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Mechanisms of monomeric C Reactive Protein inducing neurodegeneration

AuthorsGarcía-Lara, Elisa; Aguirre, S.; Clotet Perarnau, Núria; Corpas, Rubén ; Slevin, Mark; Sanfeliu, Coral
Issue Date10-Jul-2019
CitationFENS Regional Meeting (2019)
AbstractAIM: Neuroinflammation derived from ischemic damage increases the risk of both vascular dementia and Alzheimer¿s disease (AD). The monomeric C- reactive protein (mCRP) formed in the dissociation of the pentraxin CRP within the extracellular matrix of ischemic tissue, may be a causative link between stroke-associated inflammation and memory loss. We aimed to investigate the mechanism underlying neuroinflammation and loss of neuroplasticity induced by mCRP. METHODS: We used our established in vivo model of dementia by bilateral hippocampus injection of mCRP in C57BL/6j mice. Transgenic AD mice 5XFAD were used for comparison. Cell lines of microglia BV2 and HMC3 and neuroblastoma SH-SY5Y were treated with mCRP or CRP. Microglial cells were also treated with lipopolysaccharide. We assayed hippocampus tissue and cell culture extracts for gene expression and protein levels in a search of changes underlying neuroinflammation, neuroplasticity loss and neurodegeneration. RESULTS: In vivo treatment with mCRP induced long-term loss of learning and memory, analyzed up to 6 months. First molecular results revealed lower activation of signaling pathways related to plasticity early genes Arc and Egr1 in mCRP mice. Main changes in 5XFAD were related to oxidative stress and gliosis markers. A main effect on protein processing induced by mCRP was hyperphosphorylation of tau in AD-associated pathogenic residues such as Ser202 and Ser396. We are analyzing the protective effects of anti-inflammatory agents. CONCLUSIONS: Characterizing the mechanisms of mCRP-induced dementia might contribute to fight against AD incidence in the elderly.
DescriptionTrabajo presentado en el FENS Regional Meeting, celebrado en Belgrado (Sebia), del 10 al 13 de julio de 2019
Appears in Collections:(IIBB) Comunicaciones congresos
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