Publications

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2 Publications visible to you, out of a total of 2
Repetitive concussions promote microglia-mediated engulfment of presynaptic excitatory input associated with cognitive dysfunction

Abstract (Expand)

Abstract Concussions are a current health concern and account for the vast majority of head trauma. While symptoms after a single impact are usually transient, repetitive concussions, as often occur …ften occur in sports, are responsible for persistent acute and chronic deficits. Here, we used a model of bilateral midline-centered concussions in mice to show that repetitive concussions selectively induce impairments in learning ability compared to single-impact injuries. Since microglial cells and their activation are considered key factors in degenerative pathology after brain trauma, we examined their structure and function after single and repetitive concussions in the cortex underlying the concussions and in the hippocampus. We found that only repetitive concussions led to a significant long-lasting structural activation of microglia and an increase in microglia-mediated engulfment of presynaptic excitatory synapses, while the elimination of inhibitory synapses was not altered. Since the density of excitatory input did not change during the 6-week study period, we hypothesize that there is a turnover of excitatory synapses following repetitive concussion that can be compensated for, anatomically but not behaviorally.

Authors: Maryam Chahin, Julius Mutschler, Stephanie P. Dzhuleva, Clara Dieterle, Leidy Reyes Jimenez, Srijan Raj Bhattarai, Valerie Van Steenbergen, Florence M. Bareyre

Date Published: 28th Feb 2025

Publication Type: Journal Article

Targeting the TCA cycle can ameliorate widespread axonal energy deficiency in neuroinflammatory lesions

Abstract (Expand)

Abstract Inflammation in the central nervous system can impair the function of neuronal mitochondria and contributes to axon degeneration in the common neuroinflammatory disease multiple sclerosis (MS). …le sclerosis (MS). Here we combine cell-type-specific mitochondrial proteomics with in vivo biosensor imaging to dissect how inflammation alters the molecular composition and functional capacity of neuronal mitochondria. We show that neuroinflammatory lesions in the mouse spinal cord cause widespread and persisting axonal ATP deficiency, which precedes mitochondrial oxidation and calcium overload. This axonal energy deficiency is associated with impaired electron transport chain function, but also an upstream imbalance of tricarboxylic acid (TCA) cycle enzymes, with several, including key rate-limiting, enzymes being depleted in neuronal mitochondria in experimental models and in MS lesions. Notably, viral overexpression of individual TCA enzymes can ameliorate the axonal energy deficits in neuroinflammatory lesions, suggesting that TCA cycle dysfunction in MS may be amendable to therapy.

Authors: Yi-Heng Tai, Daniel Engels, Giuseppe Locatelli, Ioanna Emmanouilidis, Caroline Fecher, Delphine Theodorou, Stephan A. Müller, Simon Licht-Mayer, Mario Kreutzfeldt, Ingrid Wagner, Natalia Prudente de Mello, Sofia-Natsouko Gkotzamani, Laura Trovò, Arek Kendirli, Almir Aljović, Michael O. Breckwoldt, Ronald Naumann, Florence M. Bareyre, Fabiana Perocchi, Don Mahad, Doron Merkler, Stefan F. Lichtenthaler, Martin Kerschensteiner, Thomas Misgeld

Date Published: 10th Jul 2023

Publication Type: Journal Article

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