ArticleBiomedicines2021
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.
Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
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- The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.International journal of molecular sciences · 2024Article
- Neural Correlates and Molecular Mechanisms of Memory and Learning.International journal of molecular sciences · 2024Article
- From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment.Cells · 2023Review
- Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models.International journal of molecular sciences · 2023Article
- The role of SIRT2 inhibition on the aging process of brain in male rats.Aging brain · 2023Article
- Integrating Armchair, Bench, and Bedside Research for Behavioral Neurology and Neuropsychiatry: Editorial.Biomedicines · 2022Article
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- Editorial of Special Issue 'Dissecting Neurological and Neuropsychiatric Diseases: Neurodegeneration and Neuroprotection'.International journal of molecular sciences · 2022Article
- Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer's Disease.Cells · 2022Review
- Article
- Systems Analysis Reveals Ageing-Related Perturbations in Retinoids and Sex Hormones in Alzheimer's and Parkinson's Diseases.Biomedicines · 2021Article
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3 authors.
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Abstract
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.
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