Tyrosine availability and brain noradrenaline synthesis in the fetus: control by maternal tyrosine ingestion

Garabal, Mileine; Arevalo, R.; Díaz-Palarea, M.D.; Castro, Rafael; Rodrı́guez, Manuel

doi:10.1016/0006-8993(88)90703-2

Cited by 17 publications

(4 citation statements)

References 45 publications

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“…As previously mentioned, the two identified entraining signals are rhythmic food ingestion and timed injections of melatonin (6,7). The rhythmic ingestion of food by the mother could provide a rhythmic precursor pool of tyrosine, driving rhythmic fetal brain dopamine production (21,22); maternally derived melatonin could directly modulate the release of dopamine in the fetal SCN, as demonstrated in other systems (23,24). Melatonin receptors are expressed in the fetal SCN (25,26).…”

Section: Discussionmentioning

confidence: 97%

D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei.

Weaver

Rivkees

Reppert

1992

Proc. Natl. Acad. Sci. U.S.A.

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The existence of an activatable dopamine system within the hypothalamic suprachiasmatic nuclei (SCN), the site of a biological clock, was investigated in rats during fetal life. In situ hybridization studies revealed that DIdopamine receptor mRNA was highly expressed in the fetal SCN and not expressed in other hypothalamic regions. Cocaine inected into pregnant rats or directly into rat fetuses on day 20 of gestation selectively activated c-fos gene expression in the fetal SCN; cocaine did not induce c-fos expression elsewhere in the fetal brain or in the maternal SCN. This cocaine-induced activation of c-fos expression in fetal SCN was mediated in part through D1-dopamine receptors, as the cocaine-induced activation was partially blocked by the D1-dopamine receptor antagonist SCH 23390. In addition, the selective DI-dopamine receptor agonist SKF 38393 induced high levels of c-fos expression in the fetal SCN. The presence of an activatable dopamine system within the fetal SCN provides a mechanism through which maternal signals could entrain the fetal biological clock and through which maternally administered psychotropic drugs could alter normal development of the circadian timing system. The hypothalamic suprachiasmatic nuclei (SCN) function as a biological clock that generates circadian rhythms in mammals (1-3). Retinal pathways transmit sensory information about the daily light-dark cycle from the eye to the SCN. This photic information entrains the biological clock so that circadian rhythms are expressed in proper relationship to each other and the 24-hr day. An entrained biological clock plays a major role in optimizing the efficiency of biological systems and better prepares the body to cope with stress, injury, and disease.In fetal rats, the SCN are functioning as a biological clock soon after SCN neurons have migrated to their final cellular position (4,5). At this stage of development, retinal pathways to the SCN have not yet matured. Instead, the mother transduces photic information into circadian signals that entrain the timing (phase) of the fetal biological clock to prevailing environmental light-dark conditions. It appears that multiple maternal signals are capable of entraining the fetus and that these signals normally operate in concert (4, 5). Specifically, periodic feeding can entrain the fetuses of SCN-lesioned pregnant rats (6), and pharmacological doses of the pineal hormone melatonin can entrain the fetuses of SCN-lesioned pregnant hamsters (7). Unknown are the cellular and molecular mechanism(s) through which these signals normally act to entrain the fetal SCN.As part of our ongoing efforts to delineate functionally relevant neurotransmitter systems within the fetal SCN that may participate in maternal-fetal entrainment, we discovered a high level of D1-dopamine receptor gene expression in the biological clock offetal rats. We further report that activation of D1-dopamine Antisense and sense complementary RNA (cRNA) probes were generated by digestion of plasmids with the appropri...

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Section: Discussionmentioning

confidence: 97%

D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei.

Weaver

Rivkees

Reppert

1992

Proc. Natl. Acad. Sci. U.S.A.

