Brain Tryptophan Hydroxylation: Dependence on Arterial Oxygen Tension

Davis, James N.; Carlsson, Arvid; MacMillan, V.; Siesjö, Bo K.

doi:10.1126/science.182.4107.72

Cited by 117 publications

(45 citation statements)

References 14 publications

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“…As short as 30 min of CH decreased TPH activity in many brain regions in neonatal and adult rats (13,40). On the other hand, prolonged exposures to CH affected TPH activity in the brain in a region-dependent manner.…”

Section: Effects Of Hypoxia On 5-ht Synthesismentioning

confidence: 88%

Hypoxia. 3. Hypoxia and neurotransmitter synthesis

Kumar

2011

American Journal of Physiology-Cell Physiology

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Central and peripheral neurons as well as neuroendocrine cells express a variety of neurotransmitters/modulators that play critical roles in regulation of physiological systems. The synthesis of several neurotransmitters/ modulators is regulated by O2-requiring rate-limiting enzymes. Consequently, hypoxia resulting from perturbations in O2 homeostasis can affect neuronal functions by altering neurotransmitter synthesis. Two broad categories of hypoxia are frequently encountered: continuous hypoxia (CH) and intermittent hypoxia (IH). CH is often seen during high altitude sojourns, whereas IH is experienced in sleep-disordered breathing with recurrent apneas (i.e., brief, repetitive cessations of breathing). This article presents what is currently known on the effects of both forms of hypoxia on neurotransmitter levels and neurotransmitter synthesizing enzymes in the central and peripheral nervous systems. biogenic amines; bioactive peptides; glutamate; ␥-amino butyric acid; gasotransmitters THE MAMMALIAN BRAIN represents 2% of the total body weight and consumes 20% of the total body oxygen for its normal function (108). This high level of oxygen consumption makes the brain an extremely sensitive tissue to changes in arterial blood oxygen levels. Many physiological systems are regulated by the nervous system, and neurotransmitters are critical for neuronal function. The rate-limiting enzymes associated with the synthesis of several neurotransmitters require molecular oxygen for their activity. Consequently, hypoxia (i.e., reduced oxygen availability) resulting from perturbations in O 2 homeostasis can profoundly impact neurotransmitter synthesis resulting in altered neuronal functions and consequently impact physiological systems.Hypoxia is experienced in a variety of physiological and pathological conditions. Two broad categories of hypoxia are most frequently encountered; continuous hypoxia (CH) and intermittent hypoxia (IH). For instance, CH is experienced by healthy humans during high altitude sojourns, whereas IH is encountered during sleep-disordered breathing with recurrent apneas; i.e., brief repetitive cessations of breathing wherein each episode lasts for tens of seconds. The purpose of this article is to provide a brief review of the effects of both forms of hypoxia on neurotransmitter levels, rate-limiting enzymes associated with neurotransmitter synthesis and the underlying mechanisms. Several of these molecules, which function as transmitters/modulators in the nervous system, are also expressed in nonneuronal tissues. However, because of space constraints, this review will focus on the effects of hypoxia on neurotransmitters in the central and peripheral nervous systems.Based on the chemical properties, neurotransmitters are divided into various groups as shown in Table 1. This review focuses on the impact of CH and IH on the synthesis of biogenic amines, acetylcholine, excitatory and inhibitory amino acids, bioactive peptides, and gasotransmitters (for examples see Table 1). BIOGENIC AMINESBiogenic ...

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Section: Effects Of Hypoxia On 5-ht Synthesismentioning

confidence: 88%

Hypoxia. 3. Hypoxia and neurotransmitter synthesis

Kumar

2011

American Journal of Physiology-Cell Physiology

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“…Chronic exposure to hypobaric hypoxia (2 weeks at 25,000 ft) significantly reduced serotonin in frontal cortex and brainstem in both male and female rats (Ray et al, 2011), while acute hypoxia (24 h at 22,960 ft) depleted serotonin in the male rat striatum and hypothalamus by 34% (Prioux-Guyonneau et al, 1982). Tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, requires molecular oxygen for its activity (Fitzpatrick, 1999), and is extremely vulnerable to hypoxia (Davis et al, 1973;Vaccari et al, 1978), potentially lowering brain serotonin synthesis in hypoxia. Hypoxia alters activity of both synthetic and catabolic enzymes in the noradrenergic pathway (Gozal et al, 2005;Vaccari et al, 1978), potentially changing brain dopamine and norepinephrine levels as well (Kumar, 2011).…”

Section: Discussionmentioning

confidence: 99%

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Kanekar

Bogdanova

Olson

et al. 2015

High Altitude Medicine & Biology

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Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52-60, 2015-Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males.

