Tyrosine hydroxylase protein content in the medulla oblongata of the foetal sheep brain increases in response to acute but not chronic hypoxia

Adams, Michael Brenton; Brown, Rosemary; Gibson, Catherine; Coulter, Catherine; McMillen, I. C.

doi:10.1016/s0304-3940(01)02381-3

Cited by 11 publications

(11 citation statements)

References 18 publications

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“…of this brain region in respiratory and cardiovascular control. Indeed, several studies have identified increases in TH expression in specific substructures of the brain stem after SH exposure, more specifically in those regions involved in respiratory and baroreflex activity (1,43,46). However, our data show no change in TH expression or phosphorylation in brain stem, whereas in the cortex, posttranslational modifications and changes in TH activation occurred in SH but not in IH.…”

Section: Discussioncontrasting

confidence: 73%

Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia

Gozal¹,

Shah²,

Péquignot³

et al. 2005

Journal of Applied Physiology

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Tyrosine hydroxylase, a hypoxia-regulated gene, may be involved in tissue adaptation to hypoxia. Intermittent hypoxia, a characteristic feature of sleep apnea, leads to significant memory deficits, as well as to cortex and hippocampal apoptosis that are absent after sustained hypoxia. To examine the hypothesis that sustained and intermittent hypoxia induce different catecholaminergic responses, changes in tyrosine hydroxylase mRNA, protein expression, and activity were compared in various brain regions of male rats exposed for 6 h, 1 day, 3 days, and 7 days to sustained hypoxia (10% O(2)), intermittent hypoxia (alternating room air and 10% O(2)), or normoxia. Tyrosine hydroxylase activity, measured at 7 days, increased in the cortex as follows: sustained > intermittent > normoxia. Furthermore, activity decreased in the brain stem and was unchanged in other brain regions of sustained hypoxia-exposed rats, as well as in all regions from animals exposed to intermittent hypoxia, suggesting stimulus-specific and heterotopic catecholamine regulation. In the cortex, tyrosine hydroxylase mRNA expression was increased, whereas protein expression remained unchanged. In addition, significant differences in the time course of cortical Ser(40) tyrosine hydroxylase phosphorylation were present in the cortex, suggesting that intermittent and sustained hypoxia-induced enzymatic activity differences are related to different phosphorylation patterns. We conclude that long-term hypoxia induces site-specific changes in tyrosine hydroxylase activity and that intermittent hypoxia elicits reduced tyrosine hydroxylase recruitment and phosphorylation compared with sustained hypoxia. Such changes may not only account for differences in enzyme activity but also suggest that, with differential regional brain susceptibility to hypoxia, recruitment of different mechanisms in response to hypoxia will elicit region-specific modulation of catecholamine response.

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Section: Discussioncontrasting

confidence: 73%

Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia

Gozal¹,

Shah²,

Péquignot³

et al. 2005

Journal of Applied Physiology

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“…Even in the ATF‐2 –/– mice at E18.5, the increase in the TH immunoreactivity in medulla oblongata likely are not due to hypoxia for the following reasons. Although acute hypoxia reportedly induced TH expression in adrenal or cultured cells, including PC12 cells, several previous studies demonstrated prenatal hypoxic conditions at embryonic stages led to no increase in the TH expression in medulla (White and Lawson, 1997; Adams et al, 2001). When pregnant rats were placed in moderate hypoxia from E18 until birth, pups had lower levels of TH mRNA and protein at birth in the dorsal medulla (White and Lawson, 1997).…”

Section: Discussionmentioning

confidence: 94%

“…When pregnant rats were placed in moderate hypoxia from E18 until birth, pups had lower levels of TH mRNA and protein at birth in the dorsal medulla (White and Lawson, 1997). In addition, placenta restriction in sheep during late embryonic days caused no change in the level of TH protein in medulla oblongata (Adams et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of tyrosine hydroxylase and anomalous neurites in catecholaminergic neurons of ATF‐2 null mice

