title: Estrogen administration modulates hippocampal GABAergic subpopulations in the hippocampus of trimethyltin-treated rats.
abstract: Given the well-documented involvement of estrogens in the modulation of hippocampal functions in both physiological and pathological conditions, the present study investigates the effects of 17-beta estradiol (E2) administration in the rat model of hippocampal neurodegeneration induced by trimethyltin (TMT) administration (8 mg/kg), characterized by loss of pyramidal neurons in CA1, CA3/hilus hippocampal subfields, associated with astroglial and microglial activation, seizures and cognitive impairment. After TMT/saline treatment, ovariectomized animals received two doses of E2 (0.2 mg/kg intra-peritoneal) or vehicle, and were sacrificed 48 h or 7 days after TMT-treatment. Our results indicate that in TMT-treated animals E2 administration induces the early (48 h) upregulation of genes involved in neuroprotection and synaptogenesis, namely Bcl2, trkB, cadherin 2 and cyclin-dependent-kinase-5. Increased expression levels of glutamic acid decarboxylase (gad) 67, neuropeptide Y (Npy), parvalbumin, Pgc-1α and Sirtuin 1 genes, the latter involved in parvalbumin (PV) synthesis, were also evident. Unbiased stereology performed on rats sacrificed 7 days after TMT treatment showed that although E2 does not significantly influence the extent of TMT-induced neuronal death, significantly enhances the TMT-induced modulation of GABAergic interneuron population size in selected hippocampal subfields. In particular, E2 administration causes, in TMT-treated rats, a significant increase in the number of GAD67-expressing interneurons in CA1 stratum oriens, CA3 pyramidal layer, hilus and dentate gyrus, accompanied by a parallel increase in NPY-expressing cells, essentially in the same regions, and of PV-positive cells in CA1 pyramidal layer. The present results add information concerning the role of in vivo E2 administration on mechanisms involved in cellular plasticity in the adult brain.
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Corvino
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Maria
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Marchese
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Wanda
authors.initials: W
authors.lastname: Lattanzi
authors.affiliation: Institute of Histology and Embryology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Biamonte
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Michetti
authors.affiliation: Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore Rome, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Geloso
keywords: estrogen; glutamic acid decarboxylase; hippocampal neurodegeneration; neuropeptide Y (NPY); parvalbumin; trimethyltin