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Neonatal anesthesia impairs synapsin 1 and synaptotagmin 1, two key regulators of synaptic vesicle docking and fusion.
Atluri, Navya; Ferrarese, Bianca; Osuru, Hari P; Sica, Ryan; Keller, Caroline; Zuo, Zhiyi; Lunardi, Nadia.
Afiliação
  • Atluri N; Department of Anesthesiology, University of Virginia Health System.
  • Ferrarese B; Department of Anesthesiology, University of Virginia Health System.
  • Osuru HP; Department of Anesthesiology, Universita' degli Studi di Padova, Padova, Italy.
  • Sica R; Department of Anesthesiology, University of Virginia Health System.
  • Keller C; School of Medicine.
  • Zuo Z; Undergraduate Program, University of Virginia, Charlottesville, Virginia, USA.
  • Lunardi N; Department of Anesthesiology, University of Virginia Health System.
Neuroreport ; 30(8): 544-549, 2019 05 22.
Article em En | MEDLINE | ID: mdl-30964765
Early exposure to anesthetics may interfere with synaptic development and lead to cognitive deficits. We previously demonstrated a decrease in vesicles docked at and within 100 nm from the presynaptic membrane in hippocampal nerve terminals of neonatal rats after anesthesia. Hence, we designed this study to assess the effects of neonatal anesthesia on synapsin 1 (Syn1) and synaptotagmin 1 (Syt1), two key regulators of vesicle docking and fusion. To test the link between changes in Syn1 and Syt1 and behavioral deficits observed after neonatal anesthesia, we also assessed retention memory and fear conditioning in adolescent rats after neonatal anesthesia. Pups received a combination of clinical anesthetics, then Syn1 and Syt1 mRNA and protein expression were determined at the peak (postnatal day 8, P8), part-way through (P12) and end of synaptogenesis (P24) in the CA1-subiculum by qPCR and western blotting. Anesthesia decreased Syn1 and Syt1 mRNA expression at P8 (P<0.01 and <0.001) and P12 (P=0.001 and 0.017), but not P24 (P=0.538 and 0.671), and impaired Syn1, p-Syn1, and Syt1 protein levels at P8 (P=0.038, 0.041, and 0.004, respectively), P12 (P<0.001, P=0.001, and P<0.0001), and P24 (P=0.025, 0.031, and 0.001). Anesthetic-challenged rats displayed deficient long-term retention memory (P=0.019) and hippocampus-dependent fear conditioning (P<0.001). These results suggest that anesthetics alter Syn1 and Syt1 during synapse assembly and maturation, raising the possibility that anesthetic interference with Syn1 and Syt1 could initiate changes in synaptic function that contribute to the cognitive deficits observed after neonatal anesthesia.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vesículas Sinápticas / Sinapsinas / Anestésicos Inalatórios / Sinaptotagmina I / Região CA1 Hipocampal / Isoflurano Limite: Animals Idioma: En Revista: Neuroreport Assunto da revista: NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vesículas Sinápticas / Sinapsinas / Anestésicos Inalatórios / Sinaptotagmina I / Região CA1 Hipocampal / Isoflurano Limite: Animals Idioma: En Revista: Neuroreport Assunto da revista: NEUROLOGIA Ano de publicação: 2019 Tipo de documento: Article