Effects of minocycline on spatial learning, hippocampal neurogenesis and microglia in aged and adult mice

Age-related priming of microglia and release of inflammatory cytokines, such as interleukin-1β (IL-1β) and interleuekin-6 (IL-6) have been associated with deficits in cognitive function. The present study assessed whether treatment with minocycline could improve spatial cognition in aged mice, and whether these improvements in behavior were associated with reduced microglia activation and an enhancement in hippocampal neurogenesis. Adult (3 months) and aged (22 months) male BALB/c mice received minocycline in their drinking water or control mice received distilled water for 20 days. Mice received BrdU to label dividing cells on days 8–17. Spatial learning was measured using the water maze. Immunohistochemistry was conducted to measure number of BrdU positive neurons and number and size of microglia by detection of Iba-1 in the dentate gyrus molecular layer. Further, hippocampal samples were collected to measure changes in IL-1β, IL-6, and CD74 expression. The data show that aged mice have increased hippocampal expression of IL-1β, IL-6, and CD74 relative to adults. Minocycline treatment significantly improved acquisition of the water maze in aged mice but not adults. Minocycline reduced the average size of Iba-1 positive cells and total Iba-1 counts, but did not affect hippocampal cytokine gene expression. Minocycline increased neurogenesis in adults but not aged mice. Collectively, the data indicate that treatment with minocycline may recover some aspects of cognitive decline associated with aging, but the effect appears to be unrelated to adult hippocampal neurogenesis.

► Minocycline attenuates age-related spatial learning deficits.
► Treatment with minocycline reduces the size of Iba-1 positive cells.
► Minocycline increases neuronal differentiation of new granular cells in adults.