Cycloheximide mimics effects of oestradiol that are linked to synaptic plasticity of hypothalamic neurons

The synaptic connectivity of the rat arcuate nucleus, a hypothalamic area rich in oestradiol receptors, is rapidly affected by physiological modifications of hormonal levels. A rise of oestradiol in plasma elicits a coordinated neuronal-glial response that begins with a rapid fall in the number of small (< 10 nm) intramembrane particles and a rapid increase in the number of large (> 10 nm) intramembrane particles in neuronal membranes, followed by a modification in the branching of astrocytic processes and finally results in decreased number of axo-somatic synapses and increased glial wrapping of the neuronal somas. In the course of a series of studies aimed to test possible non-genomic effects of oestradiol on neuronal membranes we analyzed the effect of the systemic administration of the protein synthesis inhibitor cycloheximide on the ultrastructure of arcuate neurons and granule cells of the cerebellar cortex, an area of the brain with low levels of estrogen receptors. Cycloheximide resulted in a significant inhibition of protein synthesis in hypothalmus and cerebellum of ovariectomized rats. Under these circumstances, the number of small intramembrane particles was reduced in hypothalamic and cerebellar neuronal membranes while the number of large intramembrane particles showed a decrease in cerebellar membranes and a transient increase in arcuate neuronal somas. Furthermore, cycloheximide resulted in an increased glial wrapping of arcuate neuronal somas but not of cerebellar granule cells. The ensheathing of arcuate neurons by glial was associated with a 41% decrease in the number of axo-somatic synapses. These results indicate that the protein synthesis inhibitor cycloheximide may elicit the integrated neuronal-glial response that is associated with the hormonally induced remodelling of synaptic contacts on arcuate neurons.