This study examined the effects of thalamo-striatal deafferentation on preprotachykinin and preproenkephalin mRNA expression in the rat neostriatum, using quantitative in situ hybridization histochemistry. Unilateral ibotenate-induced intralaminar thalamic lesion produced a significant decrease in preproenkephalin mRNA levels (-27%) restricted to the ipsilateral striatum at 5 days post-lesion. At 12 days post-lesion, significant decreases in striatal preproenkephalin mRNA expression were found on both brain sides. This post-lesional response was more pronounced in the ipsilateral (-32%) than contralateral (-18%) striatum. All these changes were homogeneously distributed between the dorsolateral and ventromedial parts of the striatum. In parallel, no significant change in preprotachykinin mRNA expression was found at either 5 or 12 days after thalamic lesion, when considering the striatum as a whole. However, at 5 days post-lesion, the regional analysis revealed a slight decrease (-17%) in preprotachykinin mRNA expression, confined to the dorsolateral part of the ipsilateral striatum. These results show that thalamic lesion preferentially affects preproenkephalin vs. preprotachykinin gene expression in the striatum, suggesting, at the first site, a predominant influence of thalamo-striatal inputs on the enkephalin-containing striato-pallidal pathway. However, given that the thalamo-striatal projection is strictly ipsilateral, the bilateralization of the down-regulation of preproenkephalin mRNA expression at 12 days post-lesion suggests an involvement of interhemispheric adaptive mechanisms via cortical networks.
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http://dx.doi.org/10.1016/s0169-328x(98)00098-9 | DOI Listing |
J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Pathology, 906 Hospital of Joint Logistic Support Force of PLA, Ningbo, Zhejiang, China.
Objective: To investigate the effects and mechanisms of miRNA 221 on myocardial ischemia/reperfusion injury (MIRI) in mice through the regulation of phospholamban (PLB) expression.
Methods: The MIRI mouse model was created and mice were divided into sham, MIRI, MIRI+ 221, and MIRI+ scr groups, with miRNA 221 overexpression induced in the myocardium of MIRI mice by targeted myocardial injection. Quantitative RT-PCR analysis was performed to observe the variation in miRNA 221, PLB, SERCA2, RYR2, NCX1, Cyt C and caspase 3 mRNA levels in myocardium, while Western blot assessed the levels of PLB, p-PLB (Ser16), p-PLB (Thr17), SERCA2, RYR2, NCX1, Cyt C and caspase 3 proteins.
PLoS Genet
January 2025
Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.
Stem cell pluripotency gene Sox2 stimulates expression of proneural basic-helix-loop-helix transcription factor Atoh1. Sox2 is necessary for the development of cochlear hair cells and binds to the Atoh1 3' enhancer to stimulate Atoh1 expression. We show here that Sox2 deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after Sox2 knockout early in gestation.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Reproductive Medicine, Guangzhou Women and Children's Medical center Liuzhou Hospital, Liuzhou, Guangxi, China.
Endometrial cancer (UCEC) is the most prevalent gynecological malignancy in high-income countries, and its incidence is rising globally. Although early-stage UCEC can be treated with surgery, advanced cases have a poor prognosis, highlighting the need for effective molecular biomarkers to improve diagnosis and prognosis. In this study, we analyzed mRNA and miRNA sequencing data from UCEC tissues and adjacent non-cancerous tissues from the TCGA database.
View Article and Find Full Text PDFPLoS One
January 2025
Biomedical Sciences Research Institute, Centre for Genomic Medicine, Ulster University, Coleraine, Northern Ireland, United Kingdom.
Pseudoexfoliation glaucoma is a severe form of secondary open angle glaucoma and is associated with activation of the TGF-β pathway by TGF-β1. MicroRNAs (miRNAs) are small non-coding RNA species that are involved in regulation of mRNA expression and translation. To investigate what glaucomatous changes occur in the trabecular meshwork and how these changes may be regulated by miRNAs, we performed a bioinformatics analysis resulting in a miRNA-mRNA interactome.
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