Microglial Metamorphosis in Three Dimensions in Virus Limbic Encephalitis: An Unbiased Pictorial Representation Based on a Stereological Sampling Approach of Surveillant and Reactive Microglia

Microglia influence pathological progression in neurological diseases, reacting to insults by expressing multiple morphofunctional phenotypes. However, the complete morphological spectrum of reactive microglia, as revealed by three-dimensional microscopic reconstruction, has not been detailed in vir...

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Bibliographic Details
Published in:Brain sciences 2021-07, Vol.11 (8), p.1009
Main Authors: da Silva Creão, Leonardo Sávio, Neto, João Bento Torres, de Lima, Camila Mendes, dos Reis, Renata Rodrigues, de Sousa, Aline Andrade, dos Santos, Zaire Alves, Diniz, José Antonio Picanço, Diniz, Daniel Guerreiro, Diniz, Cristovam Wanderley Picanço
Format: Article
Language:English
Subjects:
Albinism
albino swiss mice
Brain
Branches
Cluster analysis
Cytology
Encephalitis
Functional morphology
Gene expression
Laboratory animals
Metamorphosis
Microglia
Morphology
Multivariate analysis
Neurological diseases
Phenotypes
Physiology
piry virus
quantitative neuropathology
Statistical analysis
Surveillance
viral encephalitis
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Summary:Microglia influence pathological progression in neurological diseases, reacting to insults by expressing multiple morphofunctional phenotypes. However, the complete morphological spectrum of reactive microglia, as revealed by three-dimensional microscopic reconstruction, has not been detailed in virus limbic encephalitis. Here, using an anatomical series of brain sections, we expanded on an earlier Piry arbovirus encephalitis study to include CA1/CA2 and assessed the morphological response of homeostatic and reactive microglia at eight days post-infection. Hierarchical cluster and linear discriminant function analyses of multimodal morphometric features distinguished microglial morphology between infected animals and controls. For a broad representation of the spectrum of microglial morphology in each defined cluster, we chose representative cells of homeostatic and reactive microglia, using the sum of the distances of each cell in relation to all the others. Based on multivariate analysis, reactive microglia of infected animals showed more complex trees and thicker branches, covering a larger volume of tissue than in control animals. This approach offers a reliable representation of microglia dispersion in the Euclidean space, revealing the morphological kaleidoscope of surveillant and reactive microglia morphotypes. Because form precedes function in nature, our findings offer a starting point for research using integrative methods to understand microglia form and function.
ISSN:2076-3425
2076-3425
DOI:10.3390/brainsci11081009