Photoperiodic effects on monoamine signaling and gene expression throughout development in the serotonin and dopamine systems

Abstract Photoperiod or the duration of daylight has been implicated as a risk factor in the development of mood disorders. The dopamine and serotonin systems are impacted by photoperiod and are consistently associated with affective disorders. Hence, we evaluated, at multiple stages of postnatal development, the expression of key dopaminergic (TH) and serotonergic (Tph2, SERT, and Pet-1) genes, and midbrain monoamine content in mice raised under control Equinox (LD 12:12), Short winter-like (LD 8:16), or Long summer-like (LD 16:8) photoperiods. Focusing in early adulthood, we evaluated the midbrain levels of these serotonergic genes, and also assayed these gene levels in the dorsal raphe nucleus (DRN) with RNAScope. Mice that developed under Short photoperiods demonstrated elevated midbrain TH expression levels, specifically during perinatal development compared to mice raised under Long photoperiods, and significantly decreased serotonin and dopamine content throughout the course of development. In adulthood, Long photoperiod mice demonstrated decreased midbrain Tph2 and SERT expression levels and reduced Tph2 levels in the DRN compared Short photoperiod mice. Thus, evaluating gene × environment interactions in the dopaminergic and serotonergic systems during multiple stages of development may lead to novel insights into the underlying mechanisms in the development of affective disorders.

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Photoperiodic Effects on Monoamine Signaling & Gene Expression Throughout Development in the Serotonin & Dopamine Systems

10.1101/2020.06.25.171470 ◽

2020 ◽

Cited By ~ 1

Author(s):

Justin K. Siemann ◽

Piper Williams ◽

Turnee N. Malik ◽

Chad Jackson ◽

Noah H. Green ◽

...

Keyword(s):

Affective Disorders ◽

Early Adulthood ◽

Expression Levels ◽

Dopamine Content ◽

Underlying Mechanisms ◽

Gene X Environment Interactions ◽

Monoamine Signaling ◽

Long Photoperiod ◽

Monoamine Content ◽

Multiple Stages

AbstractPhotoperiod or the duration of daylight has been implicated as a risk factor in the development of mood disorders. The dopamine and serotonin systems are impacted by photoperiod and are consistently associated with affective disorders. Hence, we evaluated, at multiple stages of postnatal development, the expression of key dopaminergic (TH) and serotonergic (Tph2, SERT, and Pet-1) genes, and midbrain monoamine content in mice raised under control Equinox (LD 12:12), Short winter-like (LD 8:16), or Long summerlike (LD 16:8) photoperiods. Focusing in early adulthood, we evaluated the midbrain levels of these serotonergic genes, and also assayed these gene levels in the dorsal raphe nucleus (DRN) with RNAScope. Mice that developed under Short photoperiods demonstrated elevated midbrain TH expression levels, specifically during perinatal development compared to mice raised under Long photoperiods, and significantly decreased serotonin and dopamine content throughout the course of development. In adulthood, Long photoperiod mice demonstrated decreased midbrain Tph2 and SERT expression levels and reduced Tph2 levels in the DRN compared Short photoperiod mice. Thus, evaluating gene x environment interactions in the dopaminergic and serotonergic systems during multiple stages of development may lead to novel insights into the underlying mechanisms in the development of affective disorders.

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Executive Function

The Oxford Handbook of Developmental Psychology, Vol. 1 ◽

10.1093/oxfordhb/9780199958450.013.0025 ◽

2013 ◽

pp. 705-743 ◽

Cited By ~ 7

Author(s):

Stephanie M. Carlson ◽

Philip David Zelazo ◽

Susan Faja

Keyword(s):

