research centers on estrogens as neurohormones and inducers of synaptic connections and synaptic plasticity
Photo taken on Nov.11,2002 by Terry Dagradi, Med Media Group	Fredrick Naftolin, M.D., Ph.D. Director, Center for Research in Reproductive Biology Head, Reproductive Neuroscience Unit Professor Ob/Gyn, Professor Molecular Cell & Developmental Biology Email: frederick.naftolin@yale.edu Room: FMB 331 Phone: (203) 785-4003

We study the action of estrogen on the brain. Estrogen is critical for development of embryonic/fetal hypo-thalamic neurons and glia, as well as for the maintenance of synaptic connections that control the secretion of GNRH/-gonadotrophin. We use electron microscopy, immuno-histochemistry and molecular biology techniques.

Presently we are involved in defining estrogen-induced synaptic plasticity in the monkey hypothalamus. We identify the cells that are involved through immuno-histochemistry and perform quantitative

synaptology. Our work has led to the documentation of estrogen-induced synaptic development during embryonic-/fetal life, a number of intracellular and cell membrane changes that support these synaptic developments and estrogen-induced synaptic plasticity during adult life. Our studies also include the effects of estrogen on other areas of the brain, including the hippocampus.

We also study the mechanisms by which estrogen induces synaptic changes.

We have focused on the polysialated neural cell adhesion molecule, which passes from being a cytoplasmic protein to the glycocalyx where its polyglycosylation affects interactions with adjacent neurons and glia, and the process of estrogen formation via the enzyme estrogen synthetase in the brain. We employ both in vitro and in vivo methodologies to study effects of estrogen on neurons. Some of the neurons we study are immortalized hypothalamic neurons.

These studies are concordant with our clinical interest in the menopause. In that regard, we examine the effects of various estrogens, including plant estrogens (phytoestrogens) and non-steroidal estrogen agonist-antagonists on the brain in rodents and primates.

Selected Publications

Naftolin F, Leranth C, Garcia-Segura LM. Ultrastructural changes in hypothalamic cells during estrogen-induced gonadotrophin feedback. Neuroprotocols: A comparison to methods in Neurosciences. Academic Press, Inc., San Diego, CA, 1:16-26, 1992.

Garcia-Segura LM, Chowen JA, Parducz A and Naftolin F. Gonadal Hormones as Promoters of Structural Synaptic Plasticity: Cellular Mechanisms. Prog in Neurobiol., 44:279-307, 1994.

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