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Opiate abuse and addiction have become a worldwide epidemic with great societal and financial burdens, highlighting a critical need to understand the neurobiology of opiate addiction. Although several studies have focused on drug-dependent changes in neurons, the role of glia in opiate addiction remains largely unstudied. RNA sequencing pathway analysis from the prefrontal cortex (PFC) of male rats revealed changes in several genes associated with oligodendrocyte differentiation and maturation following heroin self-administration. Among these genes changed was Sox10, which is regulated, in part, by the chromatin remodeler BRG1/SMARCA4. To directly test the functional role of Sox10 in mediating heroin-induced behavioral plasticity, we selectively overexpressed Sox10 and BRG1 in the PFC. Overexpression of either Sox10 or BRG1 decreased the motivation to obtain heroin infusions in a progressive ratio test without altering the acquisition or maintenance of heroin self-administration. These data demonstrate a critical, and perhaps compensatory, role of Sox10 and BRG1 in oligodendrocytes in regulating the motivation for heroin.
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http://dx.doi.org/10.1038/npp.2017.303 | DOI Listing |
Head Neck Pathol
July 2025
Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA.
Purpose: SMARCA4-deficient high-grade malignancies are increasingly recognized across various anatomic sites, namely the genitourinary tract thorax, gastrointestinal tract, head and neck, and central nervous system. Within the head and neck region, the sinonasal tract is most commonly affected. These tumors are aggressive, often presenting with local or distant metastases at diagnosis, and median survival ranges from 4 to 7 months.
View Article and Find Full Text PDFTurk Patoloji Derg
May 2024
Department of Pathology, Basavatarakam Indo American Cancer Hospital & Research Institute, HYDERABAD, INDIA.
Objective: SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a highly malignant neoplasm with an undifferentiated or rhabdoid phenotype, posing a diagnostic challenge. This case report aims to create awareness about this rare neoplasm while dealing with cases presenting with undifferentiated morphology.
Case Report: A 55-year-old gentleman with constitutional symptoms and lymphadenopathy.
J Cutan Pathol
April 2024
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm (SD-UMN) is a rare and recently described entity characterized by the loss of expression of the SMARCA4 (BRG1) protein, which is involved in chromatin remodeling. SD-UMN presents a diagnostic challenge due to its rarity and unique histopathological and immunohistochemical features. In this report, we present a case of primary cutaneous SD-UMN in a 67-year-old man who presented with a rapidly growing, ulcerated, and bleeding nodule on his right cheek.
View Article and Find Full Text PDFCell Rep
November 2023
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Equipe Labéllisée, "Ligue contre le Cancer 2022", BP 163, 67404 Illkirch Cedex, C.U. Strasbourg, France; Centre National de la Recherche Scientifique, UMR7104, 67404 Illkirch, France; Institut National de la Santé et de la Recherc
Super-enhancers (SEs) are stretches of enhancers ensuring a high level of expression of key genes associated with cell function. The identification of cancer-specific SE-driven genes is a powerful means for the development of innovative therapeutic strategies. Here, we identify a MITF/SOX10/TFIIH-dependent SE promoting the expression of BAHCC1 in a broad panel of melanoma cells.
View Article and Find Full Text PDFCancer Discov
December 2022
Depart-ments of Neuro-logy, Pediatrics, and Neurosurgery, University of California, San Francisco, San Francisco, California.
Epigenetic reprogramming drives tumorigenesis in pediatric H3K27M diffuse midline glioma (DMG) by altering the canonical functions of chromatin remodeling complexes. These studies (i) identified BRG1 (encoded by SMARCA4), the catalytic subunit of the mammalian SWI/SNF (BAF) chromatin remodeling complex, as a novel dependency in pediatric H3K27M glioma; (ii) investigated the molecular mechanisms underlying the maintenance of the progenitor state; and (iii) demonstrated efficacy for BRG1 inhibitors.The authors identified the BRG1 ATPase as a dependency in pediatric H3K27M-mutant DMG.
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