DHCR24 exerts neuroprotection upon inflammation-induced neuronal death

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dc.contributor.author Martiskainen, Henna
dc.contributor.author Paldanius, Kaisa M A
dc.contributor.author Natunen, Teemu
dc.contributor.author Takalo, Mari
dc.contributor.author Marttinen, Mikael
dc.contributor.author Leskelä, Stina
dc.contributor.author Huber, Nadine
dc.contributor.author Mäkinen, Petra
dc.contributor.author Bertling, Enni
dc.contributor.author Dhungana, Hiramani
dc.contributor.author Huuskonen, Mikko
dc.contributor.author Honkakoski, Paavo
dc.contributor.author Hotulainen, Pirta
dc.contributor.author Rilla, Kirsi
dc.contributor.author Koistinaho, Jari
dc.contributor.author Soininen, Hilkka
dc.contributor.author Malm, Tarja
dc.contributor.author Haapasalo, Annakaisa
dc.contributor.author Hiltunen, Mikko
dc.date.accessioned 2017-11-12T05:40:37Z
dc.date.available 2017-11-12T05:40:37Z
dc.date.issued 2017-11-07
dc.identifier.citation Journal of Neuroinflammation. 2017 Nov 07;14(1):215
dc.identifier.uri http://hdl.handle.net/10138/228497
dc.description.abstract 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.
dc.publisher BioMed Central
dc.subject Alzheimer’s disease
dc.subject DHCR24/Seladin-1
dc.subject Neuroinflammation
dc.subject Neuroprotection
dc.title DHCR24 exerts neuroprotection upon inflammation-induced neuronal death
dc.date.updated 2017-11-12T05:40:38Z
dc.language.rfc3066 en
dc.rights.holder The Author(s).
dc.type.uri http://purl.org/eprint/entityType/ScholarlyWork
dc.type.uri http://purl.org/eprint/entityType/Expression
dc.type.uri http://purl.org/eprint/type/JournalArticle

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