Developmental Alcohol Exposure in Drosophila: Effects on Adult Phenotypes and Gene Expression in the Brain

Fetal alcohol exposure can lead to developmental abnormalities, intellectual disability, and behavioral changes, collectively termed fetal alcohol spectrum disorder (FASD). In 2015, the Centers for Disease Control found that 1 in 10 pregnant women report alcohol use and more than 3 million women in the USA are at risk of exposing their developing fetus to alcohol. Drosophila melanogaster is an excellent genetic model to study developmental effects of alcohol exposure because many individuals of the same genotype can be reared rapidly and economically under controlled environmental conditions. Flies exposed to alcohol undergo physiological and behavioral changes that resemble human alcohol-related phenotypes. Here, we show that adult flies that developed on ethanol-supplemented medium have decreased viability, reduced sensitivity to ethanol, and disrupted sleep and activity patterns. To assess the effects of exposure to alcohol during development on brain gene expression, we performed single cell RNA sequencing and resolved cell clusters with differentially expressed genes which represent distinct neuronal and glial populations. Differential gene expression showed extensive sexual dimorphism with little overlap between males and females. Gene expression differences following developmental alcohol exposure were similar to previously reported differential gene expression following cocaine consumption, suggesting that common neural substrates respond to both drugs. Genes associated with glutathione metabolism, lipid transport, glutamate and GABA metabolism, and vision feature in sexually dimorphic global multi-cluster interaction networks. Our results provide a blueprint for translational studies on alcohol-induced effects on gene expression in the brain that may contribute to or result from FASD in human populations.

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Developmental Alcohol Exposure in Drosophila: Effects on Adult Phenotypes and Gene Expression in the Brain

10.1101/2021.04.22.440913 ◽

2021 ◽

Author(s):

Sneha S. Mokashi ◽

Vijay Shankar ◽

Rebecca A. MacPherson ◽

Rachel C. Hannah ◽

Trudy F. C. Mackay ◽

...

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Genetic Model ◽

Alcohol Exposure ◽

Behavioral Changes ◽

Glutathione Metabolism ◽

Human Populations ◽

Fetal Alcohol ◽

Differential Gene ◽

The Brain

Fetal alcohol exposure can lead to developmental abnormalities, intellectual disability, and behavioral changes, collectively termed fetal alcohol spectrum disorder (FASD). In 2015, the Centers for Disease Control found that 1 in 10 pregnant women report alcohol use and more than 3 million women in the USA are at risk of exposing their developing baby to alcohol. Drosophila melanogaster is an excellent genetic model to study developmental effects of alcohol exposure because many individuals of the same genotype can be reared rapidly and economically under controlled environmental conditions. Flies exposed to alcohol undergo physiological and behavioral changes that resemble human alcohol-related phenotypes. Here, we show that adult flies that developed on ethanol-supplemented medium have decreased viability, reduced sensitivity to ethanol, and disrupted sleep and activity patterns. To assess the effects of exposure to alcohol during development on brain gene expression, we performed single cell RNA sequencing and resolved cell clusters with differentially expressed genes which represent distinct neuronal and glial populations. Differential gene expression showed extensive sexual dimorphism with little overlap between males and females. Gene expression differences following developmental alcohol exposure were similar to previously reported differential gene expression following cocaine consumption, suggesting that common neural substrates respond to both drugs. Genes associated with glutathione metabolism, lipid transport, glutamate and GABA metabolism, and vision feature in sexually dimorphic global multi-cluster interaction networks. Our results provide a blueprint for translational studies on alcohol-induced effects on gene expression in the brain that may contribute to or result from FASD in human populations.

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Ethnically biased microsatellites contribute to differential gene expression and glutathione metabolism in Africans and Europeans

PLoS ONE ◽

10.1371/journal.pone.0249148 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249148

Author(s):

Nick Kinney ◽

Lin Kang ◽

Harpal Bains ◽

Elizabeth Lawson ◽

Mesam Husain ◽

...

