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  • 1
    Publication Date: 2010-07-09
    Description: Cocaine addiction is characterized by a gradual loss of control over drug use, but the molecular mechanisms regulating vulnerability to this process remain unclear. Here we report that microRNA-212 (miR-212) is upregulated in the dorsal striatum of rats with a history of extended access to cocaine. Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on cAMP response element binding protein (CREB) signalling. This action occurs through miR-212-enhanced Raf1 activity, resulting in adenylyl cyclase sensitization and increased expression of the essential CREB co-activator TORC (transducer of regulated CREB; also known as CRTC). Our findings indicate that striatal miR-212 signalling has a key role in determining vulnerability to cocaine addiction, reveal new molecular regulators that control the complex actions of cocaine in brain reward circuitries and provide an entirely new direction for the development of anti-addiction therapeutics based on the modulation of noncoding RNAs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916751/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916751/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hollander, Jonathan A -- Im, Heh-In -- Amelio, Antonio L -- Kocerha, Jannet -- Bali, Purva -- Lu, Qun -- Willoughby, David -- Wahlestedt, Claes -- Conkright, Michael D -- Kenny, Paul J -- F32 CA134121/CA/NCI NIH HHS/ -- F32 DA024932/DA/NIDA NIH HHS/ -- R01 DA025983/DA/NIDA NIH HHS/ -- R01 DA025983-03/DA/NIDA NIH HHS/ -- England -- Nature. 2010 Jul 8;466(7303):197-202. doi: 10.1038/nature09202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20613834" target="_blank"〉PubMed〈/a〉
    Keywords: Adenylyl Cyclases/metabolism ; Animals ; Cocaine/*metabolism/pharmacology ; Cocaine-Related Disorders/drug therapy/enzymology/*genetics/*metabolism ; Cyclic AMP Response Element-Binding Protein/*metabolism ; MAP Kinase Kinase Kinases/metabolism ; Male ; MicroRNAs/biosynthesis/genetics/*metabolism ; Neostriatum/drug effects/*metabolism ; Rats ; Rats, Wistar ; Reward ; *Signal Transduction/drug effects ; Transcription Factors/metabolism ; Up-Regulation/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2007-09-29
    Description: The presence of workers that forgo reproduction and care for their siblings is a defining feature of eusociality and a major challenge for evolutionary theory. It has been proposed that worker behavior evolved from maternal care behavior. We explored this idea by studying gene expression in the primitively eusocial wasp Polistes metricus. Because little genomic information existed for this species, we used 454 sequencing to generate 391,157 brain complementary DNA reads, resulting in robust hits to 3017 genes from the honey bee genome, from which we identified and assayed orthologs of 32 honey bee behaviorally related genes. Wasp brain gene expression in workers was more similar to that in foundresses, which show maternal care, than to that in queens and gynes, which do not. Insulin-related genes were among the differentially regulated genes, suggesting that the evolution of eusociality involved major nutritional and reproductive pathways.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toth, Amy L -- Varala, Kranthi -- Newman, Thomas C -- Miguez, Fernando E -- Hutchison, Stephen K -- Willoughby, David A -- Simons, Jan Fredrik -- Egholm, Michael -- Hunt, James H -- Hudson, Matthew E -- Robinson, Gene E -- New York, N.Y. -- Science. 2007 Oct 19;318(5849):441-4. Epub 2007 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Entomology and Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. amytoth@uiuc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17901299" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bees/genetics ; *Biological Evolution ; Brain/metabolism ; Female ; *Gene Expression ; Gene Expression Regulation ; *Genes, Insect ; Insect Proteins/genetics/physiology ; *Maternal Behavior ; Models, Animal ; Reproduction ; *Social Behavior ; Wasps/*genetics/metabolism/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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