Project description:Phagocytosis of synaptic debris by microglia is critical for CNS development and homeostasis. Less well understood are microglial functions in injured adult brain, where their presumed role is clearance of neuronal debris. Assay of this process is challenging, because the resulting peripheral myeloid-cell engraftment is difficult to dissociate from microglial clearance. The model used here, optic nerve crush injury in adult mouse, stimulates rapid engulfment of synaptic material by microglia residing in the lateral geniculate nucleus (LGN), sufficiently distant from the injury to preclude peripheral-cell engraftment. Pre-injury pharmacological depletion of microglia causes post-injury accumulation of synaptic debris, suggesting that these, not astrocytes, are the dominant post-injury phagocytes. Genetic and pharmacological manipulations revealed that neuronal activity, which regulates microglial engulfment of synaptic debris in development, does not do so in post-injury synaptic material clearance in adulthood, where such clearance depends instead on axonal integrity. RNAseq reveals C1q involvement in clearance of debris by LGN-resident microglia, supporting our finding of its impaired clearance in C1qa-/- and Itgam-/- mice. Our results demonstrate how neurodegenerative debris is cleared by microglial phagocytosis, and offer a model for assaying microglial phagocytic activity and studying its mechanisms and physiological roles.

2018-06-07 | GSE107635 | GEO

Multi-Modal Signatures of Tau Pathology, Neuronal Fiber Integrity, and Functional Connectivity in Traumatic Brain Injury.

Project description: Not available

| S-EPMC6857466 | biostudies-literature

Neuronal Pentraxin 1 Promotes Hypoxic-Ischemic Neuronal Injury by Impairing Mitochondrial Biogenesis via Interactions With Active Bax[6A7] and Mitochondrial Hexokinase II.

Project description: Not available

| S-EPMC8191073 | biostudies-literature

The structural integrity of mitochondrial DNA reveals new molecular perspectives for early diagnosis of colorectal cancer

Project description:Interventions: Group 1: The project aims to: Statistically compare the fragment length of cell-free DNA in the blood plasma of 80 patients with a confirmed diagnosis of colorectal carcinoma in stages I-IV with the cfDNA fragment lengths of 50 healthy subjects. For this purpose, residual amounts of blood plasma samples are used, which are collected anyway as part of theroutine examinations. Cell-free DNA was isolated from the blood plasma and the fragment lengths are measured using qPCR. The project ends with the publication of the data. Group 2: Statistically compare the fragment length of cell-free DNA in the blood plasma of 50 healthy subjects with 80 patients with a confirmed diagnosis of colorectal carcinoma in stages I-IV. The plasma samples from healthy volunteers were purchased (Central Biohub GmbH). Primary outcome(s): The aim of this study is: 1) to analyze total cfDNA concentration in CRC patients with different histopathological stages (UICC I-IV). 2) to address the question whether the integrity index of cfDNA increases in CRC patients as a result of elevated necrotic degradation processes. Therefore, we intended to quantify short and long fragments of cfDNA via qPCR independent from total cfDNA levels by using equal template concentrations for CRC patients and healthy individuals. This approach may help to understand whether previously described diagnostic markers are either increased, decreased or unaltered in blood plasma of CRC patients compared to healthy individuals. Study Design: Allocation: ; Masking: ; Control: ; Assignment: ; Study design purpose: basic science

| 2754663 | ecrin-mdr-crc

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