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Differentially Expressed ◽

Tissue Type ◽

Glutathione Metabolism ◽

Human Populations ◽

Rna Seq ◽

Blood Gene Expression ◽

Relative Contribution ◽

Differential Gene

Approximately three percent of the human genome is occupied by microsatellites: a type of short tandem repeat (STR). Microsatellites have well established effects on (a) the genetic structure of diverse human populations and (b) expression of nearby genes. These lines of inquiry have uncovered 3,984 ethnically biased microsatellite loci (EBML) and 28,375 expression STRs (eSTRs), respectively. We hypothesize that a combination of EBML, eSTRs, and gene expression data (RNA-seq) can be used to show that microsatellites contribute to differential gene expression and phenotype in human populations. In fact, our previous study demonstrated a degree of mutual overlap between EBML and eSTRs but fell short of quantifying effects on gene expression. The present work aims to narrow the gap. First, we identify 313 overlapping EBML/eSTRs and recapitulate their mutual overlap. The 313 EBML/eSTRs are then characterized across ethnicity and tissue type. We use RNA-seq data to pursue validation of 49 regions that affect whole blood gene expression; 32 out of 54 affected genes are differentially expressed in Africans and Europeans. We quantify the relative contribution of these 32 genes to differential expression; fold change tends to be less than other differentially expressed genes. Repeat length correlates with expression for 15 of the 32 genes; two are conspicuously involved in glutathione metabolism. Finally, we repurpose a mathematical model of glutathione metabolism to investigate how a single polymorphic microsatellite affects phenotype. We conclude with a testable prediction that microsatellite polymorphisms affect GPX7 expression and oxidative stress in Africans and Europeans.

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Vascular Genomics of the Human Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200203000-00001 ◽

2002 ◽

Vol 22 (3) ◽

pp. 245-252 ◽

Cited By ~ 36

Author(s):

Eric V. Shusta ◽

Ruben J. Boado ◽

Gary W. Mathern ◽

William M. Pardridge

Keyword(s):

Gene Expression ◽

Human Brain ◽

Differential Gene Expression ◽

Molecular Transport ◽

Brain Diseases ◽

Microvascular Endothelium ◽

Whole Brain ◽

Differential Gene ◽

Brain Microvasculature ◽

The Brain

The microvasculature of the human brain plays an important role in the development and maintenance of the central nervous system and in the pathogenesis of brain diseases, and is the site of differential gene expression within the brain. However, human brain microvascular-specific genes may not be detected in whole-brain gene microarray because the volume of the brain microvascular endothelium is relatively small (0.1%) compared with the whole brain. Therefore, the differential gene expression within the human brain microvasculature was evaluated using suppression subtractive hybridization with RNA isolated from human brain microvessels. Gene identification was restricted to the first 71 clones that were differentially expressed at the brain microvasculature. Twenty of these were genes encoding proteins with known function that were involved in angiogenesis, neurogenesis, molecular transport, and maintenance of endothelial tight junctions or the cytoskeleton. Eighteen genes coding for proteins of an unknown function were identified, including five genes containing satellite DNA sequences. The results provide the initial outline of the genomics of the human brain microvasculature, and have implications for the identification of both targets for brain-specific drug transport and changes in microvascular gene expression in brain diseases.

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Cognitive Stimulation Induces Differential Gene Expression in Octopus vulgaris: The Key Role of Protocadherins

Biology ◽

10.3390/biology9080196 ◽

2020 ◽

Vol 9 (8) ◽

pp. 196

Author(s):

Valeria Maselli ◽

Gianluca Polese ◽

Al-Sayed Al-Soudy ◽

Maria Buglione ◽

Anna Di Cosmo

Keyword(s):

Gene Expression ◽

Differential Gene Expression ◽

Adult Neurogenesis ◽

Control Cell ◽

Enriched Environment ◽

Cognitive Stimulation ◽

Octopus Vulgaris ◽

Brain Areas ◽

Differential Gene ◽

The Brain

Octopuses are unique invertebrates, with sophisticated and flexible behaviors controlled by a high degree of brain plasticity, learning, and memory. Moreover, in Octopus vulgaris, it has been demonstrated that animals housed in an enriched environment show adult neurogenesis in specific brain areas. Firstly, we evaluated the optimal acclimatization period needed for an O. vulgaris before starting a cognitive stimulation experiment. Subsequently, we analyzed differential gene expression in specific brain areas in adult animals kept in tested (enriched environment), wild (naturally enriched environment), and control conditions (unenriched environment). We selected and sequenced three protocadherin genes (PCDHs) involved in the development and maintenance of the nervous system; three Pax genes that control cell specification and tissue differentiation; the Elav gene, an earliest marker for neural cells; and the Zic1 gene, involved in early neural formation in the brain. In this paper, we evaluated gene expression levels in O. vulgaris under different cognitive stimulations. Our data shows that Oct-PCDHs genes are upregulated in the learning and lower motor centers in the brain of both tested and wild animals (higher in the latter). Combining these results with our previous studies on O. vulgaris neurogenesis, we proposed that PCDH genes may be involved in adult neurogenesis processes, and related with their cognitive abilities.

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