Kojima¹,

Suzuki²,

Maekawa³

et al. 2007

J of Neuroscience Research

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ATF-2/CRE-BP1 was originally identified as a cAMP-responsive element (CRE) binding protein abundant in the brain. We previously reported that phosphorylation of ATF-2 increased the expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme for catecholamine biosynthesis, directly acting on the CRE in the promoter region of the TH gene in PC12D cells (Suzuki et al. [2002] J. Biol. Chem. 277:40768-40774). To examine the role of ATF-2 on transcriptional control of the TH gene in the brain, we investigated the TH expression in ATF-2-/- mice. We found that TH expression was greatly increased in medulla oblongata and locus ceruleus of the ATF-2-deficient embryos. Ectopic expression of TH was observed in the raphe magnus nucleus, where serotonergic neural cell bodies are located. Interestingly, A10 dorsal neurons were lost in the embryos of ATF-2-/- mice. There was no difference in the TH immunoreactivity in the olfactory bulb. The data showed that alteration in TH expression by absence of ATF-2 gradually declined from caudal to rostral part of the brain. We also found anomalous neurite extension in catecholaminergic neurons of ATF-2 null mice, i.e., increased dendritic arborization and shortened axons. These data suggest that ATF-2 plays critical roles for proper expression of the TH gene and for neurite extension of catecholaminergic neurons, possibly through a repressor-like action.

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“…In fetal lambs, decreasing the maternal inspired fraction of O 2 to 12–13 % ( P O2 around 90–100 mmHg – similar to what is found in major high altitude cities) for 28 days decreases fetal arterial P O2 from 29.7 to 19.1 mmHg (Kitanaka et al 1989). In a model of acute hypoxia in fetal sheep, lowering the inspired fraction of oxygen to 8 % ( P O2 around 60 mmHg) decreases fetal arterial P O2 from 23.8 to 14.6 mmHg (Adams et al 2001). The level of hypoxia used in our model (10 % O 2 or P O2 around 75–80 mmHg) should therefore reduce fetal arterial P O2 to levels between 20 and 15 mmHg, i.e.…”

Section: Discussionmentioning

confidence: 99%

Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats

Joseph

Mamet

Lee

et al. 2002

The Journal of Physiology

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METHODSAll experiments were carried out according to the ethical principles laid down by the French (Ministére de l'Agriculture) and EU Council directives for care of laboratory animals (No. 02889). At the end of the experiments, all animals were killed by exposure to a rising concentration of CO 2 . All the animals used in this study were sibling pups from a previously published study (Mamet et al. 2002). Gestational hypoxiaSixty pregnant Sprague-Dawley rats (IFFA-CREDO, l'Arbresle, France) were housed in a temperature-controlled room (26 ± 1°C) with a 12/12 light/dark cycle and allowed free access to food and water. The first day of gestation was determined on the basis of a vaginal smear. Pregnant rats were first exposed to hypoxia on the fifth day of gestation so as not to disturb implantation of the embryos. From the 5th to 20th day of gestation, the experimental group was housed in a Plexiglas chamber, with a normobaric hypoxic atmosphere consisting of 10 % O 2 -90 % N 2 . The O 2 and CO 2 contents of this atmosphere were monitored twice daily using Servomex analysers (Servomex Co., Norwood, MA, USA). The CO 2 expired by the rats was eliminated by circulating the atmosphere through soda lime, so that the atmospheric content of this gas never exceeded 0.1 %. The water contained in the expired gas was trapped in a chilled glass tank. On the 20th day of gestation, hypoxic pregnant rats were returned to normoxia (21 % O 2 ), under which they gave birth. Immediately after birth, the male pups were grouped together, and then randomly redistributed to nursing females (n = 60) which had never been exposed to hypoxic conditions (10-12 pups per female). This procedure was followed to avoid sex differences, eliminate variations between litters, ensure a standard nutritional status, and avoid any possible effect of hypoxia on the nutritional quality of the milk. These offspring were designated as the prenatal hypoxic (PNH) group. Pups from another 60 pregnant Sprague-Dawley rats, whose gestation occurred under normoxic conditions (21 % O 2 ), but were otherwise treated in the same manner and placed in a similar Plexiglas chamber, were designated as the control (cont) group.

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Tyrosine hydroxylase protein content in the medulla oblongata of the foetal sheep brain increases in response to acute but not chronic hypoxia

Cited by 11 publications

References 18 publications

Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia

Tyrosine hydroxylase expression and activity in the rat brain: differential regulation after long-term intermittent or sustained hypoxia

Increased expression of tyrosine hydroxylase and anomalous neurites in catecholaminergic neurons of ATF‐2 null mice

Prenatal hypoxia impairs circadian synchronisation and response of the biological clock to light in adult rats

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