using-chronic-social-stress-to-model-postpartum-depression-lactating

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals ...

Manchester Metropolitan University

Alternative splicing serves to increase biological diversity and adaptation. Many genes, including the glucocorticoid receptor (GR), contain multiple 5'-untranslated exons in their promoter regions that can give rise to various mRNA isoforms encoding the same protein. To date, information on the mouse GR promoter remains sparse. Here, we extensively characterize alternative first exons of the mouse GR to reveal homology to the rat and human. We further find that, although most promoters are broadly expressed in various tissues, transcription of individual promoters can be differentially regulated by growth factor- and depolarization-induced signaling. Moreover, in addition to selective promoter usage, the alternative first exon transcripts differentially control RNA stability and translation efficiency, indicative of their role in GR expression. In conclusion, the composite GR promoter enables multilayered adjustments in gene expression through transcriptional and posttranscriptional mechanisms that may serve varying physiological demands.

Differential regulation and function of 5'-untranslated GR-exon 1 transcripts.

&Eacute;pissage alternatif sert &agrave; augmenter la diversit&eacute; biologique et adaptation. Plusieurs g&egrave;nes, y compris le r&eacute;cepteur des glucocortico&iuml;des (GR), contiennent plusieurs exons non traduite de 5&#39; dans leurs r&eacute;gions promotrices qui peuvent donner lieu &agrave; diverses isoformes d&#39;ARNm codant pour la prot&eacute;ine m&ecirc;me. &Agrave; ce jour, les informations sur la souris promoteur GR reste clairsem&eacute;e. Ici, nous caract&eacute;risons intensivement les exons premi&egrave;res alternatives de la souris GR pour r&eacute;v&eacute;ler l&#39;homologie au rat et humaine. Plus loin, nous trouvons que, transcription de divers promoteurs peut &ecirc;tre r&eacute;glement&eacute;e par le facteur de croissance-d&eacute;polarisation induite et signalisation bien que la plupart des promoteurs sont largement exprim&eacute;es dans divers tissus, diff&eacute;remment. En outre, en plus de l&#39;utilisation du promoteur s&eacute;lectif, les transcriptions d&#39;exon premi&egrave;res alternative diff&eacute;rentiellement contr&ocirc;lent l&#39;efficacit&eacute; stabilit&eacute; et traduction RNA, indicative de leur r&ocirc;le dans l&#39;expression de GR. En conclusion, le promoteur GR composite permet des ajustements par multicouches dans l&#39;expression des g&egrave;nes par le biais de transcriptionnelles et post-transcriptionnelle des m&eacute;canismes qui peuvent servir &agrave; diverses exigences physiologiques.

R&eacute;gulation diff&eacute;rentielle et fonction de transcriptions de GR-exon 1 non traduite de 5&#39;.

Splicing alternativo serve per aumentare la diversit&agrave; biologica e adattamento. Molti geni, tra cui i recettori glucocorticoidi (GR), contengono pi&ugrave; esoni 5&#39;-non tradotta nelle loro regioni promotore che possono dare origine a diverse isoforme di mRNA codifica per la proteina stessa. Fino ad oggi, informazioni sul mouse promotore GR rimane scarsa. Qui, abbiamo ampiamente caratterizzano esoni alternativi primi del mouse GR per rivelare omologia di ratto e umani. Troviamo inoltre che, anche se la maggior parte dei promotori sono largamente espressi nei vari tessuti, trascrizione dei singoli promotori differenziale regolabile da fattore di crescita - e depolarizzazione indotta di segnalazione. Inoltre, oltre all&#39;utilizzo del promotore selettiva, le trascrizioni di esone alternativo prime controllano differenzialmente RNA traduzione di stabilit&agrave; e di efficienza, indicativo del loro ruolo nell&#39;espressione GR. In conclusione, il promotore GR composito consente multistrati regolazioni nell&#39;espressione genica attraverso meccanismi trascrizionali e posttranscriptional che possono servire diverse esigenze fisiologiche.

Regolamento differenziale e la funzione delle trascrizioni GR-esone 1 5&#39;-non tradotta.

Maternal mood disorders such as depression and chronic anxiety can negatively affect the lives of both mothers and their adult offspring. An active focus of maternal depression and anxiety research has been the role of chronic social stress in the development of these disorders. Chronic exposure to social stress is common in humans, especially in lactating mothers, and postpartum mood disorders have been correlated with high levels of social conflict and low levels of social support. Recent studies have described an effective and ethologically relevant chronic social stress (CSS) based rodent model for postpartum depression and anxiety. Since CSS attenuates maternal behavior and impairs both dam and offspring growth, it was hypothesized that CSS is an ethologically relevant form of early life stress for the developing female offspring and may have effects on subsequent adult maternal behavior and neuroendocrinology. Dams exposed to early life CSS as infants display substantial increases in pup retrieval and nursing behavior that are specifically associated with attenuated oxytocin, prolactin, and vasopressin gene expression in brain nuclei involved in the control of maternal behavior. Since the growth patterns of both groups were similar despite substantial increases in nursing duration, the early life CSS dams exhibited an attenuated nursing efficiency. It is concluded that early life CSS has long term effects on the neuroendocrinology of maternal care (oxytocin and prolactin) which results in decreased nursing efficiency in the adult dams. The data support the use of early life CSS as an effective model for stress-induced impairments in nursing, such as those associated with postpartum depression and anxiety.

