The Mechanism of Memory Impairment Induced by Aβ Chronic Administration Involves Imbalance between Cytokines and Neurotrophins in the Rat Hippocampus

Author(s): C. Ji, C. Song, P. Zuo.

Journal Name: Current Alzheimer Research

Volume 8 , Issue 4 , 2011

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Abstract:

It has been demonstrated that the onset and progression of Alzheimers disease (AD) are associated with inflammatory disorders in the brain. Although the interactions of inflammatory cytokines with neurotrophins have been reported in vitro, the balance change between inflammatory cytokines and neurotrophic factors (NTFs), such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF), due to amyloid β (Aβ) chronic administration in vivo is still unclear. The hypothesis of the present study was that the accumulation of Aβ activated glial cells to produce inflammatory mediators and NTFs to maintain the neurons survival, however the failure of crosstalk between NTFs and inflammatory cytokines might occur in the brain and the NTFs expressions would decrease after Aβ chronic treatment, which, therefore, would contribute to the neuronal death and memory impairments. Thus, the present study measured the learning and memory behavior, glial cells activities, cytokines (IL-1α, IL-1β and TNF-α) concentrations and NTFs (NGF, BDNF and GDNF) gene and protein levels in rats after i.c.v injection of Aβ25-35 for 14 days. The results showed that Aβ25-35-treated animals exhibited failure of balance between inflammatory cytokines and NTFs system (increased cytokines levels, decreased NGF protein expression and reduced NTFs gene transcriptions), which might contribute to the cognitive impairments. The findings from this study provide valuable evidence that correct regulation of the crosstalk between inflammatory cytokines and NTFs could be a direction for AD therapy in the future.

Keywords: Alzheimer's disease (AD), neurotrophic factors (NTFs), inflammatory cytokines, microglia, astrocytes, amyloid beta, amyloid plaques, antigen, alpha, interleukin, neuron, proliferation, 3 cytokines

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Article Details

VOLUME: 8
ISSUE: 4
Year: 2011
Page: [410 - 420]
Pages: 11
DOI: 10.2174/156720511795745366
Price: $58

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