Loss of sexual dimorphism in rat arcuate nucleus neuronal membranes with reproductive aging

Arcuate neurons of the rat hypothalamus have a sexual dimorphic membrane phenotype: quantitative analysis of freeze-fracture replicas has revealed that a population of intramembrane protein particles (IMP) of small size (less than 10 nm) is enriched in the plasma membrane of perikarya and dendritic shafts of cycling females compared to males, whereas a population of large IMPs (greater than 10 nm) is enriched in the membrane of dendritic shafts of males. This different membrane organization is associated with a sex dimorphic synaptic connectivity. To determine whether sex differences in neuronal membrane are affected by reproductive senescence, IMPs were assessed in freeze-fracture replicas of arcuate neuronal plasma membranes of male and female Sprague-Dawley rats aged 3, 15, and 18 months. Three-month-old cycling females were studied on the morning of estrus. Senescent females were in constant estrus (15 months old) or in constant diestrus (18 months old). Young females had more IMPs with diameters under 10 nm in the inner and outer leaflets of the plasma membrane of the perikarya and dendritic shafts compared to males of the same age. In addition, young males showed an increased number of large (greater than 10 nm) IMPs in the outer membrane leaflet of dendritic shafts. No sex differences were detected in the membrane of dendritic spines. In senescent females the number of small IMPs was decreased in the perikarya and dendritic shafts compared to young females while the number of large particles was increased in the outer leaflet of the membrane of dendritic shafts, reaching values similar to those observed in males. IMP counts were not modified with aging in males and in dendritic spines of females. These results indicate that reproductive aging in female rats is associated with a remodeling of neuronal plasma membranes in arcuate neurons.