Licht-Mayer, Simon;
Campbell, Graham R;
Mehta, Arpan R;
McGill, Katie;
Symonds, Alex;
Al-Azki, Sarah;
Pryce, Gareth;
... Mahad, Don J; + view all
(2023)
Axonal response of mitochondria to demyelination and complex IV activity within demyelinated axons in experimental models of multiple sclerosis.
Neuropathology and Applied Neurobiology
, 49
(1)
, Article e12851. 10.1111/nan.12851.
Preview |
Text
Neuropathology Appl Neurobio - 2022 - Licht‐Mayer - Axonal response of mitochondria to demyelination and complex IV.pdf Download (2MB) | Preview |
Abstract
AIMS: Axonal injury in multiple sclerosis (MS) and experimental models is most frequently detected in acutely demyelinating lesions. We recently reported a compensatory neuronal response, where mitochondria move to the acutely demyelinated axon and increase the mitochondrial content following lysolecithin-induced demyelination. We termed this homeostatic phenomenon, which is also evident in MS, the axonal response of mitochondria to demyelination (ARMD). The aim of this study is to determine whether ARMD is consistently evident in experimental demyelination and how its perturbation relates to axonal injury. METHODS: In the present study, we assessed axonal mitochondrial content as well as axonal mitochondrial respiratory chain complex IV activity (cytochrome c oxidase or COX) of axons and related these to axonal injury in nine different experimental disease models. We used immunofluorescent histochemistry as well as sequential COX histochemistry followed by immunofluorescent labelling of mitochondria and axons. RESULTS: We found ARMD a consistent and robust phenomenon in all experimental disease models. The increase in mitochondrial content within demyelinated axons, however, was not always accompanied by a proportionate increase in complex IV activity, particularly in highly inflammatory models such as experimental autoimmune encephalomyelitis (EAE). Axonal complex IV activity inversely correlated with the extent of axonal injury in experimental disease models. CONCLUSIONS: Our findings indicate that ARMD is a consistent and prominent feature and emphasise the importance of complex IV activity in the context of ARMD, especially in autoimmune inflammatory demyelination, paving the way for the development of novel neuroprotective therapies.
| Type: | Article |
|---|---|
| Title: | Axonal response of mitochondria to demyelination and complex IV activity within demyelinated axons in experimental models of multiple sclerosis |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/nan.12851 |
| Publisher version: | https://doi.org/10.1111/nan.12851 |
| Language: | English |
| Additional information: | Copyright © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | axon injury, complex IV, experimental demyelination, mitochondria, multiple sclerosis and neuroprotection |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10156636 |
Archive Staff Only
 |
View Item |
