Fine-tuning the pi3k/akt signaling pathway intensity by sex and genotype-load : sex-dependent homozygotic threshold for somatic growth but feminization of anxious phenotype in middle-aged pdk1 k465e knock-in and heterozygous mice
Santana-Santana, Mikel (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Bayascas Ramírez, José Ramón (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Gimenez-Llort, Lydia (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2021
Resum:	According to the Research Domain Criteria (RDoC), phenotypic differences among disorders may be explained by variations in the nature and degree of neural circuitry disruptions and/or dysfunctions modulated by several biological and environmental factors. We recently demonstrated the in vivo behavioral translation of tweaking the PI3K/Akt signaling, an essential pathway for regulating cellular processes and physiology, and its modulation through aging. Here we describe, for the first time, the in vivo behavioral impact of the sex and genetic-load tweaking this pathway. The anxiety-like phenotypes of 61 mature (11-14-month-old) male and female PDK1 K465E knock-in, heterozygous, and WT mice were studied. Forced (open-field) anxiogenic environmental conditions were sensitive to detect sex and genetic-load differences at middle age. Despite similar neophobia and horizontal activity among the six groups, females exhibited faster ethograms than males, with increased thigmotaxis, increased wall and bizarre rearing. Genotype-load unveiled increased anxiety in males, resembling female performances. The performance of mutants in naturalistic conditions (marble test) was normal. Homozygotic-load was needed for reduced somatic growth only in males. Factor interactions indicated the complex interplay in the elicitation of different negative valence system's items and the fine-tuning of PI3K/Akt signaling pathway intensity by genotype-load and sex.
Ajuts:	Ministerio de Economía y Competitividad SAF2014-52813-R
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	RDoC ; PI3K/Akt ; Signaling pathway ; Sex ; Genetic load ; Fine tuning ; Anxiety ; Aging
Publicat a:	Biomedicines, Vol. 9 Núm. 7 (july 2021) , p. 747, ISSN 2227-9059

DOI: 10.3390/biomedicines9070747
PMID: 34203450

12 p, 2.0 MB

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