Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior

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  • Betina Elfving
  • Heidi Kaastrup Müller
  • Ignasi Oliveras, Universidad Autonoma de Barcelona
  • ,
  • Tina Becher Østerbøg, Frederiksberg Hospital
  • ,
  • Cristobal Rio-Alamos, Universidad Autonoma de Barcelona, Universidad Austral de Chile
  • ,
  • Ana Sanchez-Gonzalez, Universidad Autonoma de Barcelona
  • ,
  • Adolf Tobeña, Universidad Autonoma de Barcelona
  • ,
  • Alberto Fernandez-Teruel, Universidad Autonoma de Barcelona
  • ,
  • Susana Aznar, Frederiksberg Hospital

Schizophrenia is considered a neurodevelopmental disorder. Recent reports relate synaptic alterations with disease etiology. The inbred Roman High- (RHA-I) and Low- (RLA-I) Avoidance rat strains are a congenital neurobehavioral model, with the RHA-I displaying schizophrenia-related behaviors and serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptor alterations in the prefrontal cortex (PFC). We performed a comprehensive characterization of the RHA-I/RLA-I rats by real-time qPCR and Western blotting for 5-HT1A, 5-HT2A, mGlu2, dopamine 1 and dopamine 2 receptors (DRD1 and DRD2), AMPA receptor subunits Gria1, Gria2 and NMDA receptor subunits Grin1, Grin2a and Grin2b, as well as pre- and post-synaptic components in PFC and hippocampus (HIP). Besides corroborating decreased mGlu2 (Grm2) expression, we found increased mRNA levels for Snap25, Synaptophysin (Syp), Homer1 and Neuregulin-1 (Nrg1) in the PFC of the RHA-I and decreased expression of Vamp1, and Snapin in the HIP. We also showed alterations in Vamp1, Grin2b, Syp, Snap25 and Nrg1 at protein levels. mRNA levels of Brain Derived Neurotrophic Factor (BDNF) were increased in the PFC of the RHA-I rats, with no differences in the HIP, while BDNF protein levels were decreased in PFC and increased in HIP. To investigate the temporal dynamics of these synaptic markers during neurodevelopment, we made use of the open source BrainCloud™ dataset, and found that SYP, GRIN2B, NRG1, HOMER1, DRD1 and BDNF expression is upregulated in PFC during childhood and adolescence, suggesting a more immature neurobiological endophenotype in the RHA-I strain.

Original languageEnglish
Article number109669
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume95
ISSN0278-5846
DOIs
Publication statusE-pub ahead of print - Jun 2019

    Research areas

  • Behavioral traits, Congenital animal model, Gene expression, Schizophrenia, Synaptic markers

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