Pii: S0306-4522(01)00010-0

ÐEstrogens can in ̄uence the survival, plasticity and function of many adult neurons. Many of these effects, such as neurite outgrowth and increased dendritic spine density, are mediated by changes in neuronal cytoskeletal architecture. Since neuro®lament proteins play a key role in the maintenance and remodeling of the neuronal cytoskeleton, we postulated that changes in neuro®lament light chain mRNA may parallel some of the alterations in neuronal architecture which follow bilateral ovariectomy. We measured neuro®lament light chain mRNA levels using a ribonuclease protection assay at two time-points after ovariectomy in mature female rats. One week after ovariectomy, neuro®lament light chain mRNA levels (corrected for glucose-6-phosphate dehydrogenase mRNA) did not differ from sham-operated animals in the ®ve brain regions examined (hypothalamus, striatum, hippocampus, frontal cortex and occipital cortex). Four months after ovariectomy, neuro®lament light chain mRNA levels were similarly unchanged in the hypothalamus and striatum. In contrast, statistically signi®cant increases in neuro®lament light chain mRNA expression were observed in the three regions receiving basal forebrain projections (hippocampus, frontal cortex and occipital cortex). In situ hybridization demonstrated increases in neuro®lament light chain mRNA expression involving subpopulations of smaller medial septal neurons. There also appeared to be an increased number of larger septal neurons following long-term ovariectomy. We propose that atrophic changes involving basal forebrain projection ®bers are followed by compensatory axonal growth by other `intact' basal forebrain neurons. Increased neuro®lament light chain mRNA expression and somatic hypertrophy in medial septal neurons may both be re ̄ective of the need to sustain an axonal network which is larger and more complex. In contrast, increased neuro®lament light chain mRNA expression observed in basal forebrain targets following long-term ovariectomy may be re ̄ective of compensatory changes taking place in local neurons. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.