The neuroprotective effects of 17β-estradiol pretreatment in a model of neonatal hippocampal injury induced by trimethyltin

Elisa Marchese, Valentina Corvino, Valentina Di Maria, Alfredo Furno, Stefano Giannetti, Eleonora Cesari, Paola Lulli, Fabrizio Michetti, Maria Concetta Geloso

Research output: Contribution to journalArticle

Abstract

Hippocampal dysfunction plays a central role in neurodevelopmental disorders, resulting in severe impairment of cognitive abilities, including memory and learning. On this basis, developmental studies represent an important tool both to understanding the cellular and molecular phenomena underlying early hippocampal damage and to study possible therapeutic interventions, that may modify the progression of neuronal death. Given the modulatory role played by 17β-estradiol (E2) on hippocampal functions and its neuroprotective properties, the present study investigates the effects of pretreatment with E2 in a model of neonatal hippocampal injury obtained by trimethyltin (TMT) administration, characterized by neuronal loss in CA1 and CA3 subfields and astroglial and microglial activation. At post-natal days (P)5 and P6 animals received E2 administration (0.2 mg/kg/die i.p.) or vehicle. At P7 they received a single dose of TMT (6.5 mg/kg i.p.) and were sacrificed 72 h (P10) or 7 days after TMT treatment (P14). Our findings indicate that pretreatment with E2 exerts a protective effect against hippocampal damage induced by TMT administration early in development, reducing the extent of neuronal death in the CA1 subfield, inducing the activation of genes involved in neuroprotection, lowering the neuroinflammatory response and restoring neuropeptide Y- and parvalbumin- expression, which is impaired in the early phases of TMT-induced damage. Our data support the efficacy of estrogen-based neuroprotective approaches to counteract early occurring hippocampal damage in the developing hippocampus.

Original languageEnglish
Article number385
JournalFrontiers in Cellular Neuroscience
Volume12
DOIs
Publication statusPublished - Oct 26 2018

Keywords

  • Estrogen
  • Hippocampus
  • Neuroinflammation
  • Neuroprotection
  • Post-natal development
  • Trimethyltin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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    Marchese, E., Corvino, V., Di Maria, V., Furno, A., Giannetti, S., Cesari, E., Lulli, P., Michetti, F., & Geloso, M. C. (2018). The neuroprotective effects of 17β-estradiol pretreatment in a model of neonatal hippocampal injury induced by trimethyltin. Frontiers in Cellular Neuroscience, 12, [385]. https://doi.org/10.3389/fncel.2018.00385