Over-expression of innate immune receptors during normal brain ageing

Brain ageing results in impairment of cognitive functions and is a major risk factor for several neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease. Previous studies of diseased brains have described neuroinflammatory alterations and upregulation of specific innate immune receptors, notably the toll-like receptors (TLRs) 1–9 and the lipopolysaccharide (LPS) receptor CD14. Here, we investigated whether these innate immune receptors expression is altered also during normal aging of the brain, thus in absence of any cerebral pathology. Using Real-time PCR method, we compared expression of these receptors in brains from 1-month-, 3-months- (young), 10-months- (adult), 17-months-, 28-months-old (aged) mice. Normal brain aging in mice was associated with further up-regulation of the constitutively expressed TLR3 and TLR7 transcripts and with new expression of TLR2, TLR4, TLR5, TLR6, TLR8, TLR9 and CD14. This age-related overexpression of these innate immune receptors coincidenced with the known up-regulation of conventional markers for neuroinflammation such as TNF-a, IL-1b and iNOS. The expression pattern of TLR2, TLR3 and TLR7 was confirmed by in situ hybridization and localized in the entire brain, with more intense staining of TLR3 and TLR7 observed in the cortical areas. Mononuclear phagocytes appeared to be the cellular source of TLR2 and TLR7, but not of TLR3. Identification of an age-dependent overexpression of innate immune receptors in normal brain aging may promote further understanding of the degenerative processes associated with brain aging.