Interactive effects of excitotoxic injury and dietary restriction on microgliosis and neurogenesis in the hippocampus of adult mice.

Responses to neuronal degeneration are complex, involving activation of microglia, astrocytes, and synaptic remodeling. It has also been suggested that neuronal injury stimulates neurogenesis, the production of new neurons from neural stem cells. Because dietary restriction (DR) can increase hippocampal neurogenesis and promotes the survival of neurons following injury, we determined the effects of DR on the responses of neural stem cells, microglia, and astrocytes in the hippocampus to seizure-induced hippocampal damage. Mice on ad libitum or DR diets were given an intrahippocampal injection of kainate, administered the DNA precursor bromodeoxyuridine (BrdU) during a 5-d period, and euthanized 1 d or 3 wk later. Although kainate greatly increased the numbers of BrdU-labeled cells, it did not enhance neurogenesis and damaged neurons were not replaced. Instead, most BrdU-labeled cells were either proliferating microglia or neural progenitor cells that subsequently died. Microgliosis was transient and was strongly correlated with the amount of damage to CA3 neurons, whereas astrocytosis was delayed and not correlated with neuronal loss. Surprisingly, neurogenesis was not increased in response to seizure-induced damage, and although DR increased basal neurogenesis, it did not promote neurogenesis following brain injury. DR significantly decreased seizure-induced microgliosis, but did not affect astrocytosis. Our findings show that DR suppresses injuryinduced microgliosis suggesting a contribution of a reduced microglial response to the neuroprotective effects of DR.