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DHCR24 exerts neuroprotection upon inflammation-induced neuronal death
- Source :
- Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-16 (2017), Journal of Neuroinflammation
- Publication Year :
- 2017
- Publisher :
- BMC, 2017.
-
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.<br />published version<br />peerReviewed
- Subjects :
- Male
0301 basic medicine
Oxidoreductases Acting on CH-CH Group Donors
Dendritic spine
DHCR24/Seladin-1
Immunology
Inflammation
Striatum
Brain damage
Biology
Hippocampal formation
Hippocampus
Neuroprotection
lcsh:RC346-429
Brain Ischemia
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Neuroinflammation
In vivo
medicine
Animals
Humans
lcsh:Neurology. Diseases of the nervous system
Neurons
Cell Death
Research
General Neuroscience
Alzheimer's disease
Coculture Techniques
Cell biology
030104 developmental biology
Neurology
nervous system
Microglia
medicine.symptom
Neuroscience
Alzheimer’s disease
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 17422094
- Volume :
- 14
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Neuroinflammation
- Accession number :
- edsair.doi.dedup.....70b4a3ce4c20a6e6cd06f809f1c31bf4