scholarly journals Deletion of the Clock Gene Period2 (Per2) in Glial Cells Alters Mood-Related Behavior in Mice

2020 ◽  
Author(s):  
Tomaz Martini ◽  
Jürgen A. Ripperger ◽  
Jimmy Stalin ◽  
Andrej Kores ◽  
Michael Stumpe ◽  
...  

AbstractThe circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, do not only affect circadian activity rhythms, but can also modulate food-anticipatory and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to a depression-resistant phenotype, as manifested in reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 3 (Gat3) mRNA and a reduction of glutamate levels in the nucleus accumbens (NAc). Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomaz Martini ◽  
Jürgen A. Ripperger ◽  
Jimmy Stalin ◽  
Andrej Kores ◽  
Michael Stumpe ◽  
...  

AbstractThe circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, affects not only circadian activity rhythms, but can also modulate feeding and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors, without affecting circadian activity parameters. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 2 (Gat2/Slc6a13) and Dopamine receptor D3 (Drd3) mRNA, and a reduction of glutamate levels in the nucleus accumbens (NAc). Interestingly, neuronal Per2 knock-out also reduces despair, but does not influence anxiety. The change in mood-related behavior is not a result of a defective molecular clock, as glial Bmal1 deletion has no effect on neither despair nor anxiety. Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.


2007 ◽  
Vol 353 (4) ◽  
pp. 1017-1022 ◽  
Author(s):  
Johji Nomura ◽  
Akinori Hisatsune ◽  
Takeshi Miyata ◽  
Yoichiro Isohama

2018 ◽  
Vol 27 (9) ◽  
pp. 1533-1544 ◽  
Author(s):  
Daniel J Flores ◽  
ThuyVy Duong ◽  
Luke O Brandenberger ◽  
Apratim Mitra ◽  
Aditya Shirali ◽  
...  

2015 ◽  
Vol 112 (6) ◽  
pp. 1862-1867 ◽  
Author(s):  
Anton Liaimer ◽  
Eric J. N. Helfrich ◽  
Katrin Hinrichs ◽  
Arthur Guljamow ◽  
Keishi Ishida ◽  
...  

Nostoc punctiformeis a versatile cyanobacterium that can live either independently or in symbiosis with plants from distinct taxa. Chemical cues from plants andN. punctiformewere shown to stimulate or repress, respectively, the differentiation of infectious motile filaments known as hormogonia. We have used a polyketide synthase mutant that accumulates an elevated amount of hormogonia as a tool to understand the effect of secondary metabolites on cellular differentiation ofN. punctiforme. Applying MALDI imaging to illustrate the reprogramming of the secondary metabolome, nostopeptolides were identified as the predominant difference in thepks2−mutant secretome. Subsequent differentiation assays and visualization of cell-type-specific expression of nostopeptolides via a transcriptional reporter strain provided evidence for a multifaceted role of nostopeptolides, either as an autogenic hormogonium-repressing factor or as a chemoattractant, depending on its extracellular concentration. Although nostopeptolide is constitutively expressed in the free-living state, secreted levels dynamically change before, during, and after the hormogonium differentiation phase. The metabolite was found to be strictly down-regulated in symbiosis withGunnera manicataandBlasia pusilla, whereas other metabolites are up-regulated, as demonstrated via MALDI imaging, suggesting plants modulate the fine-balanced cross-talk network of secondary metabolites withinN. punctiforme.


2019 ◽  
Author(s):  
Leila Haery ◽  
Benjamin E. Deverman ◽  
Katherine Matho ◽  
Ali Cetin ◽  
Kenton Woodard ◽  
...  

AbstractCell-type-specific expression of molecular tools and sensors is critical to construct circuit diagrams and to investigate the activity and function of neurons within the nervous system. Strategies for targeted manipulation include combinations of classical genetic tools such as Cre/loxP and Flp/FRT, use of cis-regulatory elements, targeted knock-in transgenic mice, and gene delivery by AAV and other viral vectors. The combination of these complex technologies with the goal of precise neuronal targeting is a challenge in the lab. This report will discuss the theoretical and practical aspects of combining current technologies and establish best practices for achieving targeted manipulation of specific cell types. Novel applications and tools, as well as areas for development, will be envisioned and discussed.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi26-vi26
Author(s):  
Pendelton King ◽  
Alyssa Guo ◽  
Jingwei Wan ◽  
Mingli Liu

Abstract BACKGROUND Non-coding RNAs, including LncRNAs, function in regulating glioblastomas’ numerous oncogenic phenotypes, such as invasiveness and stemness of glioblastoma stem cells. These LncRNAs contain long non-encoding RNA transcripts >200 nucleotides in length, many of which show cell type-specific expression. In this project, we investigated how TRPM7, a promoter for glioma’s proliferation and invasion, regulates LncRNA and contributes to glioma tumorigenesis. METHODS 1) Total RNA, from either with A172 glioma cells or A172 glioma cells with TRPM7 knocked out (A172 KO), were extracted and then parallelly subjected to Human Cancer Pathway Finder, RT2 LncRNA PCR Array. 2) We then analyzed the prognostic role of LncRNAs using a publicly available bioinformatics data set (www.Oncolanc.org). 3) We examined the effects of TRPM7-regulated LncRNA, and its downstream molecules miR301a-3p and FosL1 oncogene, on the proliferation and invasion of glioma cells in A172 and PDX-L12 cells by either inhibition or activation of the above molecules. RESULTS 1) Data analysis from RT2 data resulted in a list of 10 downregulated and 7 upregulated LncRNAs whose transcripts are statistically significant with fold changes greater than 2.0 by TRPM7 knockout. 2) The results showed that TRPM7 functions as a positive regulator of LncRNA, HOTAIR, which is an unfavorable prognostic factor of 7-year overall survival in glioma patients. 3) In addition, we found that LncRNA HOTAIR sponges miR-301a-3p to promote proliferation, invasion, and stemness of glioma through upregulating the oncogene FosL1. 4) Furthermore, we identified that FosL1 is a novel prognostic marker of glioma patients. CONCLUSION Our results demonstrated the role of TRPM7-regulated LncRNA HOTAIR as a miRNA sponge in glioma, which shed new light on LncRNA-directed therapeutics in glioma.


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