Transport and Metabolism of Serotonin in the Human Placenta from Normal and Severely Pre-Eclamptic Pregnancies

Carrasco, Gonzalo; Cruz, Maria Antonieta; Gallardo, Victoria; Miguel, Patricia; Dominguez, Alejandra; González, Claudio

doi:10.1159/000010237

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…However, no differences between genotypes at earlier time points (at birth and at pnd10), or even downregulation in Bdnf expression levels in TPH2 −/− in comparison to TPH2 +/+ pnd10 male rats were observed, suggesting that peripheral sources may compensate for the lack of central 5-HT synthesis during the early postnatal periods of life. Indeed, the blood brain barrier is not fully functional before pnd12 (Ribatti et al, 2006 ) and 5-HT from the placenta at embryonic stages (Cool et al, 1990 ; Carrasco et al, 2000 ) and from the peripheral blood after birth may easily enter the brain. Accordingly, Vitalis et al ( 2007 ) demonstrated that the embryonic transient 5-HT depletion did not modify cortical BDNF levels until PND21 in pups.…”

Section: Discussionmentioning

confidence: 99%

“…Since in adulthood it cannot pass the blood-brain barrier, these two enzymes define two 5-HT systems with independent regulation and different function. Although in the adult brain 5-HT is produced only by serotonergic neurons in raphe nuclei, during development there are other sources of this monoamine, including maternal 5-HT, that is actively transported through the placental brush border cells via the serotonin transporter (SERT; Cool et al, 1990 ; Carrasco et al, 2000 ; Kliman et al, 2018 ). Moreover, until postnatal day (pnd) 12, the blood-brain barrier is immature (Ribatti et al, 2006 ) and 5-HT, produced by TPH1 starting at embryonic day 14 in rodents (Côté et al, 2007 ) can reach the brain.…”

Section: Introductionmentioning

confidence: 99%

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TPH2 Deficiency Influences Neuroplastic Mechanisms and Alters the Response to an Acute Stress in a Sex Specific Manner

Brivio

Sbrini

Peeva

et al. 2018

Front. Mol. Neurosci.

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Dysregulations of the central serotoninergic system have been implicated in several psychopathologies, characterized by different susceptibility between males and females. We took advantage of tryptophan hydroxylase 2 (TPH2) deficient rats, lacking serotonin specifically in the brain, to investigate whether a vulnerable genotype can be associated with alterations of neuronal plasticity from the early stage of maturation of the brain until adulthood. We found a significant increase, in both gene and protein expression, of the neurotrophin brain-derived neurotrophic factor (BDNF), in the prefrontal cortex (PFC) of adult TPH2-deficient (TPH2−/−) male and female rats in comparison to wild type (TPH2+/+) counterparts. Interestingly, a development-specific pattern was observed during early postnatal life: whereas the increase in Bdnf expression, mainly driven by the modulation of Bdnf isoform IV was clearly visible after weaning at postnatal day (pnd) 30 in both sexes of TPH2−/− in comparison to TPH2+/+ rats, at early stages (pnd1 and pnd10) Bdnf expression levels did not differ between the genotypes, or even were downregulated in male TPH2−/− animals at pnd10. Moreover, to establish if hyposerotonergia may influence the response to a challenging situation, we exposed adult rats to an acute stress. Although the pattern of corticosterone release was similar between the genotypes, neuronal activation in response to stress, quantified by the expression of the immediate early genes activity regulated cytoskeleton associated protein (Arc) and Fos Proto-Oncogene (cFos), was blunted in both sexes of animals lacking brain serotonin. Interestingly, although upregulation of Bdnf mRNA levels after stress was observed in both genotypes, it was less pronounced in TPH2−/− in comparison to TPH2+/+ rats. In summary, our results demonstrated that serotonin deficiency affects neuroplastic mechanisms following a specific temporal pattern and influences the response to an acute stress.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TPH2 Deficiency Influences Neuroplastic Mechanisms and Alters the Response to an Acute Stress in a Sex Specific Manner

Brivio

Sbrini

Peeva

et al. 2018

Front. Mol. Neurosci.

