Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons

Powrozek, Teresa A.; Olson, Eric C.

doi:10.1016/j.alcohol.2012.07.003

Cited by 17 publications

(18 citation statements)

References 49 publications

(80 reference statements)

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“…While genes involved in myelination, oxidoreductase activity, and glutamate signaling were each enriched in a single module, other gene ontologies such as Golgi vesicle transport/coated membranes, GTPase activity, and mRNA modification were enriched across multiple modules. It has been known that ethanol exposure results in disorganization of the Golgi apparatus (Renau-Piqueras et al, 1985; Romero et al, 2015), a process that likely involves GTPase activity and COPII-mediated vesicular transport (Petrosyan et al, 2015) and can lead to altered lipid metabolism and neurite development (Powrozek and Olson, 2012); all processes strongly implicated by our study in the biological effects of chronic ethanol.…”

Section: Discussionsupporting

confidence: 52%

Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys

Bogenpohl

Smith

Farris

et al. 2019

Front. Mol. Neurosci.

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Despite recent extensive genomic and genetic studies on behavioral responses to ethanol, relatively few new therapeutic targets for the treatment of alcohol use disorder have been validated. Here, we describe a cross-species genomic approach focused on identifying gene networks associated with chronic ethanol consumption. To identify brain mechanisms underlying a chronic ethanol consumption phenotype highly relevant to human alcohol use disorder, and to elucidate potential future therapeutic targets, we conducted a genomic study in a non-human primate model of chronic open-access ethanol consumption. Microarray analysis of RNA expression in anterior cingulate and subgenual cortices from rhesus macaques was performed across multiple cohorts of animals. Gene networks correlating with ethanol consumption or showing enrichment for ethanol-regulated genes were identified, as were major ethanol-related hub genes within these networks. A subsequent consensus module analysis was used to co-analyze monkey data with expression data from a chronic intermittent ethanol vapor-exposure and consumption model in C57BL/6J mice. Ethanol-related gene networks conserved between primates and rodents were enriched for genes involved in discrete biological functions, including; myelination, synaptic transmission, chromatin modification, Golgi apparatus function, translation, cellular respiration, and RNA processing. The myelin-related network, in particular, showed strong correlations with ethanol consumption behavior and displayed marked network reorganization between control and ethanol-drinking animals. Further bioinformatics analysis revealed that these networks also showed highly significant overlap with other ethanol-regulated gene sets. Altogether, these studies provide robust primate and rodent cross-species validation of gene networks associated with chronic ethanol consumption. Our results also suggest potential novel focal points for future therapeutic interventions in alcohol use disorder.

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Section: Discussionsupporting

confidence: 52%

Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys

Bogenpohl

Smith

Farris

et al. 2019

Front. Mol. Neurosci.

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“…The remaining losses were explained by dysmorphic growth due to explant detachment from the culture filter, or problems associated with histological processing. This success rate of roughly 80% (Figure 5) has rendered the explant system suitable for pharmacological studies 26 , as well as the analysis of recessive mutations 7 that adversely affect early cortical development. …”

Section: Representative Resultsmentioning

confidence: 99%

“…Throughout this period the developing neuron is surrounded by the appropriate ECM and cell types that would confront the corresponding cell in vivo. This system has already proved valuable in deciphering the cellular events that underlie ethanol toxicity 26 , layer 6 formation and preplate splitting 7,25 . …”

mentioning

confidence: 99%

<em>Ex utero</em> Electroporation and Whole Hemisphere Explants: A Simple Experimental Method for Studies of Early Cortical Development

Nichols

O’Dell

Powrozek

et al. 2013

JoVE

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Cortical development involves complex interactions between neurons and non-neuronal elements including precursor cells, blood vessels, meninges and associated extracellular matrix. Because they provide a suitable organotypic environment, cortical slice explants are often used to investigate those interactions that control neuronal differentiation and development. Although beneficial, the slice explant model can suffer from drawbacks including aberrant cellular lamination and migration. Here we report a whole cerebral hemisphere explant system for studies of early cortical development that is easier to prepare than cortical slices and shows consistent organotypic migration and lamination. In this model system, early lamination and migration patterns proceed normally for a period of two days in vitro, including the period of preplate splitting, during which prospective cortical layer six forms. We then developed an ex utero electroporation (EUEP) approach that achieves ~80% success in targeting GFP expression to neurons developing in the dorsal medial cortex.The whole hemisphere explant model makes early cortical development accessible for electroporation, pharmacological intervention and live imaging approaches. This method avoids the survival surgery required of in utero electroporation (IUEP) approaches while improving both transfection and areal targeting consistency. This method will facilitate experimental studies of neuronal proliferation, migration and differentiation. Video LinkThe video component of this article can be found at

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“…This dendritic alteration was accompanied by a morphological compaction of the Golgi apparatus, a key support organelle for the growing dendrite (79), as well as a slower reduction in cytoskeletal F-actin and the microtubule associated protein MAP2 content (67). These disruptions are remarkably similar to, but less severe than, disruptions caused by disruption of the Reelin-signaling pathway (80).…”

Section: Whole Hemisphere Explantsmentioning

confidence: 99%

Analysis of Preplate Splitting and Early Cortical Development Illuminates the Biology of Neurological Disease

Olson

2014

Front. Pediatr.

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The development of the layered cerebral cortex starts with a process called preplate splitting. Preplate splitting involves the establishment of prospective cortical layer 6 (L6) neurons within a plexus of pioneer neurons called the preplate. The forming layer 6 splits the preplate into a superficial layer of pioneer neurons called the marginal zone and a deeper layer of pioneer neurons called the subplate. Disruptions of this early developmental event by toxin exposure or mutation are associated with neurological disease including severe intellectual disability. This review explores recent findings that reveal the dynamism of gene expression and morphological differentiation during this early developmental period. Over 1000 genes show expression increases of ≥2-fold during this period in differentiating mouse L6 neurons. Surprisingly, 88% of previously identified non-syndromic intellectual-disability (NS-ID) genes are expressed at this time and show an average expression increase of 1.6-fold in these differentiating L6 neurons. This changing genetic program must, in part, support the dramatic cellular reorganizations that occur during preplate splitting. While different models have been proposed for the formation of a layer of L6 cortical neurons within the preplate, original histological studies and more recent work exploiting transgenic mice suggest that the process is largely driven by the coordinated polarization and coalescence of L6 neurons rather than by cellular translocation or migration. The observation that genes associated with forms of NS-ID are expressed during very early cortical development raises the possibility of studying the relevant biological events at a time point when the cortex is small, contains relatively few cell types, and few functional circuits. This review then outlines how explant models may prove particularly useful in studying the consequence of toxin and mutation on the etiology of some forms of NS-ID.

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Ethanol-induced disruption of Golgi apparatus morphology, primary neurite number and cellular orientation in developing cortical neurons

Cited by 17 publications

References 49 publications

Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys

Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys

<em>Ex utero</em> Electroporation and Whole Hemisphere Explants: A Simple Experimental Method for Studies of Early Cortical Development

Analysis of Preplate Splitting and Early Cortical Development Illuminates the Biology of Neurological Disease

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