Microglial Morphometric Parameters Correlate With the Expression Level of IL-1β, and Allow Identifying Different Activated Morphotypes

Abstract

Microglia are the resident macrophages in the brain. Traditionally, two forms of microglia have been described: one considered as a resting/surveillant state in which cells have a highly branched morphology, and another considered as an activated state in which they acquire a de-ramified or amoeboid form. However, many studies describe intermediate microglial morphologies which emerge during pathological processes. Since microglial form and function are closely related, it is of interest to correlate microglial morphology with the extent of its activation. To address this issue, we used a rat model of neuroinflammation consisting in a single injection of the enzyme neuraminidase (NA) within the lateral ventricle. Sections from NA-injected animals were co-immunolabeled with the microglial marker IBA1 and the cytokine IL-1β, which highlight features of the cell’s shape and inflammatory activation, respectively. Activated (IL-1β positive) microglial cells were sampled from the dorsal hypothalamus nearby the third ventricle. Images of single microglial cells were processed in two different ways to obtain (1) an accurate measure of the level of expression of IL-1β (indicating the degree of activation), and (2) a set of 15 morphological parameters to quantitatively and objectively describe the cell’s shape. A simple regression analysis revealed a dependence of most of the morphometric parameters on IL-1β expression, demonstrating that the morphology of microglial cells changes progressively with the degree of activation. Moreover, a hierarchical cluster analysis pointed out four different morphotypes of activated microglia, which are characterized not only by morphological parameters values, but also by specific IL-1β expression levels. Thus, these results demonstrate in an objective manner that the activation of microglial cells is a gradual process, and correlates with their morphological change. Even so, it is still possible to categorize activated cells according to their morphometric parameters, each category presenting a different activation degree. The physiological relevance of those activated morphotypes is an issue worth to be assessed in the future.

Transcriptomic and morphological response of SIM-A9 mouse microglia to carbon nanotube neuro-sensors

“…1, C to F). These projections are known to be responsible for increasing microglial cell surface area within the brain microenvironment as a result of microglial activation and are typically found at the tips of microglial processes (28,29). Conversely, we observe that (GT)6-SWCNT exposure promoted growth of projections along the entire length of the cell branches, not only at the tip of microglial processes (Fig.…”

Genistein-3′-sodium Sulfonate Attenuates Cerebral Ischemia/reperfusion Injury in Rats by Down-regulating Microglial M1 Polarization Through α7nAChR-mediated Inhibition of NF-κb Signaling Pathway 

“…Our results showed that microglia in ischemic penumbra regions was signi cantly activated, showing a rod-shaped morphology with a large cell body [44] . In comparison, GSS treatment signi cantly inhibited the activation of microglia in ischemic penumbra regions where most microglia were rami ed shape as showing in sham rats [45,46] .…”

Microglial and peripheral immune priming is partially sexually dimorphic in adolescent mouse offspring exposed to maternal high-fat diet

“…The increased microglial solidity may represent a change in the distribution of the arborization, particularly a decreased distance between branches which would reflect a more convex-like shape. Others also hypothesized that an increase of the solidity value occurs during the morphological shift from a ramified to an amoeboid shape upon neuroinflammatory insults and represents a de-ramified or bushy morphology [103,104], a phenotype seen upon exposure to stress [105]. In a bacterial MIA mouse model, microglia were previously shown to shift their morphology to an ameboid shape in adolescent (PND40) offspring amygdala [106].…”