Up-regulation of TREM2 accelerates the reduction of amyloid deposits and promotes neuronal regeneration in the hippocampus of amyloid beta1-42 injected mice.

Alzheimer's disease (AD) is characterized by a robust inflammatory response elicited by the accumulation and subsequently deposition of amyloid beta (Aβ) within the brain. The immune cells of brain migrate to and invest their processes within Aβ plaques and clear plaques from the brain. Previous studies have shown that treatment of myeloid cell with nuclear factor inhibitor increases expression of phagocytesis-related genes, such as triggering receptor expressed on myeloid cells 2 (TREM2). In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation as well as inflammatory response in vitro. The purpose of this study was to further investigate microglial proliferation, phagocytosis and the expression of brain derived neurotrophic factor (BDNF) induced by up-regulation of TREM2 in Aβ1-42 injected mice. We first singly injected Aβ1-42 into the hippocampus of mice to build the model of AD-like symptoms. Subsequently, ammonium pyrrolidinedithiocarbamate (PDTC) was injected into the lateral ventricle of mice. Various immunohistochemical techniques and Western blot analyses were applied to examine expressions of TREM2, microglia, Aβ, Neuronal migration protein doublecortin (DCX) and BDNF in the hippocampus of mice. In the present study, we found the plaques-associated microglia lowly expressed TREM2 and BDNF in Aβ1-42 intra-hippocampal injected mice. Treatment of the models with a nuclear factor inhibitor, PDTC, further induced the expression of TREM2 and enhanced microglial phagocytosis, coincident with the rapid reduction in plaque burden. The expression of BDNF was up-regulated and the expression of DCX was partly restored. This means that up-regulation of TREM2 might induce the microglia to express the BDNF. These findings further indicate that the level of TREM2 may affect the microglia response to pathological process induced by Aβ.