T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer's disease mice

Alzheimer＇s disease is closely associated with disorders of neurogenesis in the brain, and growing evidence supports the involvement of immunological mechanisms in the development of the disease. However, at present, the role of T cells in neuronal regeneration in the brain is unknown. We injected amyloid-beta 1-42 peptide into the hippocampus of six BALB/c wild-type mice and six BALB/c-nude mice with T-cell immunodeficiency to establish an animal model of Alzhei- mer＇s disease. A further six mice of each genotype were injected with same volume of normal saline. Immunohistochemistry revealed that the number of regenerated neural progenitor cells in the hippocampus of BALB/c wild-type mice was significantly higher than that in BALB/c-nude mice. Quantitative fluorescence PCR assay showed that the expression levels of peripheral T cell-associated cytokines （interleukin-2, interferon-y） and hippocampal microglia-related cyto- kines （interleukin-113, tumor necrosis factor-a） correlated with the number of regenerated neural progenitor cells in the hippocampus. These results indicate that T cells promote hippocampal neurogenesis in Alzheimer＇s disease and T-cell immunodeficiency restricts neuronal regeneration in the hippocampus. The mechanism underlying the promotion of neuronal regeneration by T cells is mediated by an increased expression of peripheral T cells and central microglial cytokines in Alzheimer＇s disease mice. Our findings provide an experimental basis for understanding the role of T cells in Alzheimer＇s disease.

Selective loss of basal forebrain cholinergic neurons in APP_(770) transgenic mice

To determine whether cholinergic neurons in the basal nucleus magnocellularis (NBM) and the medial septum are affected in transgenic mice overexpressing human amyloid precursor protein 770 (APP 770 ) Methods Eight age groups, from 3 months old to 10 months old, of either heterozygous transgenic or non transgenic mice were used for choline acetyltransferase (ChAT) staining using immunohistochemistry The number of ChAT positive neurons was counted on the MCID Image Analysis System Neurons in the cerebral cortex and area CA1 of hippocampus were also stained with cresyl violet and counted using optical dissector technique Results There is no change in the number of forebrain cholinergic neurons in the transgenic mice up to 9 months of age A loss of these cholinergic neurons starts in 9 months old transgenic mice, with a further decrease in the number of NBM and medial septum neurons in 10 month old transgenic mice On the other hand, the number of neurons in the cerebral cortex and hippocampal area CA1 remained unchanged Conclusion These results demonstrate a selective loss of basal forebrain cholinergic neurons in APP 770 transgenic mice