RT Journal Article
T1 miRNA-132/212 Deficiency Disrupts Selective Corticosterone Modulation of Dorsal vs. Ventral Hippocampal Metaplasticity
A1 Kouhnavardi, Shima
A1 Cabatic, Maureen
A1 Mañas-Padilla, María del Carmen
A1 Malabanan, Marife-Astrid
A1 Smani, Tarik
A1 Cicvaric, Ana
A1 Muñoz Aranzalez, Edison Alejandro
A1 Koenig, Xavier
A1 Urban, Ernst
A1 Lubec, Gert
A1 Castilla-Ortega, María Estela
A1 Monje, Francisco
K1 Cortisol
AB Cortisol is a potent human steroid hormone that plays key roles in the central nervous system, influencing processes such as brain neuronal synaptic plasticity and regulating the expression of emotional and behavioral responses. The relevance of cortisol stands out in the disease, as its dysregulation is associated with debilitating conditions such as Alzheimer’s Disease, chronic stress, anxiety and depression. Among other brain regions, cortisol importantly influences the function of the hippocampus, a structure central for memory and emotional information processing. The mechanisms fine-tuning the different synaptic responses of the hippocampus to steroid hormone signaling remain, however, poorly understood. Using ex vivo electrophysiology and wild type (WT) and miR-132/miR-212 microRNAs knockout (miRNA-132/212−/−) mice, we examined the effects of corticosterone (the rodent’s equivalent to cortisol in humans) on the synaptic properties of the dorsal and ventral hippocampus. In WT mice, corticosterone predominantly inhibited metaplasticity in the dorsal WT hippocampi, whereas it significantly dysregulated both synaptic transmission and metaplasticity at dorsal and ventral regions of miR–132/212−/− hippocampi. Western blotting further revealed significantly augmented levels of endogenous CREB and a significant CREB reduction in response to corticosterone only in miR–132/212−/− hippocampi. Sirt1 levels were also endogenously enhanced in the miR–132/212−/− hippocampi but unaltered by corticosterone, whereas the levels of phospo-MSK1 were only reduced by corticosterone in WT, not in miR–132/212−/− hippocampi. In behavioral studies using the elevated plus maze, miRNA-132/212−/− mice further showed reduced anxiety-like behavior. These observations propose miRNA-132/212 as potential region-selective regulators of the effects of steroid hormones on hippocampal functions, thus likely fine-tuning hippocampus-dependent memory and emotional processing.
YR 2023
FD 2023
LK https://hdl.handle.net/10630/28776
UL https://hdl.handle.net/10630/28776
LA eng
NO Kouhnavardi, S., Cabatic, M., Mañas-Padilla, M. C., Malabanan, M. A., Smani, T., Cicvaric, A., ... & Monje, F. J. (2023). miRNA-132/212 Deficiency Disrupts Selective Corticosterone Modulation of Dorsal vs. Ventral Hippocampal Metaplasticity. International Journal of Molecular Sciences, 24(11), 9565.
NO Center for Physiology and Pharmacology, Department of Neurophysiology and Neuropharmacology, Medical University of Vienna, 1090 Vienna, AustriaInstituto de Investigación Biomédica de Málaga-IBIMA, 29590 Málaga, SpainDepartment of Medical Physiology and Biophysics, University of Seville, 41013 Seville, SpainDominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY 10461, USADepartment for Pharmaceutical Sciences, Josef-Holaubek-Platz 2, 2D 303, 1090 Vienna, AustriaProgramme for Proteomics, Paracelsus Medical University, 5020 Salzburg, AustriaPartial funding for open access charge: Universidad de Málaga / CBUA
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026