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P2‐094: The reduction of neurotrophin‐3 induced signal transduction by interleukin‐1β in cultured cortical neurons: A model of Alzheimer's disease
Author(s) -
Soi-Ampornkul Rungtip,
Tong Liqi,
Thangnipon Wipawan,
Cotman Carl W.,
Balazs Robert
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1140
Subject(s) - tropomyosin receptor kinase b , neurotrophin , mapk/erk pathway , biology , creb , neurite , tropomyosin receptor kinase c , microbiology and biotechnology , signal transduction , receptor , neurotrophic factors , neuroscience , endocrinology , medicine , growth factor , biochemistry , transcription factor , platelet derived growth factor receptor , gene , in vitro
The cerebral concentration of IL-1β is known to be elevated in Alzheimer’s disease. In view of critical roles played by mitogen-activated protein/kinase extracellular signal-regulated protein kinase (MAPK/ERK), phosphatidylinositol 3kinase (PI-3K) /Akt phosphorylation and the cAMP response element-binding protein (CREB) phosphorylation in neuronal plasticity, IL-1β might contribute to the decline in cognitive functions preceding the overt manifestation of pathologies in the disease. We examined the effects of IL-1β on NT-3 mediated signal transduction in neuronal cell cultures from rat cerebral cortex, which is known to play a crucial role for cell survival and differentiation of certain neuronal populations as well as in neuronal plasticity. IL-1β, at sublethal level, was shown to suppress the activation of NT-3-induced MAPK/ERK, Akt and CREB levels. This suggests that IL-1β may interfere with the functions of NT-3 early in the course of this disease. It was also shown that the interleukin-1 receptor antagonist (IL-1ra) blocks the effect of IL-1β on its receptor and also increases the MAPK/ERK, and CREB phosphorylation. We demonstrated that NT-3 protects cortical neurons against apoptosis induced by serum deprivation. Our study indicates that NT-3 is a neuroprotector which displays an anti-apoptotic effect on cultured cortical neurons. This is likely to involve the pathways related to neuronal functions, which means that NT-3 may protect against pathogenesis of Alzheimer’s disease.