Ovariectomy up-regulates neuronal neurofilament light chain mRNA expression with regional and temporal specificity

Estrogens can influence the survival, plasticity and function of many adult neurons. Many of these effects, such as neurite outgrowth and increased de ndritic spine density, are mediated by changes in neuronal cytoskeletal arc hitecture. Since neurofilament proteins play a key role in the maintenance and remodeling of the neuronal cytoskeleton, we postulated that changes in neurofilament light chain mRNA may parallel some of the alterations in neur onal architecture which follow bilateral ovariectomy. We measured neurofila ment light chain mRNA levels using a ribonuclease protection assay at two t ime-points after ovariectomy in mature female rats. One week after ovariect omy, neurofilament light chain mRNA levels (corrected for glucose-6-phospha te dehydrogenase mRNA) did not differ from sham-operated animals in the fiv e brain regions examined (hypothalamus, striatum, hippocampus, frontal cort ex and occipital cortex). Four months after ovariectomy, neurofilament ligh t chain mRNA levels were similarly unchanged in the hypothalamus and striat um. In contrast, statistically significant increases in neurofilament light chain mRNA expression were observed in the three regions receiving basal f orebrain projections (hippocampus, frontal cortex and occipital cortex). rn situ hybridization demonstrated increases in neurofilament light chain mRN A expression involving subpopulations of smaller medial septal neurons. The re also appeared to be an increased number of larger septal neurons followi ng long-term ovariectomy. We propose that atrophic changes involving basal forebrain projection fiber s are followed by compensatory axonal growth by other 'intact' basal forebr ain neurons. Increased neurofilament light chain mRNA expression and somati c hypertrophy in medial septal neurons may both be reflective of the need t o sustain an axonal network which is larger and more complex. In contrast, increased neurofilament light chain mRNA expression observed in basal foreb rain targets following long-term ovariectomy may be reflective of compensat ory changes taking place in local neurons. (C) 2001 IBRO. Published by Else vier Science Ltd. All rights reserved.