A novel mechanism of dendritic spine plasticity involving estradiol induction of prostaglandin-E2.
The mechanisms establishing and maintaining dendritic spines in the mammalian CNS remain primarily unknown. We report a novel mechanism of neuronal spine plasticity in the developing preoptic area in which estradiol induces prostaglandin-E2 (PGE2) synthesis that in turn increases the density of spine-like processes. Estradiol requires PGE2 synthesis, in vivo and in vitro, and upregulates the dendritic spine protein spinophilin, an effect attenuated by antagonism of the AMPA-kainate receptor. This signaling pathway may involve cross talk between neighboring neurons and astrocytes and appears specific to the preoptic area in that hippocampal neurons responded with an increase in spinophilin to estradiol but not PGE2. Regionally specific mechanisms of estradiol-mediated synaptic plasticity allow for epigenetic control of complex sex-typic behaviors.
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D022081:Cell Surface Extensions / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000096:biosynthesis / Q000235:genetics; D012737:Sex Factors; D000099273:Neurabins
D015232:Dinoprostone; D004958:Estradiol; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D011982:Receptors, Prostaglandin; D000099273:Neurabins