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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Neuronal-Glial Interaction in a Triple-Transgenic Mouse Model of Alzheimer's Disease: Gene Ontology and Lithium Pathways

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Author(s):
Rocha, Nicole Kemberly R. [1] ; Themoteo, Rafael [2] ; Brentani, Helena [1] ; Forlenza, Orestes V. [2] ; De Paula, Vanessa De Jesus Rodrigues [1, 2]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Psicobiol LIM2, Dept & Inst Psiquiatria, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP, Lab Neurociencias LIM27, Dept Inst & Psiquiatria, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: FRONTIERS IN NEUROSCIENCE; v. 14, DEC 1 2020.
Web of Science Citations: 0
Abstract

Neuronal-glial interactions are critical for brain homeostasis, and disruption of this process may lead to excessive glial activation and inadequate pro-inflammatory responses. Abnormalities in neuronal-glial interactions have been reported in the pathophysiology of Alzheimer's disease (AD), where lithium has been shown to exert neuroprotective effects, including the up-regulation of cytoprotective proteins. In the present study, we characterize by Gene Ontology (GO) the signaling pathways related to neuronal-glial interactions in response to lithium in a triple-transgenic mouse model of AD (3x-TgAD). Mice were treated for 8 months with lithium carbonate (Li) supplemented to chow, using two dose ranges to yield subtherapeutic working concentrations (Li1, 1.0 g/kg; and Li2, 2.0 g/kg of chow), or with standard chow (Li0). The hippocampi were removed and analyzed by proteomics. A neuronal-glial interaction network was created by a systematic literature search, and the selected genes were submitted to STRING, a functional network to analyze protein interactions. Proteomics data and neuronal-glial interactomes were compared by GO using ClueGo (Cytoscape plugin) with p <= 0.05. The proportional effects of neuron-glia interactions were determined on three GO domains: (i) biological process; (ii) cellular component; and (iii) molecular function. The gene ontology of this enriched network of genes was further stratified according to lithium treatments, with statistically significant effects observed in the Li2 group (as compared to controls) for the GO domains biological process and cellular component. In the former, there was an even distribution of the interactions occurring at the following functions: ``positive regulation of protein localization to membrane,{''} ``regulation of protein localization to cell periphery,{''} ``oligodendrocyte differentiation,{''} and ``regulation of protein localization to plasma membrane.{''} In cellular component, interactions were also balanced for ``myelin sheath{''} and ``rough endoplasmic reticulum.{''} We conclude that neuronal-glial interactions are implicated in the neuroprotective response mediated by lithium in the hippocampus of AD-transgenic mice. The effect of lithium on homeostatic pathways mediated by the interaction between neurons and glial cells are implicated in membrane permeability, protein synthesis and DNA repair, which may be relevant for the survival of nerve cells amidst AD pathology. (AU)

FAPESP's process: 17/14418-8 - Effect of lithium on the telomeric length in cortical and hippocampal neurons treated with beta amyloid
Grantee:Rafael Martins Themoteo
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 11/19892-3 - Effects of lithium on the expression and activity of the enzymes Phospholipase A2 and glycogen synthase kinase 3B and its relation to the phosphorylation state of Tau protein
Grantee:Vanessa de Jesus Rodrigues de Paula
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/01302-9 - Direct and indirect pathways of glycogen synthase kinase 3B inhibition by lithium in culture of neurons
Grantee:Vanessa de Jesus Rodrigues de Paula
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 09/52825-8 - Neurobiology of Alzheimer's disease: risk markers, prognosis and therapeutic response
Grantee:Wagner Farid Gattaz
Support type: Research Projects - Thematic Grants
FAPESP's process: 18/08621-8 - Influence of lithium in neuron-glia interaction in hippocampal neurons
Grantee:Nicole Kemberly Ribeiro Rocha
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 14/50873-3 - INCT 2014: National Institute of Biomarkers in Neuropsychiatry
Grantee:Wagner Farid Gattaz
Support type: Research Projects - Thematic Grants