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      Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat

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          Abstract

          Background

          Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses.

          Results

          We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group.

          Conclusions

          Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.

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          Most cited references46

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            Molecular, pharmacological and functional diversity of 5-HT receptors.

            Serotonin (5-hydroxytryptamine, 5-HT) is probably unique among the monoamines in that its effects are subserved by as many as 13 distinct heptahelical, G-protein-coupled receptors (GPCRs) and one (presumably a family of) ligand-gated ion channel(s). These receptors are divided into seven distinct classes (5-HT(1) to 5-HT(7)) largely on the basis of their structural and operational characteristics. Whilst this degree of physical diversity clearly underscores the physiological importance of serotonin, evidence for an even greater degree of operational diversity continues to emerge. The challenge for modern 5-HT research has therefore been to define more precisely the properties of the systems that make this incredible diversity possible. Much progress in this regard has been made during the last decade with the realisation that serotonin is possibly the least conservative monoamine transmitter and the cloning of its many receptors. Coupled with the actions of an extremely avid and efficient reuptake system, this array of receptor subtypes provides almost limitless signalling capabilities to the extent that one might even question the need for other transmitter systems. However, the complexity of the system appears endless, since posttranslational modifications, such as alternate splicing and RNA editing, increase the number of proteins, oligomerisation and heteromerisation increase the number of complexes, and multiple G-protein suggest receptor trafficking, allowing phenotypic switching and crosstalk within and possibly between receptor families. Whether all these possibilities are used in vivo under physiological or pathological conditions remains to be firmly established, but in essence, such variety will keep the 5-HT community busy for quite some time. Those who may have predicted that molecular biology would largely simplify the life of pharmacologists have missed the point for 5-HT research in particular and, most probably, for many other transmitters. This chapter is an attempt to summarise very briefly 5-HT receptor diversity. The reward for unravelling this complex array of serotonin receptor--effector systems may be substantial, the ultimate prize being the development of important new drugs in a range of disease areas.
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              Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice.

              Reduced serotonin transporter (5-HTT) expression is associated with abnormal affective and anxiety-like symptoms in humans and rodents, but the mechanism of this effect is unknown. Transient inhibition of 5-HTT during early development with fluoxetine, a commonly used serotonin selective reuptake inhibitor, produced abnormal emotional behaviors in adult mice. This effect mimicked the behavioral phenotype of mice genetically deficient in 5-HTT expression. These findings indicate a critical role of serotonin in the maturation of brain systems that modulate emotional function in the adult and suggest a developmental mechanism to explain how low-expressing 5-HTT promoter alleles increase vulnerability to psychiatric disorders.
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                Author and article information

                Journal
                BMC Neurosci
                BMC Neurosci
                BMC Neuroscience
                BioMed Central
                1471-2202
                2012
                28 February 2012
                : 13
                : 22
                Affiliations
                [1 ]Department of Pediatrics, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou 515041, Guangdong, China
                [2 ]Department of Neurosurgery, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou 515041, Guangdong, China
                [3 ]Mental Health Center of Shantou University, Tai Shan Rd, Shantou 515041, Guangdong, China
                [4 ]Maternal and Child Health Hospital of Guangdong Province, West Guangyuan Rd, GuangZhou 510010, Guangdong, China
                Article
                1471-2202-13-22
                10.1186/1471-2202-13-22
                3311061
                22373128
                650ff43d-b7cd-48d1-bb56-d6a4d21e2849
                Copyright ©2012 Huang et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 September 2011
                : 28 February 2012
                Categories
                Research Article

                Neurosciences
                corticosterone,serotonin,hpa axis,stress,serotonin transporter
                Neurosciences
                corticosterone, serotonin, hpa axis, stress, serotonin transporter

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