF mRNA was detected in the newborn carotid body by reverse transcriptase polymerase chain reaction. These data provide the first demonstration that BDNF can substitute for peripheral target support of sensory neuron survival in vivo and indicate that trkB ligands may be particularly important for development of visceral afferents involved in cardiorespiratory control.

Afferent Pathways↗
PubMed1994

Birth-related changes of expression and turnover of some neuroactive agents and respiratory control.

Respiratory movements are partially inhibited before birth and central and peripheral chemoreceptors are probably less sensitive. The transition to continuous breathing might be due to the switch-off of inhibitory neuromodulators and the switch-on of excitatory neuroactive agents. This hypothesis has been explored mainly in rats. One example is dopamine which was found to have a high turnover in carotid bodies in newborn pups prior to decreasing rapidly. It is suggested to inhibit the carotid bodies before birth. In the brain, the noradrenergic system has been found to be activated at birth, possibly promoting neural transmission and arousal. Increased expressions of mRNA for c-fos, tyrosine hydroxylase and some neuropeptides have also been found.

Animals↗
PubMed1992

Ventilatory response to hyperoxia in newborn rats born in hypoxia--possible relationship to carotid body dopamine.

1. The influence of postnatal hypoxia on regulation of breathing and turnover rate of carotid body dopamine was examined in newborn rats. The percentage change in frequency, tidal volume and ventilation elicited by transient hyperoxia was assessed by flow plethysmography in unanaesthetized pups. The alteration in ventilation was taken as an index of peripheral chemoreceptor activity. 2. The rats were born and reared in hypoxia. The inspired oxygen fraction (FI,O2) was 0.12-0.14 until 2 days after delivery when the rats were placed into room air and the ventilatory chemoreflex was tested. At 4 days of age, i.e. 2 days after termination of hypoxia, the rats were tested again. The ventilatory data were compared with those from a previous study in normoxic rats. 3. We found a smaller decrease in ventilation (8.8 +/- 3.9%, mean +/- S.D.) in the hypoxic rats at 2 days of age compared with normoxic rats (22.7 +/- 6.4%; P < 0.001). In contrast, at 4 days of age there was no difference in ventilatory response between the posthypoxic rats (19.2 +/- 4.6%) and normoxic pups (18.6 +/- 4.9%). 4. The turnover rates of dopamine in carotid bodies were determined at 0-6, 6-12, 12-24 h and 2 days after birth in hypoxic rats and in 2-day-old posthypoxic rat pups at different time intervals after termination of hypoxia. Postnatal hypoxia sustained a high turnover rate which decreased after termination of the hypoxia. 5. We propose that the weak chemoreflex in hypoxic rat pups is brought about by a high release of carotid body dopamine.

Animals↗
PubMed1991

CO2-sensitivity in newborn and young infants tested by the rebreathing method. Methodological aspects.

The rebreathing method in newborn and young infants was tested with regard to the effects of increasing levels of CO2 on the behavioral state and to the influence of facial stimulation caused by the use of a face mask and pneumotachograph on the breathing pattern. Successive increases in inspired CO2 levels from 3 to 8.5% did not change the behavioral state. The application or removal of a face mask, with or without an attached pneumotachograph, caused an immediate disruption in the breathing pattern which lasted 10-40 s. Thereafter, breathing stabilized. When only the face mask was used, the increases in minute ventilation, tidal volume and cycle duration of 7, 13 and 5%, respectively, were transient and lasted for 40-50 breaths. The breathing then returned to control levels. In contrast, breathing through the face mask connected to the pneumotachograph caused a long-lasting increase in ventilation (12%) due to the retention of CO2 in the spirometric circuit. We conclude that the inhalation of a continuously increasing mixture of 3-8.5% CO2 in O2 did not influence the behavioral state and that the effect of face mask on breathing pattern was transient.

Carbon Dioxide↗
PubMed1991

Changes in levels of mRNA coding for catecholamine synthesizing enzymes and neuropeptide Y in the adrenal medulla of the newborn rat.

