scholarly journals Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure

2013 ◽  
Vol 5 (1) ◽  
pp. 6 ◽  
Author(s):  
Morgan L Kleiber ◽  
Katarzyna Mantha ◽  
Randa L Stringer ◽  
Shiva M Singh
2010 ◽  
Vol 47 (6) ◽  
pp. 1317-1324 ◽  
Author(s):  
Sven Klaschik ◽  
Debra Tross ◽  
Hidekazu Shirota ◽  
Dennis M. Klinman

Author(s):  
Deena M. Walker ◽  
Xianxiao Zhou ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Ashley M. Cunningham ◽  
...  

ABSTRACTAdolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid-binding protein, as a key driver of these transcriptional profiles. Manipulation of Crym specifically within adult meA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence.


2021 ◽  
Author(s):  
Michael Sieweke ◽  
Sethuraman Subramanian ◽  
Clara Busch ◽  
Kaaweh Molawi ◽  
Laufey Geirsdottir ◽  
...  

Abstract Alveolar macrophages (AM) are tissue resident macrophages of the lung that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that long-term ex vivo expanded mouse AM (exAM) maintain core AM gene expression but show culture adaptations related to adhesion, metabolism and proliferation. Strikingly, even after several months in culture exAM reacquired full transcriptional and epigenetic identity upon transplantation into the lung and could self-maintain in the natural niche long-term. Changes in open chromatin regions (OCR) observed in culture were fully reversible in transplanted exAM (texAM) and resulted in a gene expression profile indistinguishable from resident AM. Our results demonstrate that long-term proliferation of AM in culture does not compromise cellular identity in vivo. The demonstrated robustness of exAM identity provides new opportunities for mechanistic analysis and highlights the therapeutic potential of ex vivo expanded macrophages.


Synapse ◽  
2009 ◽  
Vol 63 (5) ◽  
pp. 403-412 ◽  
Author(s):  
Annabelle M. Belcher ◽  
Steven J. O'dell ◽  
John F. Marshall

2021 ◽  
Vol 11 (9) ◽  
pp. 1149
Author(s):  
Brent R. Kisby ◽  
Sean P. Farris ◽  
Michelle M. McManus ◽  
Florence P. Varodayan ◽  
Marisa Roberto ◽  
...  

Alcohol dependence is associated with adverse consequences of alcohol (ethanol) use and is evident in most severe cases of alcohol use disorder (AUD). The central nucleus of the amygdala (CeA) plays a critical role in the development of alcohol dependence and escalation of alcohol consumption in dependent subjects. Molecular mechanisms underlying the CeA-driven behavioral changes are not well understood. Here, we examined the effects of alcohol on global gene expression in the CeA using a chronic intermittent ethanol (CIE) vapor model in rats and RNA sequencing (RNA-Seq). The CIE procedure resulted in robust changes in CeA gene expression during intoxication, as the number of differentially expressed genes (DEGs) was significantly greater than those expected by chance. Over-representation analysis of cell types, functional groups and molecular pathways revealed biological categories potentially important for the development of alcohol dependence in our model. Genes specific for astrocytes, myelinating oligodendrocytes, and endothelial cells were over-represented in the DEG category, suggesting that these cell types were particularly affected by the CIE procedure. The majority of the over-represented functional groups and molecular pathways were directly related to the functions of glial and endothelial cells, including extracellular matrix (ECM) organization, myelination, and the regulation of innate immune response. A coordinated regulation of several ECM metalloproteinases (e.g., Mmp2; Mmp14), their substrates (e.g., multiple collagen genes and myelin basic protein; Mbp), and a metalloproteinase inhibitor, Reck, suggests a specific mechanism for ECM re-organization in response to chronic alcohol, which may modulate neuronal activity and result in behavioral changes, such as an escalation of alcohol drinking. Our results highlight the importance of glial and endothelial cells in the effects of chronic alcohol exposure on the CeA, and demonstrate further insight into the molecular mechanisms of alcohol dependence in rats. These molecular targets may be used in future studies to develop therapeutics to treat AUD.


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