Learning And Running Enhance Neurogenesis In The Hippocampal Dentate Gyrus Of Adult Rats And Improve Spatial Learning Ability

Objective: (1)To investigate the effects of Y maze learning and motor-driven wheel running on neural stem cell/precursor proliferation in the hippocampal dentate gyrus of adult rats. (2)To observe the differentiation of newly generated cells by motor-driven wheel running and their effects on the performance of spatial learning.Methods: (1) Y maze learning and motor-driven wheel running were used to make the models of spatial learning and physical exercise, respectively. Intraperitoneal injection (ip) of 5-bromo-2-deoxyuridine (BrdU), the thymidine analog, that can incorporated into the DNA during the S phase of cell cycle, was applied to mark cell proliferation. Neuroepthelial stem cell protein (Nestin) expression was used to identify neuroprecursor cells. The BrdU-positive cells and Nestin-positive cells were observed as cell proliferation, which was examined by using BrdU, Nestin and avidin-biotin complex(ABC) immunocytochemical technique. (2) The ability of spatial learning and memory was evaluated by Y maze and Morris water maze learning. (3) Tubulin(Tuj-l) was used to label theimmature neuron and glial fibrillary acidic protein(GFAP) to label the astrocyte. Both of them were conducted to determine the differentiation of newly generated cells by motor-driven wheel running.Results : (1)A few BrdU-positive cells were visualized in the hippocampal dentate gyrus of adult rats. These cells were located in granular cell layer(GCL)> subgranular layer(SGL) and hilus, specially, most of which in SGL. (2)Nestin-positive cells in the hippocampal dentate gyrus of adult rats were loosely arrayed, located in the SGL and extended into the GCL. (3)Y maze learning enhanced the number of BrdU-positive cells and Nestin-positive cells in the hippocampal dentate gyrus. And there was a tight correlation between the performance of Y maze learning and the number of BrdU-labelled cells in the dentate gyrus. The better the performance they achieved, the more cell proliferation was. (4)Motor-driven wheel running also increased BrdU-positive cells and Nestin-positive cells of dentate gyrus, enhancing cell proliferation in the dentate gyrus. In addition, the effect of running on cell proliferation were intensity-dependent, and the increasing effect was more potent in light intensity group. (5)The newly generated cells by motor-driven wheel running was differentiated into neuron-like as well as astrocyte-like cells, most of which were astrocyte-like cells. (6)Motor-driven wheel running facilitated the acquisition of Y maze and Morris water maze learningtasks, and enhanced the hippocampus-depedent spatial learning ability.Conclusions: (l)Neurogenesis occured in adult rat hippocampus, located in SGL of dentate gyrus. (2)Both Y maze learning and motor-driven wheel running increased the cell proliferation in the hippocampal dentate gyrus of adult rats. (3)Motor-driven wheel running improved the performance of Y maze and Morris water maze learning, indicating that the enhancement of learning ability after motor-driven wheel running could be mediated by the cell proliferation in hippocampal dentate gyrus.