{"title":"Current Strategies of Therapy in Alzheimer`s Disease","authors":"A. Martocchia, P. Falaschi","doi":"10.2174/1876523800801010019","DOIUrl":"https://doi.org/10.2174/1876523800801010019","url":null,"abstract":"","PeriodicalId":88752,"journal":{"name":"The open neuropsychopharmacology journal","volume":"113 1","pages":"19-23"},"PeriodicalIF":0.0,"publicationDate":"2008-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68144278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shin-Ju E. Chang, Samantha Chang-Lin, Donald C. Chang, Chengyi Chang, Shi-Lung Lin, S. Ying
{"title":"Repeat-Associated MicroRNAs Trigger Fragile X Mental Retardation- Like Syndrome in Zebrafish","authors":"Shin-Ju E. Chang, Samantha Chang-Lin, Donald C. Chang, Chengyi Chang, Shi-Lung Lin, S. Ying","doi":"10.2174/1876523800801010006","DOIUrl":"https://doi.org/10.2174/1876523800801010006","url":null,"abstract":"A new class of repeat-associated microRNA (ramRNA) is identified to hinder normal brain development in ze- brafish. Previous studies have shown that small hairpin RNAs derived from the 5'-untranslational CGG/CCG trinucleotide repeat (r(CGG)) expansion of fragile X mental retardation gene 1, FMR1, may cause neuronal toxicity in fragile X mental retardation syndrome (FXS). However, their roles in FXS remain unclear. We report here that over-expression of a novel ramRNA species isolated from the fish FMR1 r(CGG) region triggers FXS-like neurodegeneration in a transgenic zebraf- ish model. Hyper-methylation of the FMR1 5'-r(CGG) region associated with ramRNA over-expression is central to this FXS-like etiology. Such an epigenetic modification results in the transcriptional inactivation of the FMR1 gene and defi- ciency of its protein FMRP. FMRP deficiency further causes neurite deformity and synaptic dysfunction in the hippocam- pal neurons essential for cognition and memory. These findings provide significant insights into the role of ramRNAs in the embryonic brain development.","PeriodicalId":88752,"journal":{"name":"The open neuropsychopharmacology journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2008-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68144269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tolga Uz, Yogesh Dwivedi, Ghanshyam N Pandey, Rosalinda C Roberts, Robert R Conley, Radmila Manev, Hari Manev
{"title":"5-Lipoxygenase in the Prefrontal Cortex of Suicide Victims.","authors":"Tolga Uz, Yogesh Dwivedi, Ghanshyam N Pandey, Rosalinda C Roberts, Robert R Conley, Radmila Manev, Hari Manev","doi":"10.2174/1876523800801010001","DOIUrl":"https://doi.org/10.2174/1876523800801010001","url":null,"abstract":"<p><p>5-lipoxygenase (5-LOX), an enzyme involved in leukotriene synthesis, is expressed in the brain and has been associated with Alzheimer's disease and depression. Recently, it has been suspected that leukotriene receptor antagonists might be associated with suicide. In this work, we investigated the 5-LOX protein in the brain samples from depressed suicide victims and matching controls. We used Western immunoblotting with an antibody against Ser(523)-phosphorylated 5-LOX (p5-LOX) to evaluate protein kinase A-mediated 5-LOX phosphorylation, and in addition, an antibody against the total 5-LOX protein. In the total homogenate of the prefrontal cortex samples, 5-LOX content did not differ in the control and suicide groups but p5-LOX was significantly elevated in the suicide samples. The 5-LOX protein content was reduced in the membrane fraction and increased in the cytosol fraction of suicide victims. We propose that further studies of brain 5-LOX are needed to elucidate the functional implications of the protein alterations observed in our present study, and to further explore a putative role of 5-LOX in depression and suicide.</p>","PeriodicalId":88752,"journal":{"name":"The open neuropsychopharmacology journal","volume":"1 ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772083/pdf/nihms-71383.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28489027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonah J Scott-McKean, Galen R Wenger, Laurence H Tecott, Alberto C S Costa
{"title":"5-HT(1A) Receptor Null Mutant Mice Responding Under a Differential-Reinforcement-of-Low-Rate 72-Second Schedule of Reinforcement.","authors":"Jonah J Scott-McKean, Galen R Wenger, Laurence H Tecott, Alberto C S Costa","doi":"10.2174/1876523800801010024","DOIUrl":"https://doi.org/10.2174/1876523800801010024","url":null,"abstract":"<p><p>Over the last two decades, our ever-increasing ability to manipulate the mouse genome has resulted in a variety of genetically defined mouse models of depression and other psychiatric and neurological disorders. However, it is still the case that some relevant rodent models for depression and antidepressant action have been validated experimentally in rats only and not in mice. An important example of such models is the operant model of antidepressant action known as differential-reinforcement-of-low-rates 72-second (DRL 72-s). A specific set of drug-induced changes on the performance of rats responding under a DRL 72-s schedule of reinforcement has been shown to be a highly reliable predictor of antidepressant activity in human depressive disorders. The aim of this study is to validate the use of the DRL 72-s schedule in mice by both genetic and pharmacological means. We have analyzed the actions of the specific serotonin reuptake inhibitor (SSRI) fluoxetine and the tricyclic agent desipramine (DMI) on wild-type and 5-hydroxytryptamine 1A receptor-null mutant (5-HT(1A)R KO) mice. In agreement with the literature on rats, we found that fluoxetine produced an acute antidepressant-like effect in 5-HT(1A)R KO mice but not in wild-type (Wt) mice. Additionally, an antidepressant-like effect was observed when DMI was administered to both 5-HT(1A)R KO and Wt mice. In conclusion: through the use of both genetic and pharmacological strategies, this study validates the extension of a protocol involving the DRL 72-s operant schedule of reinforcement as a behavioral model for the action of antidepressants in mice.</p>","PeriodicalId":88752,"journal":{"name":"The open neuropsychopharmacology journal","volume":"1 ","pages":"24-32"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845473/pdf/nihms145933.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28888132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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