Peripheral immune response corresponds to local immune response in Alzheimer's disease model

Background and Aim: Alzheimer's disease is the most common cause of dimentia and there is a growing concern about its prevalence. The disease is characterized by impairment of neurons and synapses ultimately leading to cognitive impairment. The formation of plaque associated with aging resulting from the precipitation and accumulation of ẞ-amyloid and the highly phosphorylated strands of "tau" in the neurons is the pathological index of the brain of Alzheimer's disease. Along with the beta-amyloid plaques, microglia cells and astrocytes are key player in the chronic inflammatory process and pathogenesis of the disease affecting T cell response bias. Indeed, these cells are activated in response to the production and failure in the clearance of ẞ- amyloid plaques cause chronic inflammation. During this chronic inflammation, astrocytes and active microglial cells produce inflammatory mediators leading to the destruction of adjacent neurons. Methods: To do so, animal model of Alzheimer's disease was induced using intra-hippocampal injection of ẞ-amyloid and Moris water maze was performed ۷ days after the disease induction. Then, the animals were sacrificed and brain, cervical lymph node and spleen were removed. Level of each marker was determined using immunohistochemistry staining. Results: Considering chronic inflammation in the brain as the involved organ and the role of the cervical lymph nodes as the secondary lymph node of the central nervous system, in this study the pattern of Th۱, Th۲, Th۱۷ and regulatory T cell responses, in the brain, cervical lymph nodes, and spleen, as the systemic secondary lymphoid organ, were determined using their associated markers including: T-bet, GATA۳, RORYt, and FoxP۳, respectively. Then, comparisons were made between animal model of Alzheimer's disease and normals. Conclusion Results revealed that levels of T-bet, RORYt, and FoxP۳ in brain, cervical lymph node, and spleen of animal model of Alzheimer's disease were significantly more than that of the normal animals. Inversely, GATA۳ level in the brain, cervical lymph node, and spleen of animal model of Alzheimer's disease were markedly decreased compared to the normal animals. In conclusion, the results of this study show that the fluctuations in the polarization of the T cell responses are not restricted to the brain as the involved loci and its draining lymphatic organ and these changes occur systemically. This is because the same changes are seen in the spleen as in the brain and cervical lymph nodes.

کلیدواژه ها:

Alzheimer ، Cervical lymph nodes ، Spleen ، Brain ، Th۱ ، Th۲ ، Th۱۷ ، T regulatory ، T- bet ، GATA۳ ، RORYt ، FoxP۳