Executive Function ◽

Early Adulthood ◽

Preschool Period ◽

Age Related ◽

Gene Environment ◽

Recent Emergence ◽

Brain Structure And Function ◽

Atypical Development ◽

Underlying Mechanisms ◽

And Function

Executive function (EF) refers to the set of neurocognitive skills involved in goal-directed problem solving, including working memory, inhibitory control, and set shifting/flexibility. EF depends importantly upon neural networks involving prefrontal cortex, and continues to improve into early adulthood, although major advances in EF occur during the preschool period. Individual differences in EF are increasingly recognized as a key predictor of long-term cognitive and social developmental outcomes. Research suggests that EF is influenced by both distal and proximal factors in development (e.g., socioeconomic status, culture, language, caregiving, gene–environment interactions, and sleep). Importantly, EF can be trained, with corresponding changes to brain structure and function. In this chapter, we review the structure of EF, including “hot EF” (EF in motivationally significant contexts), age-related changes, atypical development, measurement issues, theories of underlying mechanisms, outcomes associated with EF, influences on EF development, and the recent emergence of training studies.

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Experience sampling research in psychopathology: opening the black box of daily life

Psychological Medicine ◽

10.1017/s0033291708004947 ◽

2009 ◽

Vol 39 (9) ◽

pp. 1533-1547 ◽

Cited By ~ 389

Author(s):

I. Myin-Germeys ◽

M. Oorschot ◽

D. Collip ◽

J. Lataster ◽

P. Delespaul ◽

...

Keyword(s):

Daily Life ◽

Experience Sampling ◽

Added Value ◽

Cross Sectional ◽

Gene Environment ◽

Psychological Models ◽

Research Findings ◽

Underlying Mechanisms ◽

New Research ◽

Momentary Assessment

A growing body of research suggests that momentary assessment technologies that sample experiences in the context of daily life constitute a useful and productive approach in the study of behavioural phenotypes and a powerful addition to mainstream cross-sectional research paradigms. Momentary assessment strategies for psychopathology are described, together with a comprehensive review of research findings illustrating the added value of daily life research for the study of (1) phenomenology, (2) aetiology, (3) psychological models, (4) biological mechanisms, (5) treatment and (6) gene–environment interactions in psychopathology. Overall, this review shows that variability over time and dynamic patterns of reactivity to the environment are essential features of psychopathological experiences that need to be captured for a better understanding of their phenomenology and underlying mechanisms. The Experience Sampling Method (ESM) allows us to capture the film rather than a snapshot of daily life reality of patients, fuelling new research into the gene–environment–experience interplay underlying psychopathology and its treatment.

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Basic mechanisms of, and treatment targets for, depressive disorders

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780198713005.003.0074 ◽

2020 ◽

pp. 779-788

Author(s):

Marcela Pereira ◽

Roberto Andreatini ◽

Per Svenningsson

Keyword(s):

Major Depressive Disorder ◽

Immune System ◽

Depressive Disorder ◽

Affective Disorders ◽

Sleep Disturbances ◽

Depressive Disorders ◽

Signs And Symptoms ◽

Molecular Pathways ◽

Therapy Targets ◽

Gene Environment

The diagnosis of major depressive disorder (MDD) relies on the presence of a certain number of signs and symptoms, including feelings of guilt, hopelessness, dysphoria, cognitive dysfunction, persistent sleep, and appetite abnormalities. These signs and symptoms overlap with other conditions such as anxiety, bipolar, and seasonal affective disorders. This chapter provides an overview of the basic neurobiological mechanisms underlying MDD and its treatment. There are several alterations in the molecular pathways and neuronal networks associated with MDD. The chapter focuses here on: gene × environment interactions, dysfunctional brain circuitries, neurotransmitter alterations, maladaptation in neurotrophins and neuroplasticity, hypothalamus–pituitary–adrenal (HPA) axis dysfunction, abnormal immune system responses, circadian arrhythmicity, and sleep disturbances. The chapter briefly describes the mechanisms of actions for approved antidepressant therapies and also discusses recent insights into the pathophysiology of MDD and future possible therapy targets.

