Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia Articles uri icon

authors

  • URIGÜEN, L.
  • GIL-PISA, I.
  • MUNARRIZ-CUEZVA, E.
  • BERROCOSO, E.
  • PASCAU GONZALEZ GARZON, JAVIER
  • SOTO MONTENEGRO, Mª LUISA
  • GUTIÉRREZ-ADÁN, A.
  • PINTADO, B.
  • MADRIGAL, J.L.M.
  • CASTRO, E.
  • SÁNCHEZ-BLÁZQUEZ, P.
  • ORTEGA, J.E.
  • GUERRERO, M.J.
  • FERRER-ALCON, M.
  • GARCÍA-SEVILLA, J.A
  • MICÓ, J.A.
  • DESCO MENENDEZ, MANUEL
  • LEZA, J.C.
  • PAZOS, A.
  • GARZON, J.
  • MEANA, J.J.

publication date

  • January 2013

issue

  • e221

volume

  • 3

international standard serial number (ISSN)

  • 2158-3188

abstract

  • Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia. The animal could provide valuable insights into phenotypic aspects of this psychiatric disorder.

keywords

  • munc18-1a; ppi; schizophrenia; snare; transporter knockout mice; voxel-based morphometry; dopamine transporter; prepulse inhibition; prefrontal cortex; receptor-binding; snare; deficits complex; pet