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.
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.
authors.affiliation: Douglas Mental Health University Institute, Department of Psychiatry and Neurology, McGill University, Montreal, Quebec, Canada.
authors.forename: Irina
authors.initials: I
authors.lastname: Al-Khairi
authors.forename: Moogeh
authors.initials: M
authors.lastname: Baharnoori
authors.forename: Aarthi
authors.initials: A
authors.lastname: Kamath
authors.forename: Sanjeev K
authors.initials: SK
authors.lastname: Bhardwaj
authors.forename: Lalit K
authors.initials: LK
authors.lastname: Srivastava
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000293:injuries / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D007527:Isoenzymes; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011493:Protein Kinase C