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Autoren: Cuadrado, Diego Pascual
Wierczeiko, Anna
Hewel, Charlotte
Gerber, Susanne
Lutz, Beat
Titel: Dichotomic hippocampal transcriptome after glutamatergic vs. GABAergic deletion of the cannabinoid CB1 receptor
Online-Publikationsdatum: 26-Jul-2021
Sprache des Dokuments: Englisch
Zusammenfassung/Abstract: Brain homeostasis is the dynamic equilibrium whereby physiological parameters are kept actively within a specific range. The homeostatic range is not fixed and may change throughout the individual's lifespan, or may be transiently modified in the presence of severe perturbations. The endocannabinoid system has emerged as a safeguard of homeostasis, e.g., it modulates neurotransmission and protects neurons from prolonged or excessively strong activation. We used genetically engineered mouse lines that lack the cannabinoid type-1 receptor (CB1) either in dorsal telencephalic glutamatergic or in forebrain GABAergic neurons to create new allostatic states, resulting from alterations in the excitatory/inhibitory (E/I) balance. Previous studies with these two mouse lines have shown dichotomic results in the context of behavior, neuronal morphology, and electrophysiology. Thus, we aimed at analyzing the transcriptomic profile of the hippocampal CA region from these mice in the basal condition and after a mild behavioral stimulation (open field). Our results provide insights into the gene networks that compensate chronic E/I imbalances. Among these, there are differentially expressed genes involved in neuronal and synaptic functions, synaptic plasticity, and the regulation of behavior. Interestingly, some of these genes, e.g., Rab3b, Crhbp, and Kcnn2, and related pathways showed a dichotomic expression, i.e., they are up-regulated in one mutant line and down-regulated in the other one. Subsequent interrogation on the source of the alterations at transcript level were applied using exon-intron split analysis. However, no strong directions toward transcriptional or post-transcriptional regulation comparing both mouse lines were observed. Altogether, the dichotomic gene expression observed and their involved signaling pathways are of interest because they may act as “switches” to modulate the directionality of neural homeostasis, which then is relevant for pathologies, such as stress-related disorders and epilepsy.
DDC-Sachgruppe: 610 Medizin
610 Medical sciences
Veröffentlichende Institution: Johannes Gutenberg-Universität Mainz
Organisationseinheit: FB 04 Medizin
Veröffentlichungsort: Mainz
ROR: https://ror.org/023b0x485
DOI: http://doi.org/10.25358/openscience-6208
Version: Published version
Publikationstyp: Zeitschriftenaufsatz
Weitere Angaben zur Dokumentart: Scientific article
Nutzungsrechte: CC BY
Informationen zu den Nutzungsrechten: https://creativecommons.org/licenses/by/4.0/
Zeitschrift: Frontiers in synaptic neuroscience
13
Seitenzahl oder Artikelnummer: 660718
Verlag: Frontiers Research Foundation
Verlagsort: Lausanne
Erscheinungsdatum: 2021
ISSN: 1663-3563
URL der Originalveröffentlichung: https://doi.org/10.3389/fnsyn.2021.660718
DOI der Originalveröffentlichung: 10.3389/fnsyn.2021.660718
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