Browsing by Author "Noches, Veronica"

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    Hypothyroidism in the Adult Rat Causes Incremental Changes in Brain-Derived Neurotrophic Factor, Neuronal and Astrocyte Apoptosis, Gliosis, and Deterioration of Postsynaptic Density
    (MARY ANN LIEBERT, INC, 2012) Cortes, Claudia; Eugenin, Eliseo; Aliaga, Esteban; Carreno, Leandro J.; Bueno, Susan M.; Gonzalez, Pablo A.; Gayol, Silvina; Naranjo, David; Noches, Veronica; Marassi, Michelle P.; Rosenthal, Doris; Jadue, Cindy; Ibarra, Paula; Keitel, Cecilia; Wohllk, Nelson; Court, Felipe; Kalergis, Alexis M.; Riedel, Claudia A.
    Background: Adult hypothyroidism is a highly prevalent condition that impairs processes, such as learning and memory. Even though tetra-iodothyronine (T-4) treatment can overcome the hypothyroidism in the majority of cases, it cannot fully recover the patient's learning capacity and memory. In this work, we analyzed the cellular and molecular changes in the adult brain occurring with the development of experimental hypothyroidism.
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    Pilocarpine-induced seizures associate with modifications of LSD1/CoREST/HDAC1/2 epigenetic complex and repressive chromatin in mice hippocampus
    (2021) Noches, Veronica; Rivera, Carlos; Gonzalez, Marcela P.; Merello, Gianluca; Olivares-Costa, Montserrat; Estela Andres, Maria
    Epilepsy is a neurological disorder of genetic or environmental origin characterized by recurrent spontaneous seizures. A rodent model of temporal lobe epilepsy is induced by a single administration of pilocarpine, a nonselective cholinergic muscarinic receptor agonist. The molecular changes associated with pilocarpine-induced seizures are still poorly described. Epigenetic multiprotein complexes that regulate gene expression by changing the structure of chromatin impose transcriptional memories. Among the epigenetic enzymes relevant to the epileptogenic process is lysine-specific demethylase 1 (LSD1, KDM1A), which regulates the expression of genes that control neuronal excitability. LSD1 forms complexes with the CoREST family of transcriptional corepressors, which are molecular bridges that bring HDAC1/2 and LSD1 enzymes to deacetylate and demethylate the tail of nucleosomal histone H3. To test the hypothesis that LSD1-complexes are involved in initial modifications associated with pilocarpine-induced epilepsy, we studied the expression of main components of LSD1-complexes and the associated epigenetic marks on isolated neurons and the hippocampus of pilocarpine-treated mice. Using a single injection of 300 mg/kg of pilocarpine and after 24 h, we found that protein levels of LSD1, CoREST2, and HDAC1/2 increased, while CoREST1 decreased in the hippocampus. In addition, we observed increased histone H3 lysine 9 di- and trimethylation (H3K9me2/3) and decreased histone H3 lysine 4 di and trimethylation (H3K4me2/3). Similar findings were observed in cultured hippocampal neurons and HT-22 hippocampal cell line treated with pilocarpine. In conclusion, our data show that muscarinic receptor activation by pilocarpine induces a global repressive state of chromatin and prevalence of LSD1-CoREST2 epigenetic complexes, modifications that could underlie the pathophysiological processes leading to epilepsy.
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    Unveiling RCOR1 as a rheostat at transcriptionally permissive chromatin
    (2022) Rivera, Carlos; Lee, Hun-Goo; Lappala, Anna; Wang, Danni; Noches, Veronica; Olivares-Costa, Montserrat; Sjoberg-Herrera, Marcela; Lee, Jeannie T.; Andres, Maria Estela
    The classical neuronal-gene corepressor RCOR1/CoREST is paradoxically enriched in transcriptionally active chromatin. Here the authors show RCOR1 is recruited during promoter-proximal pausing and negatively regulates the nascent-transcript synthesis. They also show that an RCOR1-LSD1- HDAC1 complex removes lysine acetylation from RNA polymerase II to repress transcription.