Altered expression and alpha-1 adrenergic receptor mediated activity of protein kinase C in the prefrontal cortex of rats with neonatal ventral hippocampus lesions.
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.
Al-Khairi
Irina
I
Douglas Mental Health University Institute, Department of Psychiatry and Neurology, McGill University, Montreal, Quebec, Canada.
Baharnoori
Moogeh
M
Kamath
Aarthi
A
Bhardwaj
Sanjeev K
SK
Srivastava
Lalit K
LK
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*
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D007527:Isoenzymes; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011493:Protein Kinase C