Effects of early life social stress on maternal behavior and neuroendocrinology.

Troubles de l&#39;humeur maternelle tels que la d&eacute;pression et l&#39;anxi&eacute;t&eacute; chronique peuvent affecter n&eacute;gativement la vie des m&egrave;res et leur prog&eacute;niture adulte. Un foyer actif de recherches de d&eacute;pression et d&#39;anxi&eacute;t&eacute; maternelle a &eacute;t&eacute; le r&ocirc;le du stress social chronique dans le d&eacute;veloppement de ces troubles. Une exposition chronique &agrave; des tensions sociales est commune chez les humains, en particulier dans les m&egrave;res qui allaitent, et troubles de l&#39;humeur post-partum ont &eacute;t&eacute; corr&eacute;l&eacute;s avec les niveaux &eacute;lev&eacute;s de conflits sociaux et de faibles niveaux de soutien social. Des &eacute;tudes r&eacute;centes ont d&eacute;crit un mod&egrave;le de rongeur efficace et pertinent &eacute;thologiquement social stress chronique (CSS) bas&eacute; pour l&#39;anxi&eacute;t&eacute; et la d&eacute;pression post-partum. Comme CSS att&eacute;nue le comportement maternel et entrave la croissance de barrage et de prog&eacute;niture, il a &eacute;t&eacute; &eacute;mis l&#39;hypoth&egrave;se que CSS est une forme &eacute;thologiquement pertinente de stress de la vie au d&eacute;but pour la prog&eacute;niture femelle en d&eacute;veloppement et peuvent avoir des effets ult&eacute;rieur comportement maternel adulte et neuroendocrinologie. M&egrave;res expos&eacute;es au d&eacute;but de la vie CSS que les nourrissons d&#39;affichage importante augmente dans la r&eacute;cup&eacute;ration du chiot et le comportement de soins infirmiers qui sont sp&eacute;cifiquement associ&eacute;s &agrave; expression att&eacute;nu&eacute;e vasopressine, prolactine et l&#39;ocytocine g&egrave;ne dans les noyaux du cerveau impliqu&eacute;es dans le contr&ocirc;le du comportement maternel. &Eacute;tant donn&eacute; que les profils de croissance des deux groupes &eacute;taient similaires en d&eacute;pit des augmentations substantielles dans la dur&eacute;e de l&#39;allaitement, les barrages CSS vie pr&eacute;coces expose une efficacit&eacute; des soins infirmiers att&eacute;nu&eacute;. On en conclut que la vie pr&eacute;coce CSS a des effets &agrave; long terme sur la neuroendocrinologie de soins maternels (ocytocine et la prolactine) qui entra&icirc;ne une diminution de soins infirmiers efficacit&eacute; chez les m&egrave;res adultes. Les donn&eacute;es appuient l&#39;utilisation de la vie t&ocirc;t CSS comme un mod&egrave;le efficace pour le stress induit par une d&eacute;ficience en soins infirmiers, comme celles associ&eacute;es &agrave; l&#39;anxi&eacute;t&eacute; et la d&eacute;pression post-partum.

Effets du stress social au d&eacute;but de la vie sur le comportement maternel et neuroendocrinologie.

Umore materno disturbi come la depressione e l&#39;ansia cronica pu&ograve; influenzare negativamente la vita di madri e di loro prole adulta. Un attivo centro di ricerca di depressione e ansia materna &egrave; stato il ruolo dello stress cronico sociale nello sviluppo di questi disturbi. L&#39;esposizione cronica di stress sociale &egrave; comune negli esseri umani, soprattutto nelle madri che allattano, e disturbi dell&#39;umore dopo il parto sono state correlate con elevati livelli di conflitto sociale e bassi livelli di sostegno sociale. Recenti studi hanno descritto un modello di roditore efficace e pertinente etologico sociale stress cronico (CSS) basato per ansia e depressione post-partum. Poich&eacute; CSS attenua il comportamento materno e altera la crescita la diga e la prole, &egrave; stato ipotizzato che CSS &egrave; una forma etologico rilevante di stress di vita precoce per la prole femmina in via di sviluppo e pu&ograve; avere effetti sul successivo comportamento materno adulti e neuroendocrinologia. Dighe esposti ai primi anni di vita CSS come neonati display sostanziale aumenta nel comportamento di cura che sono specificamente associati attenuato l&#39;ossitocina, prolattina e vasopressina espressione genica nei nuclei del cervello coinvolti nel controllo del comportamento materno e il recupero del cucciolo. Poich&eacute; i modelli di crescita di entrambi i gruppi erano simili nonostante sostanziali aumenti nella durata di cura, le prime dighe CSS vita esposta un&#39;efficienza infermieristica attenuato. Si &egrave; concluso che primi anni di vita CSS ha effetti di lungo termine sulla neuroendocrinologia della cura materna (ossitocina e prolattina) che si traduce in infermieristica diminuita efficienza in dighe adulte. I dati supportano l&#39;uso dei primi anni di vita CSS come un modello efficace per stress-induced menomazioni in infermieristica, come quelli associati con l&#39;ansia e la depressione post-partum.

Article	Year
Differential regulation and function of 5'-untranslated GR-exon 1 transcripts. Molecular endocrinology (Baltimore, Md.)\| PubMed ID: 21527501	2011
Effects of early life social stress on maternal behavior and neuroendocrinology. Psychoneuroendocrinology\| PubMed ID: 22770862	2013

Christopher A. Murgatroyd

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