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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

Authors: Henna Martiskainen, Kaisa M. A. Paldanius, Teemu Natunen, Mari Takalo, Mikael Marttinen, Stina Leskelä, Nadine Huber, Petra Mäkinen, Enni Bertling, Hiramani Dhungana, Mikko Huuskonen, Paavo Honkakoski, Pirta Hotulainen, Kirsi Rilla, Jari Koistinaho, Hilkka Soininen, Tarja Malm, Annakaisa Haapasalo, Mikko Hiltunen

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

DHCR24, involved in the de novo synthesis of cholesterol and protection of neuronal cells against different stress conditions, has been shown to be selectively downregulated in neurons of the affected brain areas in Alzheimer’s disease.

Methods

Here, we investigated whether the overexpression of DHCR24 protects neurons against inflammation-induced neuronal death using co-cultures of mouse embryonic primary cortical neurons and BV2 microglial cells upon acute neuroinflammation. Moreover, the effects of DHCR24 overexpression on dendritic spine density and morphology in cultured mature mouse hippocampal neurons and on the outcome measures of ischemia-induced brain damage in vivo in mice were assessed.

Results

Overexpression of DHCR24 reduced the loss of neurons under inflammation elicited by LPS and IFN-γ treatment in co-cultures of mouse neurons and BV2 microglial cells but did not affect the production of neuroinflammatory mediators, total cellular cholesterol levels, or the activity of proteins linked with neuroprotective signaling. Conversely, the levels of post-synaptic cell adhesion protein neuroligin-1 were significantly increased upon the overexpression of DHCR24 in basal growth conditions. Augmentation of DHCR24 also increased the total number of dendritic spines and the proportion of mushroom spines in mature mouse hippocampal neurons. In vivo, overexpression of DHCR24 in striatum reduced the lesion size measured by MRI in a mouse model of transient focal ischemia.

Conclusions

These results suggest that the augmentation of DHCR24 levels provides neuroprotection in acute stress conditions, which lead to neuronal loss in vitro and in vivo.
Appendix
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Metadata
Title
DHCR24 exerts neuroprotection upon inflammation-induced neuronal death
Authors
Henna Martiskainen
Kaisa M. A. Paldanius
Teemu Natunen
Mari Takalo
Mikael Marttinen
Stina Leskelä
Nadine Huber
Petra Mäkinen
Enni Bertling
Hiramani Dhungana
Mikko Huuskonen
Paavo Honkakoski
Pirta Hotulainen
Kirsi Rilla
Jari Koistinaho
Hilkka Soininen
Tarja Malm
Annakaisa Haapasalo
Mikko Hiltunen
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0991-6

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