Interleukin-1beta, neurodegeneration, and memory impairment: an insight into imbalances between pro- and anti-inflammation, and between neurotoxicity and neuroprotection

Neurodegenerative diseases have been associated with inflammatory disorders. Many studies have demonstrated that inflammation related proteins (cytokines), such as interleukin-1beta (IL-1), play an important role in the dysfunction of brain and endocrine system. For example, IL-1 can induce amyloid protein expression (a marker of AD), increase stress hormone (can damage brain cells), and reduce acetylcholine (ACh) release (related to memory). Increased IL-1 content has been found in the blood and brain of patients with Alzheimer's or Parkinson's disease. However, the mechanism by which IL-1 induces memory impairment is unclear. The present study aims at determining the relationship between inflammatory and anti-inflammatory functions, and between neurotoxicity and brain protection (neurotrophic factors) involved in memory impairment in an animal model induced by chronic IL-1 administration. In this project, several experiments will be carried out. In the first experiment, a dynamic correlation between memory impairment and changes in ACh release and stress hormone (glucocorticoids) secretion will be studied in the brain region related to memory and neurodegeneration by a unique maze-dialysis-analysis combination. In the second experiment, the concentrations of pro- and anti-inflammatory cytokines will be measured by a new protein array system. In the third experiment, the activities of some brain cells (glia) that trigger and control inflammation in the brain will be evaluated, and will be correlated with cytokine changes. In the fourth experiment, the functions of neurotrophic factors (maintain cell function and protect brain) will be studied. This series of studies will significantly advance our understanding of the role of brain inflammatory processes in neurodegeneration, the contribution of neuroinflammation to altered homeostasis in the whole organism, and the therapeutic potential of treatments with selected endogenous factors.