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Trimethyltin Modulates Reelin Expression and Endogenous Neurogenesis in the Hippocampus of Developing Rats

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Abstract

Reelin is an extracellular matrix glycoprotein involved in the modulation of synaptic plasticity and essential for the proper radial migration of cortical neurons during development and for the integration and positioning of dentate granular cell progenitors; its expression is down-regulated as brain maturation is completed. Trimethyltin (TMT) is a potent neurotoxicant which causes selective neuronal death mainly localised in the CA1-CA3/hilus hippocampal regions. In the present study we analysed the expression of reelin and the modulation of endogenous neurogenesis in the postnatal rat hippocampus during TMT-induced neurodegeneration (TMT 6 mg/kg). Our results show that TMT administration induces changes in the physiological postnatal decrease of reelin expression in the hippocampus of developing rats. In particular, quantitative analysis of reelin-positive cells evidenced, in TMT-treated animals, a persistent reelin expression in the stratum lacunosum moleculare of Cornu Ammonis and in the molecular layer of Dentate Gyrus. In addition, a significant decrease in the number of bromodeoxyuridine (BrdU)-labeled newly-generated cells was also detectable in the subgranular zone of P21 TMT-treated rats compared with P21 control animals; no differences between P28 TMT-treated rats and age-matched control group were observed. In addition the neuronal commitment of BrdU-positive cells appeared reduced in P21 TMT-treated rats compared with P28 TMT-treated animals. Thus TMT treatment, administrated during development, induces an early reduction of endogenous neurogenesis and influences the hippocampal pattern of reelin expression in a temporally and regionally specific manner, altering the physiological decrease of this protein.

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Acknowledgments

This work was supported by funds from Università Cattolica del S. Cuore to A.T. and to F.M.

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Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 000168, Rome, Italy

    Amelia Toesca, Maria Concetta Geloso, Adriana Maria Mongiovì, Alfredo Furno, Fabrizio Michetti & Valentina Corvino

  2. Institute of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 000168, Rome, Italy

    Arcangelo Schiattarella

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  1. Amelia Toesca
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  2. Maria Concetta Geloso
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  6. Fabrizio Michetti
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  7. Valentina Corvino
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Correspondence to Fabrizio Michetti or Valentina Corvino.

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Fabrizio Michetti and Valentina Corvino share the senior position.

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Toesca, A., Geloso, M.C., Mongiovì, A.M. et al. Trimethyltin Modulates Reelin Expression and Endogenous Neurogenesis in the Hippocampus of Developing Rats. Neurochem Res 41, 1559–1569 (2016). https://doi.org/10.1007/s11064-016-1869-1

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