Altered expression and alpha-1 adrenergic receptor mediated activity of protein kinase C in the prefrontal cortex of rats with neonatal ventral hippocampus lesions

Irina Al khairi, Moogeh Baharnoori, Aarthi Kamath, Sanjeev K. Bhardwaj, Lalit K. Srivastava

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The neonatal ventral hippocampus (nVH) lesion in rats captures many features of schizophrenia at the levels of behavior and neurobiological markers. We have previously reported enhanced expression of α-1 adrenergic receptors (AR) in the prefrontal cortex (PFC) of postpubertal nVH-lesioned rats and proposed that enhanced α-1 AR signaling might participate in some of the behavioral abnormalities observed in the nVH-lesioned rats. To assess the components of α-1 adrenergic signaling in nVH-lesiond rats, we examined prefrontal cortical expression of protein kinase C (PKC) subtypes by Western blotting and α-1 AR-stimulated PKC activity by in vitro enzyme assay in postpubertal animals. Neonatal VH-lesioned animals showed significantly increased expression of membrane-bound PKC-α and the phosphorylated form of PKC. Cytosolic PKC-bII and PKC-γ expression were found to be decreased in the PFC of lesioned animals with no change in the expression of PKC-βI either in the cytosol or membrane. PKC activity assays showed an increase in basal PKC activity in the PFC slices of nVH-lesioned animals. Stimulation of α-1 adrenergic receptor with different concentrations of the agonist phenylephrine (PE), while increasing PKC activity in the sham-lesioned animals surprisingly decreased the activity in nVHlesioned animals. Increased basal levels as well as activity of prefrontal PKC and its anomalous regulation by α-1 adrenergic receptors may participate in the cognitive and stress-induced behavioral alterations in nVH-lesioned animals.

Original languageEnglish
Pages (from-to)1051-1059
Number of pages9
JournalSynapse
Volume63
Issue number12
DOIs
Publication statusPublished - 1 Dec 2009

Keywords

  • Animal model
  • Neurodevelopment
  • Norepinephrine
  • Schizophrenia
  • Signal transudation

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