The Role of the Y Chromosome in Brain Function

Kopsida, Eleni; Stergiakouli, Evie; Lynn, Phoebe Mei-Ying; Wilkinson, Lawrence S.; Davies, William

doi:10.2174/1876528900902010020

Cited by 63 publications

(47 citation statements)

References 128 publications

(134 reference statements)

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“…Only female mice were utilized in the study to avoid the downstream effects of Y-linked genes on neural sexual differentiation [37]. Total RNA was purified from each tissue, with assessment of RNA quality and quantification of purified RNA performed according to methods described previously [29].…”

Section: Methodsmentioning

confidence: 99%

Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

et al. 2014

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BackgroundThe Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84.ResultsGene expression profiling identified a total of 317 differentially expressed genes (DEGs), selected from various spatiotemporal comparisons, between Ts1Cje and disomic mice. A total of 201 DEGs were identified from the cerebellum, 129 from the hippocampus and 40 from the cerebral cortex. Of these, only 18 DEGs were identified as common to all three brain regions and 15 were located in the triplicated segment. We validated 8 selected DEGs from the cerebral cortex (Brwd1, Donson, Erdr1, Ifnar1, Itgb8, Itsn1, Mrps6 and Tmem50b), 18 DEGs from the cerebellum (Atp5o, Brwd1, Donson, Dopey2, Erdr1, Hmgn1, Ifnar1, Ifnar2, Ifngr2, Itgb8, Itsn1, Mrps6, Paxbp1, Son, Stat1, Tbata, Tmem50b and Wrb) and 11 DEGs from the hippocampus (Atp5o, Brwd1, Cbr1, Donson, Erdr1, Itgb8, Itsn1, Morc3, Son, Tmem50b and Wrb). Functional clustering analysis of the 317 DEGs identified interferon-related signal transduction as the most significantly dysregulated pathway in Ts1Cje postnatal brain development. RT-qPCR and western blotting analysis showed both Ifnar1 and Stat1 were over-expressed in P84 Ts1Cje cerebral cortex and cerebellum as compared to wild type littermates.ConclusionsThese findings suggest over-expression of interferon receptor may lead to over-stimulation of Jak-Stat signaling pathway which may contribute to the neuropathology in Ts1Cje or DS brain. The role of interferon mediated activation or inhibition of signal transduction including Jak-Stat signaling pathway has been well characterized in various biological processes and disease models including DS but information pertaining to the role of this pathway in the development and function of the Ts1Cje or DS brain remains scarce and warrants further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-624) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

et al. 2014

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“…Whilst small in number, X- and Y-linked genes are proportionally abundant in the brain and have been shown to influence neural development and function [276,277]. For instance, genes on the sex chromosome may influence neurological diseases by altering the basic differentiation process of the neurons [278], encoding proteins [279], neurotransmitter biosynthesis [26,280] and synaptic transmission [281].…”

Section: Role Of Sex Hormones and Sex Chromosome Genes In Susceptimentioning

confidence: 99%

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

et al. 2018

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Males and females sometimes significantly differ in their propensity to develop neurological disorders. Females suffer more from mood disorders such as depression and anxiety, whereas males are more susceptible to deficits in the dopamine system including Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD) and autism. Despite this, biological sex is rarely considered when making treatment decisions in neurological disorders. A better understanding of the molecular mechanism(s) underlying sex differences in the healthy and diseased brain will help to devise diagnostic and therapeutic strategies optimal for each sex. Thus, the aim of this review is to discuss the available evidence on sex differences in neuropsychiatric and neurodegenerative disorders regarding prevalence, progression, symptoms and response to therapy. We also discuss the sex-related factors such as gonadal sex hormones and sex chromosome genes and how these might help to explain some of the clinically observed sex differences in these disorders. In particular, we highlight the emerging role of the Y-chromosome gene, SRY, in the male brain and its potential role as a male-specific risk factor for disorders such as PD, autism, and ADHD in many individuals.

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“…Sexual differentiation in the male initially involves the interaction of SRY with SF1 to stimulate (via SOX9) Sertoli cell development in the genital ridges, which subsequently differentiate into testes (Sekido & Lovell-Badge 2008). However, there are other important central and peripheral regions expressing SRY, which contribute to the development of a phenotypically male or female neonate, including heart, liver and kidneys, but particularly the brain and adrenal glands (Kopsida et al 2009). Cells derived from day 10.5 mouse embryos and grown in culture show similar patterns and rates of cell division irrespective of chromosomal sex but differ in their sensitivity to applied insults (e.g.…”

Section: Genetic and Morphological Differences In Developmentmentioning

confidence: 99%

Sex differences in developmental programming models

2013

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The theory of developmental programming suggests that diseases such as the metabolic syndrome may be 'programmed' by exposure to adverse stimuli during early development. The developmental programming literature encompasses the study of a wide range of suboptimal intrauterine environments in a variety of species and correlates these with diverse phenotypic outcomes in the offspring. At a molecular level, a large number of variables have been measured and suggested as the basis of the programmed phenotype. The range of both dependent and independent variables studied often makes the developmental programming literature complex to interpret and the drawing of definitive conclusions difficult. A common, though under-explored, theme of many developmental programming models is a sex difference in offspring outcomes. This holds true across a range of interventions, including dietary, hypoxic, and surgical models. The molecular and phenotypic outcomes of adverse in utero conditions are often more prominent in male than female offspring, although there is little consideration given to the basis for this observation in most studies. We review the evidence that maternal energy investment in male and female conceptuses may not be equal and may be environment dependent. It is suggested that male and female development could be viewed as separate processes from the time of conception, with differences in both timing and outcomes.Reproduction (2013) 145 R1-R13

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The Role of the Y Chromosome in Brain Function

Cited by 63 publications

References 128 publications

Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

Sex differences in developmental programming models

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