We have measured levels of mRNA coding for the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), phenylethanolamine N-methyltransferase (PNMT) and for neuropeptide Y (NPY) in rat adrenal medulla by using in situ hybridization histochemistry. Ages of one day before birth (E21), 12 h, 24 h, 2 days and 4 days after birth and in adults were studied. TH, D beta H and NPY mRNA levels increased markedly postnatally. Twelve hours after birth the levels of mRNA for TH, D beta H and NPY were, respectively, 512 +/- 18%, 370 +/- 24% and 253 +/- 21% of E21 levels. At 24 h of age NPY mRNA level was 437 +/- 73% of fetal value. In contrast, the levels of mRNA coding for PNMT increased more slowly and reached 196 +/- 9% of E21 level on postnatal day four and was further increased in adult rats.

Adrenal Medulla↗
PubMed1990

Development of the arterial chemoreflex and turnover of carotid body catecholamines in the newborn rat.

1. The peripheral, arterial chemoreceptors in the carotid body are active and responsive in the fetus. At birth, when oxygenation increases, the chemoreceptors are silenced. Over the next few days the sensitivity is reset toward the adult level and the chemoreceptors influence breathing during normal conditions. In order to investigate the underlying mechanisms of this resetting we examined the strength of the chemoreflex in newborn rats and correlated this to the contents of dopamine and noradrenaline in the carotid bodies of the newborn pups and near-term fetuses. Furthermore, turnover rates of dopamine and noradrenaline were determined in newborn rats up to 1 week of age by analysis of catecholamine decreases after inhibition of synthesis with alpha-methyl-p-tyrosine. 2. Chemoreceptor influence was assessed by the method of 'physiological chemodenervation' with hyperoxia of 15-20 s duration in unanaesthetized rat pups. Relative changes in ventilation elicited by hyperoxia were determined by body plethysmography. We found no change in ventilation on the day of birth either in vaginally born rats or in near-term pups delivered by Caesarean section. After 1 day there was a significant decrease in ventilation of -19.4 +/- 2.3% (mean +/- S.E.M.) and at 7 days of age the decrease was -28.8 +/- 2.2%, suggesting an increasing influence from the peripheral chemoreceptors. 3. The contents of dopamine and noradrenaline were measured by high-performance liquid chromatography. Dopamine increased from 3.7 +/- 0.4 pmol (pair of carotid bodies)-1 in the fetus to a peak of 15.9 +/- 2.6, 6-12 h after birth followed by a decline to 7.1 +/- 0.7 at 7 days of age. Noradrenaline levels increased from 1.3 +/- 0.3 in the fetus to 9.6 +/- 1.1 pmol (pair of carotid bodies)-1 after 4 days. The turnover rate of dopamine decreased from 4.4 pmol (pair of carotid bodies)-1 h-1 0-6 h after birth to 1.0 at 6-12 h of age. The turnover rate of noradrenaline also decreased over the first hours following delivery. 4. Since dopamine is an inhibitory neuromodulator in this system, we suggest that the increase in sensitivity seen after the first day of life is, at least in part, due to a decrease in the release of dopamine and thus a removal of an inhibitory mechanism.

Animals↗
PubMed1989

Respiratory and arousal responses to hypoxia in apnoeic infants reinvestigated.

Respiratory and arousal responses to mild hypoxia (15% oxygen in nitrogen) were recorded in 18 healthy infants and 33 infants who had sustained severe sleep related apnoeic events (ALTE). Respiratory movements and transcutaneous gas pressures (tcPO2 and tcPCO2) were continuously monitored during the 10 min test. The changes in tcPCO2 in relation to the decrease in tcPO2 were used as an index of the ventilatory and metabolic responses to hypoxia. We found that the response of apnoeic infants was within the range of the controls although the distribution of the individual response slopes was shifted towards the lower end of the range. Arousal was observed in 33% of apnoeic infants and 32% of the controls. Regular periodic breathing occurred in 42% of apnoeic infants compared to 28% of controls. In contrast to the controls, periodic breathing in apnoeic infants was not associated with a drop in tcPCO2 to below baseline levels. Apnoeic infants also alternated between regular and periodic breathing during the test. These findings are suggestive of a weak feed back control of breathing but do not support former views of a deficient hypoxic response in infants with ALTE.