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“…In contrast, there are multiple sources of 5-HT in the developing brain. The first and most important source is the mother: maternal 5-HT is actively transported through the placental brush border cells via SERT (Cool et al, 1990;Carrasco et al, 2000). 5-HT immunostaining is present in the placenta and the ectoplacental cone (Yavarone et al, 1993).…”

Section: -Ht Sources During Developmentmentioning

confidence: 99%

Genetic Models of Serotonin (5‐HT) Depletion: What do They Tell Us About the Developmental Role of 5‐HT?

Trowbridge¹,

Narboux-Nême²,

Gaspar³

2010

The Anatomical Record

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A large number of hyposerotonergic genetic models have been generated over the past few years. Serotonin (5-HT) depletion has been obtained via targeting of genes involved in 5-HT synthesis (Tph1 and Tph2), specification and determination of the 5-HT phenotype during development (GATA3, Pet1, and Lmx1b), and 5-HT storage or clearance (Vmat2 and SERT). Here we review these various models from a developmental perspective, beginning with a description of the sources of 5-HT during development. We then summarize the neurological and behavioral alterations that have been observed in the genetic hyposerotonergic models. Although these models appear to have normal brain development and do not exhibit any gross morphological defects, problems in somatic growth and physiological functions have been observed. Abnormal adult behavior is also seen, although whether it results from depletion of 5-HT during development or functional 5-HT deficiencies in adult life remains unclear. Evidence from these hyposerotonergic models suggests that the developing brain may not need 5-HT for the establishment of general organization and structure. However, central 5-HT appears to be necessary for postnatal body growth, maturation of respiratory and vegetative control, and possibly for the development of normal adult behavior. Anat Rec, 294:1615Rec, 294: -1623Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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“…1). Once inside the syncytiotrophoblast, serotonin is metabolized by monoamine oxidase, an enzyme present abundantly in the placenta (Carrasco et al, 2000; Sivasubramaniam et al, 2002). Thus, the syncytiotrophoblast functions like a sink for serotonin.…”

Section: Effects Of Cocaine and Amphetamines On Pregnant Women – Presmentioning

confidence: 99%

Drugs of abuse and human placenta

Ganapathy

2011

Life Sciences

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Drugs of abuse such as cocaine and amphetamines, when used by pregnant women, exert deleterious effects on the fetus. These drugs produce their effects through inhibition of the serotonin transporter, norepinephrine transporter, and dopamine transporter. The inhibition can occur in the pregnant mother as well as in the fetus. These events contribute to the detrimental effects of these drugs on the fetus. However, the role of placenta, which serves as the link between the pregnant mother and the fetus, in the process remains understudied. It has been assumed that placenta did not play any direct role in the process except that it allowed the passage of these drugs from maternal circulation into fetal circulation. This was before the discovery that placenta expresses two of the three monoamine transporters. The serotonin transporter and the norepinephrine transporter are expressed on the maternal-facing side of the syncytiotrophoblast, thus exposed to the inhibitory actions of cocaine and amphetamines if present in maternal blood. Inhibition of these transporters in placenta could lead to elevation of serotonin and norepinephrine in the intervillous space that may cause uterine contraction and vasoconstriction, resulting in premature delivery, decreased placental blood flow, and intrauterine growth retardation. Thus, the placenta is actually a direct target for these abusable drugs. Since the placental serotonin transporter and norepinephrine transporter are also inhibited by many antidepressants, therapeutic use of these drugs in pregnant women may have similar detrimental effects on placental function and fetal growth and development.

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Transport and Metabolism of Serotonin in the Human Placenta from Normal and Severely Pre-Eclamptic Pregnancies

Cited by 14 publications

References 25 publications

TPH2 Deficiency Influences Neuroplastic Mechanisms and Alters the Response to an Acute Stress in a Sex Specific Manner

TPH2 Deficiency Influences Neuroplastic Mechanisms and Alters the Response to an Acute Stress in a Sex Specific Manner

Genetic Models of Serotonin (5‐HT) Depletion: What do They Tell Us About the Developmental Role of 5‐HT?

Drugs of abuse and human placenta

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