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  • Title: Altered expression and alpha-1 adrenergic receptor mediated activity of protein kinase C in the prefrontal cortex of rats with neonatal ventral hippocampus lesions.
    Author: Al-Khairi I, Baharnoori M, Kamath A, Bhardwaj SK, Srivastava LK.
    Journal: Synapse; 2009 Dec; 63(12):1051-9. PubMed ID: 19637275.
    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 alpha-1 adrenergic receptors (AR) in the prefrontal cortex (PFC) of postpubertal nVH-lesioned rats and proposed that enhanced alpha-1 AR signaling might participate in some of the behavioral abnormalities observed in the nVH-lesioned rats. To assess the components of alpha-1 adrenergic signaling in nVH-lesion rats, we examined prefrontal cortical expression of protein kinase C (PKC) subtypes by Western blotting and alpha-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-alpha and the phosphorylated form of PKC. Cytosolic PKC-beta II and PKC-gamma expression were found to be decreased in the PFC of lesioned animals with no change in the expression of PKC-beta I 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 alpha-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 nVH-lesioned animals. Increased basal levels as well as activity of prefrontal PKC and its anomalous regulation by alpha-1 adrenergic receptors may participate in the cognitive and stress-induced behavioral alterations in nVH-lesioned animals.
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