ScienceAsia 32 (2006): 115-119 |doi: 10.2306/scienceasia1513-1874.2006.32.115

Impairment of Neurotrophin-3-Induced Phosphorylation of cAMP Response Element-Binding Protein Caused by Interleukin-1 in Cultured Cortical Neurons

Rungtip Soi-ampornkul,^a Liqi Tong,^b Wipawan Thangnipon,^a* Carl W. Cotman^b and Robert Balazs^b

 
ABSTRACT: Increased expression of interleukin-1 (IL-1) has been implicated as a driving force in neurodegenerative cascades that underly the formation of neuritic plaques and neurofibrillary tangles, and the accompanying neuronal cell injury and loss. In view of the critical role played by cAMP-response element-binding protein (CREB) phosphorylation in neuronal plasticity, IL-1 might contribute to the decline in cognitive functions preceding the overt manifestation of pathologies in the neurodegenerative diseases such as Alzheimer’s disease (AD). In this study we have explored the effects of IL-1 on neurotrophin-3 (NT-3) mediated signal transduction in neuronal cell cultures of the rat cerebral cortex. Pretreatments with 10 and 50 ng/ml of IL-1 significantly suppressed the effects of NT-3 by decreasing the level of phosphorylated CREB (P-CREB) to 89% and 71% (p< 0.05) of the level with NT-3 alone, respectively. This suggests that IL- 1 may interfere with the functions of NT-3 in the early course of neuronal degeneration. We found that 5 g/ml of interleukin-1 receptor antagonist (IL-1ra) blocked IL-1, with a significant increase in CREB phosphorylation when IL-1ra was added along with IL-1. Our study also indicates that NT-3 is effective in increasing the levels of P-CREB, which may play a crucial role in signal transduction processes that mediate neuronal plasticity.

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a Neuro-Behavioral Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakhon Pathom, 73170, Thailand.
b University of California Irvine, Institute for Brain Aging and Dementia, Irvine, California, 92697-4540, U.S.A.

* Corresponding author, E-mail: grwtn@mahidol.ac.th

Received 19 Nov 2004, Accepted 23 Nov 2005