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Everyday creativity and bipolar and unipolar affective disorder: preliminary study of personal and family history

European Psychiatry ◽

10.1017/s092493380000328x ◽

1992 ◽

Vol 7 (2) ◽

pp. 49-52 ◽

Cited By ~ 5

Author(s):

R Richards ◽

DK Kinney ◽

H Daniels ◽

K Linkins

Keyword(s):

Bipolar Disorder ◽

Family History ◽

Affective Disorder ◽

Affective Disorders ◽

Bipolar Disorders ◽

Data Support ◽

History Of ◽

Preliminary Study ◽

Everyday Creativity ◽

Underlying Mechanisms

SummaryPreliminary new data support the enhancement of ‘everyday’ creativity among those persons with bipolar disorders who manifest milder rather than more severe mood elevations, and among certain individuals who are likely to carry bipolar liability but themselves show no clinical mood elevations – in this case, unipolar depressives with a family history of bipolar disorder, when compared with depressives lacking this history. Creativity was assessed using the lifetime creativity scales (Richards el al, 1988). Underlying mechanisms may be multifactorial and complex. Results suggest that both personal and family history should be considered when making predictions concerning creativity and affective disorders.

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Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

Cellular Physiology and Biochemistry ◽

10.1159/000487296 ◽

2018 ◽

Vol 45 (3) ◽

pp. 1013-1022 ◽

Cited By ~ 6

Author(s):

Ting Zhong ◽

Jiaxiang Chen ◽

Yan Ling ◽

Bei Yang ◽

Xingxing Xie ◽

...

Keyword(s):

Pregnant Women ◽

Normal Pregnancy ◽

Neuropathy Target Esterase ◽

Trophoblast Invasion ◽

Migration And Invasion ◽

Down Regulation ◽

Human Trophoblast ◽

Expression Levels ◽

Transfection Method ◽

Underlying Mechanisms

Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase) is proven to deacylate phosphatidylcholine (PC) to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE)-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

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Molecular genetic findings in mood disorders

Acta Neuropsychiatrica ◽

10.1017/s092427080003619x ◽

1999 ◽

Vol 11 (2) ◽

pp. 67-70

Author(s):

D. Souery ◽

J. Mendlewicz

Keyword(s):

Affective Disorders ◽

Bipolar Affective Disorder ◽

Molecular Genetic ◽

Family Studies ◽

Allelic Association ◽

Psychiatric Diseases ◽

New Developments ◽

Genetic Transmission ◽

Gene Environment ◽

The Us

Traditional methods used to asses genetic effects, such as twins, adoption and family studies, have demonstrated the role genetic vulnerability factors in the etiology of major psychiatric diseases such as affective disorders and schizophrenia. It remains however impossible, using these methods, to specify the genetic variables involved and the exact mode of transmission of these diseases. New genetic approaches in psychiatry include the use of DNA markers in sophisticated strategies to examine families and populations. Genetic linkage (in families) and allelic association (in unrelated subjects) are the most frequent techniques applied searching for genes in psychiatric diseases. Advances in these methods have permitted their application to complex diseases in which the mode of genetic transmission is unknown. Affective disorders and, in particular, bipolar affective disorder (BPAD) have been examined in many molecular genetic studies which have covered a large part of the genome, specific hypotheses such as mutations have also, been studied. Most recent studies indicate that several chromosomal regions may be involved in the aetiology of affective disorders. Large multi-centre and multi-disciplinary projects are currently underway in Europe and in the US and hopefully will improve our understanding of the genetic factors involved in affective disorders. In parallel to these new developments in molecular genetics, the classical genetic epidemiology, represented by twin, adoption and family studies, have been improved, providing validated models to test the gene-environment interactions.

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Laxative Effects of Yangyin Tongmi Capsule on a Model of Diphenoxylate-Induced Constipation in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1471824 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Shan Liu ◽

Dayun Sui ◽

Wenwen Fu ◽

Xiaofeng Yu ◽

Yuangeng Li ◽

...

