Bone-marrow-derived cells contribute to the recruitment of microglial cells in response to β-amyloid deposition in APP/PS1 double transgenic Alzheimer mice

Juzen-taiho-to, an Herbal Medicine, Activates and Enhances Phagocytosis in Microglia/Macrophages

“…Although 12 hrs treatment was enough to enhance the phagocytosis, no time-dependent fashion was detected. In recent studies, more attention was paid on the effect of bone marrow-derived microglia on restricting senile plaque formation (Malm et al 2005;Simard et al 2006). In this study, using M-CSF, we induced the bone marrow stem cells or myeloid progenitor cells to differentiate to macrophages, and we found that orally administrated JTT could also enhance the phagocytosis of fAβ 42 in BMM.…”

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

“…63 Many studies have provided evidence that microglial cells are attracted to amyloid deposits both in human samples and in rodent transgenic models that develop this disease. [64][65][66][67][68][69][70][71][72][73][74] It is therefore important to study the development of these deposits, as well as the effects they have on their cellular environment. The precise role of microglia in AD is still under intensive debate.…”

“…In addition, a few studies have demonstrated that an immune response in the CNS may be beneficial to the organism since it reduces the amount of amyloid deposition. 73,95 Malm et al have clearly demonstrated that LPS treatment reduces b-amyloid deposition in APP/PS1 transgenic Alzheimer mice. The notion that microglial cells are able to phagocytose amyloid deposits has been supported in previous reports.…”

Neuroprotective roles of the P2Y2 receptor

“…As described above, P2Y 2 Rs mediate the Src-dependent transactivation of the vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells that promotes upregulation of monocyte-binding proteins (e.g., VCAM-1) and a decrease in endothelial adherens junction integrity [22,89,92,101,102]. Other studies have shown that microglia are attracted to and surround Aβ plaques in both human AD brain and rodent transgenic models that develop AD-like symptoms [228][229][230][231][232][233][234][235][236][237]. Although the role of microglial cells in AD (i.e., neurotoxic vs. neuroprotective) is controversial, recent work has shown that the majority of microglia that surround amyloid plaques in an AD mouse model are derived from monocytes originating in bone marrow [233,238] and thus must pass from the bone marrow into the bloodstream through the vasculature and across the BBB to reach sites of plaque formation in the brain.…”

“…Other studies have shown that microglia are attracted to and surround Aβ plaques in both human AD brain and rodent transgenic models that develop AD-like symptoms [228][229][230][231][232][233][234][235][236][237]. Although the role of microglial cells in AD (i.e., neurotoxic vs. neuroprotective) is controversial, recent work has shown that the majority of microglia that surround amyloid plaques in an AD mouse model are derived from monocytes originating in bone marrow [233,238] and thus must pass from the bone marrow into the bloodstream through the vasculature and across the BBB to reach sites of plaque formation in the brain. Furthermore, these bone marrow-derived microglia (to a greater extent than resident microglia in the brain) were shown to eliminate Aβ deposits by phagocytosis in AD mice [238], strongly suggesting that bone marrowderived microglia serve a neuroprotective role in restricting AD progression.…”