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#Microglia

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victorjavierlo

🧬 Excited to share findings from a collaboration on #Alzheimer's! 🧬 Our team contributed RNA-seq analysis to explore how FAAH inactivation influences neuroinflammation and microglial function. This study reveals a paradox: while FAAH inactivation enhances microglial activity, it also escalates inflammation in 5xFAD AD mice. Results could point to FAAH as a therapeutic target in AD! #Neuroinflammation #Microglia #Endocannabinoids #RNAseq #ScienceCollab #bioinformatics

onlinelibrary.wiley.com/doi/10

Public
Moritz Negwer

This is a FIJI plugin that can analyze branched structures in a broad range of settings. They started with Microglia, but apparently it's broadly applicable (also works with neurons and even corals). Looks useful for analyzing 2D images.

AutoMorFi: Automated Whole-image Morphometry in Fiji/ImageJ for Diverse Image Analysis Needs
Bouadi ... Tuan Leng Tay, preprint at biorxiv 2024
⁠biorxiv.org/content/10.1101/20

Figure 4: Diverse applications of AutoMorFi. (A) Comparative morphometric analysis of glial cells from different models. Representative widefield fluorescence and brightfield images of glial cells from experimental models (Drosophila astrocyte-like glia, hiPSCs-derived microglia, human microglia, and mouse microglia) and their corresponding whole-cell outlines. UMAPs of 1,100 glial cells clustered based on 47 morphometric parameters or model system. (B) Single object morphometric analysis. Representative widefield fluorescence images of MAP2-immunolabeled primary neurons (white) from Ube3a 2x transgenic and wildtype mice and their corresponding whole-cell and skeletonized traces with an example of an added pseudo-object (white arrowhead). Six of 33 morphometric parameters were significantly different between genotypes in unpaired t-tests: whole cell perimeter (p=0.0138), whole cell height (p=0.0270), whole cell minimum feret (p=0.0116), whole cell convex area (p=0.0177), perimeter to area ratio, and solidity (p=0.0351). N = 14 per group. (C) Acetylated-α-tubulin marker-specific morphometric and fluorescence intensity measurements. Representative widefield fluorescence images of Xenopus MCCs indicated by centrin4-cfp (grey) with varying levels of ciliation indicated by acetylated-α-tubulin (red) and whole-cell outline of the marker (yellow).
#neuroscience#microglia#imageanalysis
Public
Moritz Negwer

"Here, we show that microglia in the mediobasal hypothalamus (MBH) of mice actively engage in synaptic pruning during early life. Microglial phagocytic activity is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In particular, we show that microglia refine perineuronal nets (PNNs) within the neonatal MBH."

biorxiv.org/content/10.1101/20

bioRxiv · Microglia mediate the early-life programming of adult glucose controlMammalian glucose homeostasis is, in part, nutritionally programmed during early neonatal life, a critical window for the formation of synapses between hypothalamic glucoregulatory centers. Although microglia are known to prune synapses throughout the brain, their specific role in refining hypothalamic glucoregulatory circuits remains unknown. Here, we show that microglia in the mediobasal hypothalamus (MBH) of mice actively engage in synaptic pruning during early life. Microglial phagocytic activity is induced following birth, regresses upon weaning from maternal milk, and is exacerbated by feeding dams a high-fat diet while lactating. In particular, we show that microglia refine perineuronal nets (PNNs) within the neonatal MBH. Indeed, transiently depleting microglia before weaning (P6-16), but not afterward (P21-31), remarkably increased PNN abundance in the MBH. Furthermore, mice lacking microglia only from P6-16 had glucose intolerance due to impaired glucose-responsive pancreatic insulin secretion in adulthood, a phenotype not seen if microglial depletion occurred after weaning. Viral retrograde tracing revealed that this impairment is linked to a reduction in the number of neurons in specific hypothalamic glucoregulatory centers that synaptically connect to the pancreatic beta cell compartment. These findings show that microglia facilitate synaptic plasticity in the MBH during early life through a process that includes PNN refinement, to establish hypothalamic circuits that regulate adult glucose homeostasis. ### Competing Interest Statement The authors have declared no competing interest.
#neuroscience#microglia#metabolism
Public
Moritz Negwer

"Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aβ clearance and accumulation of amyloid plaques."

Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models
Wasén et al., Nature Communications 2024
doi.org/10.1038/s41467-024-476

#neuroscience#gutbacteria#microbiome
Public
Moritz Negwer

News to me: Local translation isn't limited to neurons, apparently also happens in glial processes. See here for #microglia:

Local translation in microglial processes is required for efficient phagocytosis
Vasek et al., Nature Neuroscience 2023
doi.org/10.1038/s41593-023-013

The accompanying news & views write-up has a useful overview figure: doi.org/10.1038/s41593-023-013

a, Microglial processes show levels of RLP10a and puromycin, indicating protein translation. The authors used a CX3CR1-Cre(ERt2)-TRAP mouse line, in which ribosomes are tagged with GFP in CX3CR1 cells (predominantly microglia), and RNA-sequencing analysis of whole cells and synaptosome-associated processes to identify a series of transcripts that were differentially associated with the microglial soma and processes. b, Blockade of translation reduced microglial process number and phagocytic cup formation, as well as bead engulfment. c, Analysis of transcripts was performed predominantly in microglial processes associated with the synaptosome and the neuropil; however, microglial processes are in dynamic interaction with a wide range of other cell types and compartments, such as blood vessels, astrocytes and axonal myelin. Therefore, future work will need to determine whether microglial processes in contact with these different structures possess the same set of enriched transcripts.
#neuroscience#glia#proteintranslation
Public
katch wreck

"We discuss preclinical evidence related to both neuronal & nonneuronal mechanisms that may be involved, touching upon the relevance of #interneurons, neuropeptides, & specific synaptic mechanisms in translating gamma stimulation into widespread neuronal activity within the brain. We also explore the roles of #microglia, #astrocytes, & the vasculature in mediating the beneficial effects of gamma stimulation on #brain function. Lastly, we examine upcoming clinical trials"

onlinelibrary.wiley.com/doi/10

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