Arousal↗
PubMed1989

Hypoxia reinforces laryngeal reflex bradycardia in infants.

The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome.

Blood Gas Monitoring, Transcutaneous↗
PubMed1989

Adenosine concentration in umbilical cord blood of newborn infants after vaginal delivery and cesarean section.

Umbilical blood was collected immediately at birth (less than 30 s) in full-term infants after vaginal deliveries (n = 33) and elective cesarean sections (n = 11). Blood gases, plasma adenosine, hypoxanthine, and catecholamine concentrations were determined. In vaginally born infants the median arterial adenosine concentration was found to be 0.46 microM (range 0.13-2.06) and the venous 0.48 microM (0.09-1.62). These levels were significantly higher (p less than 0.01) than in infants delivered by elective cesarean section; 0.16 microM (0.04-0.42) in the artery and 0.17 microM (0.02-0.56) in the vein. Vaginally born infants showed about a 4-fold higher level of umbilical arterial catecholamines than infants born by elective cesarean section. There was a strong inverse correlation between arterial hypoxanthine concentration and pH (r = -0.81, p less than 0.01). It is suggested that increased adenosine release at vaginal delivery modulates the stress response elicited by the strong catecholamine surge and may furthermore exert protective effects in perinatal asphyxia.

Adenosine↗
PubMed1987

Postnatal sensitivity of the peripheral chemoreceptors in newborn infants.

The peripheral chemoreflex was tested in healthy term infants by measuring the ventilatory response to 100% oxygen over 30 seconds. Minute ventilation did not change when studied two to six hours after birth. By contrast, at 2-6 days of age a mean decrease of 9.8% was noted, the difference between the groups being highly significant. There were no significant changes in respiratory rate. It is concluded that the chemoreflex is less active immediately after birth than it is a few days later, possibly due to a resetting of the sensitivity of the peripheral chemoreceptors from the fetal state, with its relatively low arterial oxygen tension to the higher postnatal concentrations.

Chemoreceptor Cells↗
PubMed1987

Ventilatory and metabolic responses to acute hypoxia in infants assessed by transcutaneous gas monitoring.

Transcutaneous PO2, transcutaneous PCO2 and respiratory pattern were monitored during acute mild hypoxia (15% O2) in quiet sleep. Eighteen healthy infants were studied sequentially at 1-5 days, 4-8 weeks and 10-14 weeks of age. The transcutaneous PCO2 changes (delta PCO2) related to the transcutaneous PO2 fall, were used as an index of the total ventilatory and metabolic response during the test. This calculated index was related to the occurrence of arousal and periodic breathing. Transcutaneous PCO2 increased above control levels in infants 1-5 days old, decreased markedly in infants 4-8 weeks of age, and decreased slightly or remained unchanged in the 10-14 weeks old infants. The changes in response pattern were significant (P less than 0.006). These differences in response were not reflected in the lowest values of transcutaneous PO2 attained during the test. The lowest transcutaneous PO2 levels did not differ significantly between the age groups, indicating that the mechanisms maintaining PO2 during hypoxia may change during development. Periodic breathing was always associated with a decrease in transcutaneous PCO2 and in 8 out of 10 tests where it occurred it commenced at the lowest transcutaneous PCO2 level recorded. These results do not support the concept that periodic breathing is a sign of hypoventilation. Arousal was observed in less than half of the infants and was not related to the degree of hypoxaemia. We conclude that hypoxic arousal in infants may not be the important escape mechanism as suggested previously.

Arousal↗