Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system

Wong, Peiyan, Sze, Ying, Gray, Laura Jane, Roei Chang, Cecilia Chin, Cai, Shuwei and Zhang, Xiaodong 2015, Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system, Frontiers in behavioral neuroscience, vol. 9, Article Number : 94, pp. 1-13, doi: 10.3389/fnbeh.2015.00094.

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Title Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system
Author(s) Wong, Peiyan
Sze, Ying
Gray, Laura Jane
Roei Chang, Cecilia Chin
Cai, Shuwei
Zhang, Xiaodong
Journal name Frontiers in behavioral neuroscience
Volume number 9
Season Article Number : 94
Start page 1
End page 13
Total pages 13
Publisher Frontiers Research Foundation
Place of publication Lausanne, Switzerland
Publication date 2015-04-27
ISSN 1662-5153
Summary Dysregulations in the brain serotonergic system and exposure to environmental stressors have been implicated in the development of major depressive disorder. Here, we investigate the interactions between the stress and serotonergic systems by characterizing the behavioral and biochemical effects of chronic stress applied during early-life or adulthood in wild type (WT) mice and mice with deficient tryptophan hydroxylase 2 (TPH2) function. We showed that chronic mild stress applied in adulthood did not affect the behaviors and serotonin levels of WT and TPH2 knock-in (KI) mice. Whereas, maternal separation (MS) stress increased anxiety-and depressive-like behaviors of WT mice, with no detectable behavioral changes in TPH2, KI mice. Biochemically, we found that MS WT mice had reduced brain serotonin levels, which was attributed to increased expression of monoamine oxidase A (MAO A). The increased MAO A expression was detected in MS WT mice at 4 weeks old and adulthood. No change in TPH2 expression was detected. To determine whether a pharmacological stressor, dexamethasone (Dex), will result in similar biochemical results obtained from MS, we used an in vitro system, SH-SY5Y cells, and found that Dex treatment resulted in increased MAO A expression levels. We then treated WT mice with Dex for 5 days, either during postnatal days 7-11 or adulthood. Both groups of Dex treated WT mice had reduced basal corticosterone and glucocorticoid receptors expression levels. However, only Dex treatment during PND7-11 resulted in reduced serotonin levels and increased MAO A expression. Just as with MS WT mice, TPH2 expression in PND7-11, Dex-treated WT mice was unaffected. Taken together, our findings suggest that both environmental and pharmacological stressors affect the expression of MAO A, and not TPH2, when applied during the critical postnatal period. This leads to long-lasting perturbations in the serotonergic system, and results in anxiety-and depressive-like behaviors.
Language eng
DOI 10.3389/fnbeh.2015.00094
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Frontiers Research Foundation
Persistent URL http://hdl.handle.net/10536/DRO/DU:30082056

Document type: Journal Article
Collection: School of Medicine
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