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“…After an hypoxic episode, an increased availability of monoamine precursors and an increased rate of monoamine synthesis prevails (39). This suggests that in growth-retarded individuals the intrauterine hypoxia will reduce the activity of the highly hypoxiasensitive, rate-limiting enzymes of monoamine synthesis (40) and slow the cerebral metabolic rate (10). The trophic influences of monoamines, particularly serotonin, on cerebral growth (4 1) will be diminished and cerebral growth retardation will result.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Tolerance of Hypoxia in Growth-Retarded and Appropriately Grown Newborn Guinea Pigs

Thordstein

Kjellmer

1988

Pediatr Res

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ABSTRACT. To elucidate if there is a reduced perinatalPao2, oxygen tension of arterial blood tolerance of hypoxia in growth retardation and approach CMR02, cerebral metabolic rate of oxygen its pathophysiologic background, newborn guinea pigs of different weights were subjected to standardized hypoxia. Intrauterine growth retardation was induced through uterine artery ligation. After spontaneous delivery experiments were performed within 2 days. After stabilization, hypoxia of stepwise increased severity was instituted. Blood gases, metabolic, cardiovascular, and neurophysiologic [somatosensory-evoked potentials (SEP)] parameters were monitored. A control series in which equally large blood samples were taken at the same intervals was performed. The animals were grouped according to birth weight: 2101 g (n = 10,12), 71-100 g (n = 11, lo), and 570 g (n = 8,3) (hypoxic and control series, respectively). Basal SEP latencies did not differ between the groups. Under hypoxia, both the amplitude of the SEP and the time to complete loss of the SEP was reduced in proportion to the degree of growth retardation. The differences between all groups were significant. The animals in the control series did not change their SEP performance significantly. Slight differences in metabolic and cardiovascular parameters between the groups were found not likely to explain the differences in SEP performance. Therefore, it is concluded that a reduced cerebral tolerance of hypoxia prevails in growthretarded newborn guinea pigs and that this is related to changes in the brain itself. It is also concluded that a relations hi^ exists between the degree of growth retardation and tiat of reduced cerebral ~ypoxiautolerance. (Pediatr Res 24: 633-638, 1988) IUGR resulting in neonates who are SGA remains a major problem in modern perinatal care. Fetuses and neonates who are SGA are overrepresented in clinical materials of children with neurodevelopmental handicaps (1-5) and have a several-fold increased risk of perinatal asphyxia (6, 7) compared to fetuses and neonates who are AGA. It is uncertain if there is also a reduced tolerance of asphyxia in SGA individuals, the underlying pathophysiologic background of which is obscure. Possible explanations are disturbed metabolic (8, 9) or cardiovascular (10) function. Alterations indicating a change in central nervous function have also been noted, suggesting that the reason might reside in the brain itself (1 1-1 5).In countries where malnutrition is uncommon, the majority of IUGR cases is caused by various conditions leading to placental vascular insufficiency with impaired exchange of gases and nutrients over the placenta (16). The aim of this study was to monitor metabolic, cardiovascular, and cerebral function under standardized, progressive hypoxia in newborn guinea pigs with different degrees of IUGR, produced by placental vascular insufficiency. This would make it possible to investigate if there is a reduced perinatal tolerance of hypoxia in growth retarded individuals and if so, approach i...

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Brain Tryptophan Hydroxylation: Dependence on Arterial Oxygen Tension

Cited by 117 publications

References 14 publications

Hypoxia. 3. Hypoxia and neurotransmitter synthesis

Hypoxia. 3. Hypoxia and neurotransmitter synthesis

Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

Cerebral Tolerance of Hypoxia in Growth-Retarded and Appropriately Grown Newborn Guinea Pigs

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