The mechanism of memory impairment induced by Aβ chronic administration involves imbalance between cytokines and neurotrophins in the rat hippocampus.
It has been demonstrated that the onset and progression of Alzheimer's 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 Aβ(25-35) for 14 days. The results showed that Aβ (25-35)-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.
Department of Biomedical Sciences, AVC, University of Prince Edward Island and Canada National Research Institute for Nutrisciences and Health, Charlottetown, PE. C1A4P3, Canada.
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D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans
D016229:Amyloid beta-Peptides; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)