Role of apolipoprotein E and estrogen in mossy fiber sprouting in hippocampal slice cultures

A role for apolipoprotein E is implicated in regeneration of synaptic circu itry after neural injury. The in vitro mouse organotypic hippocampal slice culture system shows Timm's stained mossy fiber sprouting into the dentate gyrus molecular layer in response to deafferentation of the entorhinal cort ex. We show that cultures derived from apolipoprotein E knockout mice are d efective in this sprouting response; specifically, they show no sprouting i n the: dorsal region of the dentate gyrus, yet retain sprouting in the vent ral region. Dorsal but not ventral sprouting in cultures from C57Bl/6J mice is increased 75% by treatment with 100 pM 17 beta-estradiol; this response is blocked by both progesterone and tamoxifen. These results show that neuronal sprouting is increased by estrogen in the same region where sprouting is dependent on apolipoprotein E. Sprouting may be stimulated by estrogen through its up-regulation of apolipoprotein E ex pression leading to increased recycling of membrane lipids for use by sprou ting neurons. Estrogen and apolipoprotein E may therefore interact in their modulation of both Alzheimer's disease risk and recovery from CNS injury.