Different modes of hippocampal plasticity in response to estrogen in youngand aged female rats

Estrogen regulates hippocampal dendritic: spine density and synapse number in an N-methyl-D-aspartate (NMDA) receptor-dependent manner, and these effe cts may be of particular importance in the context of age-related changes i n endocrine status. We investigated estrogen's effects on axospinous synaps e density and the synaptic distribution of the NMDA receptor subunit, NR1, within the context of aging. Although estrogen induced an increase in axosp inous synapse density in young animals, it did not alter the synaptic repre sentation of NR1, in that the amount of NR1 per synapse was equivalent acro ss groups. Estrogen replacement in aged female rats failed to increase axos pinous synapse density; however, estrogen up-regulated synaptic NR1 compare d with aged animals with no estrogen. Therefore, the young and aged hippoca mpi react differently to estrogen replacement, with the aged animals unable to mount a plasticity response generating additional synapses, yet respons ive to estrogen with respect to additional NMDA receptor content per synaps e. These findings have important implications for estrogen replacement ther apy in the context of aging.