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“…However, studies of central catecholaminergic mechanisms suggest that abnormal nutritional status has a substantial deleterious effect on neuronal and synaptic function. During dietary restriction, norepinephrine levels and some indices of neuronal activity show moderate degrees of attenuation (4)(5)(6)(7)(8); although whole brain norepinephrine levels tend to be restored to normal in adulthood (9-1 I), there are at least two reports that deficits in receptor binding sites and synaptic activity may persist if malnutrition is maintained into adulthood (12,13).…”

mentioning

confidence: 99%

Undernutrition and Overnutrition in the Neonatal Rat: Long-Term Effects on Noradrenergic Pathways in Brain Regions

1990

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ABSTRACT. To determine whether neonatal nutrition influences development of CNS noradrenergic systems, litter sizes were manipulated at birth to produce undernutrition (16-17 pupsllitter) or overnutrition (five to six pups) and compared to rats reared in normal litter sizes (10-11 pups). Studies were conducted throughout the preweaning period in which nutrition was manipulated, as well as during postweaning nutritional rehabilitation. Sparing of brain growth occurred, evidenced by much smaller changes in brain region wt than in body wt. Similarly, neonatal malnutrition produced major deficits in norepinephrine levels in peripheral sympathetic pathways, but levels in the brain remained within normal limits. Development of 13H]norepinephrine synaptosomal uptake, a biochemical index for presynaptic terminals, was unimpaired by malnutrition; indeed, higher uptake values were seen than in the control population. Nevertheless, norepinephrine turnover was severely attenuated during nutritional restriction and the effect persisted into adulthood; the deficit was greater in the cerebral cortex than in the cerebellum, despite the fact that cerebellar growth showed less sparing. Development of binding capabilities of noradrenergic receptors, particularly the a.2-and @-subtypes, were also adversely affected in cerebral cortex, again suggestive of a deleterious effect on synaptic function. Animals exposed to neonatal overnutrition showed only slight effects on brain region wt or norepinephrine levels, but did display some suppression of [3H]norepinephrine synaptosomal uptake and enhancement of norepinephrine turnover; changes in receptor binding capabilities in the overnourished animals were attributable to the small alterations in brain region wt. These data indicate that neonatal nutrition alters presynaptic and postsynaptic markers of noradrenergic function that remain abnormal even when nutritional rehabilitation occurs. (Pediatr Res 27: 191-197, 1990) Abbreviation ANOVA, analysis of variance The role of prenatal and postnatal nutrition in maintenance of normal growth and development is an issue of intense interest. A variety of studies on animal models of early malnutrition has demonstrated the phenomenon of "brain sparing," wherein the CNS undergoes substantially less growth impairment and struc- Supported by USPHS HD-097 13.tural disruption than does the rest of the organism (1-3). However, studies of central catecholaminergic mechanisms suggest that abnormal nutritional status has a substantial deleterious effect on neuronal and synaptic function. During dietary restriction, norepinephrine levels and some indices of neuronal activity show moderate degrees of attenuation (4-8); although whole brain norepinephrine levels tend to be restored to normal in adulthood (9-1 I), there are at least two reports that deficits in receptor binding sites and synaptic activity may persist if malnutrition is maintained into adulthood (12, 13). Recent work on factors other than nutrition has demonptrated the existence of critical p...

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“…In contrast, it would be predicted that synthesis of tyrosine-derived neurotransmitters would be increased in materal tyrosinaemia. This proposal is supported by animal studies which show elevated brain noradrenaline levels during maternal tyrosine supplementation [10], although increased tyrosine levels to appear to impair certain other neuro-endocrine functions [22]. Our patient's poor compliance with oral amino acid supplements prior to pregnancy could have posed additional dangers; she was able to avoid symptoms by restricting dietary protein intake to a level where plasma concentrations of most amino acids were close to or below the lower limit of normal range.…”

Section: Discussionmentioning

confidence: 78%

Maternal tyrosinaemia II: Management and successful outcome

1992

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A 25-year-old woman with tyrosinaemia type II was treated from the 5th week of pregnancy with a protein-restricted diet supplemented with a tyrosine/phenylalanine-free amino acid mixture. Tyrosine concentrations were maintained in the range 100-200 mumol/l by restricting natural protein intake to 0.16 g/kg per 24 h in early pregnancy, with increases up to 0.38 g/kg per 24 h in the last trimester. This treatment maintained plasma phenylalanine concentrations in the range 20-40 mumol/l. Maternal weight gain and fetal growth were normal, and the mother remained asymptomatic throughout the pregnancy. A normal infant was born at term with length, weight and head circumference between the 25-50th per centiles.

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Tyrosine availability and brain noradrenaline synthesis in the fetus: control by maternal tyrosine ingestion

Cited by 17 publications

References 45 publications

D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei.

D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic nuclei.

Undernutrition and Overnutrition in the Neonatal Rat: Long-Term Effects on Noradrenergic Pathways in Brain Regions

Maternal tyrosinaemia II: Management and successful outcome

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