Cognitive and Emotional Symptoms Induced by Chronic Stress Are Regulated by EGR1 in a Subpopulation of Hippocampal Pyramidal Neurons.
Int J Mol Sci
; 24(4)2023 Feb 14.
Article
en En
| MEDLINE
| ID: mdl-36835243
Chronic stress is a core risk factor for developing a myriad of neurological disorders, including major depression. The chronicity of such stress can lead to adaptive responses or, on the contrary, to psychological maladaptation. The hippocampus is one of the most affected brain regions displaying functional changes in chronic stress. Egr1, a transcription factor involved in synaptic plasticity, is a key molecule regulating hippocampal function, but its role in stress-induced sequels has been poorly addressed. Emotional and cognitive symptoms were induced in mice by using the chronic unpredictable mild stress (CUMS) protocol. We used inducible double-mutant Egr1-CreERT2 x R26RCE mice to map the formation of Egr1-dependent activated cells. Results show that short- (2 days) or long-term (28 days) stress protocols in mice induce activation or deactivation, respectively, of hippocampal CA1 neural ensembles in an Egr1-activity-dependent fashion, together with an associated dendritic spine pathology. In-depth characterization of these neural ensembles revealed a deep-to-superficial switch in terms of Egr1-dependent activation of CA1 pyramidal neurons. To specifically manipulate deep and superficial pyramidal neurons of the hippocampus, we then used Chrna7-Cre (to express Cre in deep neurons) and Calb1-Cre mice (to express Cre in superficial neurons). We found that specific manipulation of superficial but not deep pyramidal neurons of the CA1 resulted in the amelioration of depressive-like behaviors and the restoration of cognitive impairments induced by chronic stress. In summary, Egr1 might be a core molecule driving the activation/deactivation of hippocampal neuronal subpopulations underlying stress-induced alterations involving emotional and cognitive sequels.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Psicológico
/
Cognición
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Células Piramidales
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Emociones
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Proteína 1 de la Respuesta de Crecimiento Precoz
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Región CA1 Hipocampal
Tipo de estudio:
Diagnostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2023
Tipo del documento:
Article
País de afiliación:
España
Pais de publicación:
Suiza