This application proposes to identify which synapses are involved in phased synaptic remodeling. By quantitative ultra-structural morphometry and synapse counts, the effects of ovariectomy (low estrogen), progesterone, and ring A-reduced androgens will be studied. Freeze-fracture analysis will be used to determine whether intramembranous protein particle(IMP) deletion regularly precedes synaptic changes and whether there is a critical level of IMP density in postsynaptic membranes below which it is not possible to maintain cyclic circuitry. Neuronal proliferation and differentiation in fetal hypothalamic cell cultures will be studied utilizing cell- and molecular biology methods to probe the appearance of oncogenes and intracellular/membrane proteins.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Biochemical Endocrinology Study Section (BCE)
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Yale University
Schools of Medicine
New Haven
United States
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Naftolin, Frederick; Malaspina, Dolores (2007) Estrogen, estrogen treatment and the post-reproductive woman's brain. Maturitas 57:23-6
Naftolin, F; Horvath, T L; Balthazart, J (2001) Estrogen synthetase (aromatase) immunohistochemistry reveals concordance between avian and rodent limbic systems and hypothalami. Exp Biol Med (Maywood) 226:717-25
Keefe, D L; Watson, R; Naftolin, F (1999) Hormone replacement therapy may alleviate sleep apnea in menopausal women: a pilot study. Menopause 6:196-200
Horvath, T L; Garcia-Segura, L M; Naftolin, F (1997) Lack of gonadotropin-positive feedback in the male rat is associated with lack of estrogen-induced synaptic plasticity in the arcuate nucleus. Neuroendocrinology 65:136-40
Diano, S; Naftolin, F; Horvath, T L (1997) Gonadal steroids target AMPA glutamate receptor-containing neurons in the rat hypothalamus, septum and amygdala: a morphological and biochemical study. Endocrinology 138:778-89
Horvath, T L; Roa-Pena, L; Jakab, R L et al. (1997) Aromatase in axonal processes of early postnatal hypothalamic and limbic areas including the cingulate cortex. J Steroid Biochem Mol Biol 61:349-57
Fernandez-Galaz, M C; Morschl, E; Chowen, J A et al. (1997) Role of astroglia and insulin-like growth factor-I in gonadal hormone-dependent synaptic plasticity. Brain Res Bull 44:525-31
Parducz, A; Szilagyi, T; Hoyk, S et al. (1996) Neuroplastic changes in the hypothalamic arcuate nucleus: the estradiol effect is accompanied by increased exoendocytotic activity of neuronal membranes. Cell Mol Neurobiol 16:259-69
Garcia-Segura, L M; Chowen, J A; Duenas, M et al. (1996) Gonadal steroids and astroglial plasticity. Cell Mol Neurobiol 16:225-37
Duenas, M; Torres-Aleman, I; Naftolin, F et al. (1996) Interaction of insulin-like growth factor-I and estradiol signaling pathways on hypothalamic neuronal differentiation. Neuroscience 74:531-9

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