Keyword(s):

Low Dose ◽

High Dose ◽

Water Control ◽

Intestinal Hormones ◽

Expression Levels ◽

Laxative Effects ◽

Bowel Movements ◽

Difficult Defecation ◽

Underlying Mechanisms ◽

Related Proteins

Constipation is characterized by reduced number of bowel movements, dry stools, and difficult defecation. Yangyin Tongmi capsule (YTC), a traditional Chinese formula, is used in the treatment of constipation, while the underlying mechanisms remain unknown. Herein, this work attempted to prove the effects of YTC on constipation treatment and its possible mechanisms. KM mice were randomly divided into four groups (n = 10/group) and treated with double distilled water (Control), diphenoxylate (Model: 10 mg/kg), or diphenoxylate plus low-dose YTC (L-YTC: 0.6 g/kg) or high-dose YTC (H-YTC: 1.2 g/kg). The data indicated that YTC can significantly shorten the discharge time of the first black stool, improve intestinal propulsion rate, and increase the water content and quantity of feces in mice. ELISA suggested that YTC regulate the content of intestinal hormones and neurotransmitters, such as motilin (MTL), gastrin (GT), somatostatin (SST), substance P (SP), acetylcholine (Ach), and nitric oxide (NO). The expression levels of aquaporin 3 (AQP3) and aquaporin 8 (AQP8) in the colon were examined by immunohistochemistry. In the meantime, the expression levels of P2X2, C-kit, and stem cell factor (SCF) in the colon were examined by western blot analysis. The results of this study suggest that YTC has mitigative effects on diphenoxylate-induced constipation by regulating the content of intestinal hormones and neurotransmitters and regulating the expression of related proteins in the colon.

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Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma

Archives of Medical Science ◽

10.5114/aoms.2020.100675 ◽

2021 ◽

Vol 17 (1) ◽

pp. 142-151

Author(s):

Jingqi Liu ◽

Ligang Chen ◽

Jinshui Pan ◽

Meiya Chen ◽

Jingping Zhou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Normal Liver ◽

Comprehensive Analysis ◽

Differentially Expressed ◽

Expression Levels ◽

Go Analysis ◽

The Public ◽

Kaplan Meier ◽

Tcga Dataset ◽

Underlying Mechanisms

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.

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Identification of Therapeutic Targets and Prognostic Biomarkers Among Integrin Subunits in the Skin Cutaneous Melanoma Microenvironment

Frontiers in Oncology ◽

10.3389/fonc.2021.751875 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yeltai Nurzat ◽

Weijie Su ◽

Peiru Min ◽

Ke Li ◽

Heng Xu ◽

...

Keyword(s):

T Cells ◽

Cutaneous Melanoma ◽

Regulatory Networks ◽

Disease Free Survival ◽

Enrichment Analysis ◽

Expression Levels ◽

Protein Protein Interaction ◽

Ppi Networks ◽

Go Enrichment ◽

Underlying Mechanisms

The roles of different integrin alpha/beta (ITGA/ITGB) subunits in skin cutaneous melanoma (SKCM) and their underlying mechanisms of action remain unclear. Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, and Webgestalt analysis tools were used. The expression levels of ITGA3, ITGA4, ITGA6, ITGA10, ITGB1, ITGB2, ITGB3, ITGB4, and ITGB7 were significantly increased in SKCM tissues. The expression levels of ITGA1, ITGA4, ITGA5, ITGA8, ITGA9, ITGA10, ITGB1, ITGB2, ITGB3, ITGB5, ITGB6 and ITGB7 were closely associated with SKCM metastasis. The expression levels of ITGA1, ITGA4, ITGB1, ITGB2, ITGB6, and ITGB7 were closely associated with the pathological stage of SKCM. The expression levels of ITGA6 and ITGB7 were closely associated with disease-free survival time in SKCM, and the expression levels of ITGA6, ITGA10, ITGB2, ITGB3, ITGB6, ITGB7, and ITGB8 were markedly associated with overall survival in SKCM. We also found significant correlations between the expression of integrin subunits and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells). Finally, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and protein-protein interaction (PPI) networks were constructed. We have identified abnormally-expressed genes and gene regulatory networks associated with SKCM, improving understanding of the underlying pathogenesis of SKCM.

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