TY - JOUR
T1 - Reduced activation of intracellular signaling pathways in rat prefrontal cortex after chronic phencyclidine administration
AU - Molteni, Raffaella
AU - Pasini, Matteo
AU - Moraschi, Stefania
AU - Gennarelli, Massimo
AU - Drago, Filippo
AU - Racagni, Giorgio
AU - Riva, Marco A.
PY - 2008/4
Y1 - 2008/4
N2 - Evidence exists that schizophrenia is characterized by deficits in cell-cell communication and information processing. In the present study, we used the phencyclidine (PCP) animal model of schizophrenia to investigate possible defects in intracellular signaling proteins involved in neuroplasticity. Western Blot analysis has been performed to determine total and phospho-protein levels of extracellular signal-regulated kinases 1/2 (ERK1/2), type II calcium/calmodulin-dependent protein kinase (αCaMKII) and cAMP-response element binding protein (CREB) in prefrontal cortex (PFC) and hippocampus (HIP) of rat chronically treated with PCP, whereas their mRNA levels were determined by real time RT-PCR. We found reduced levels of P-ERK1/2, P-αCaMKII and P-CREB in prefrontal cortex of PCP-treated animals when compared to controls, whereas no effects were observed on total protein or mRNA levels. Conversely, no significant changes were detected on protein levels or mRNA expression in hippocampus. Given the role of ERK1/2, αCaMKII and CREB in neuroplastic mechanisms and cell communication, our data suggest that their decreased activation following chronic PCP administration can contribute to cortical defects occurring in schizophrenia, and may therefore represent potential targets for pharmacological intervention.
AB - Evidence exists that schizophrenia is characterized by deficits in cell-cell communication and information processing. In the present study, we used the phencyclidine (PCP) animal model of schizophrenia to investigate possible defects in intracellular signaling proteins involved in neuroplasticity. Western Blot analysis has been performed to determine total and phospho-protein levels of extracellular signal-regulated kinases 1/2 (ERK1/2), type II calcium/calmodulin-dependent protein kinase (αCaMKII) and cAMP-response element binding protein (CREB) in prefrontal cortex (PFC) and hippocampus (HIP) of rat chronically treated with PCP, whereas their mRNA levels were determined by real time RT-PCR. We found reduced levels of P-ERK1/2, P-αCaMKII and P-CREB in prefrontal cortex of PCP-treated animals when compared to controls, whereas no effects were observed on total protein or mRNA levels. Conversely, no significant changes were detected on protein levels or mRNA expression in hippocampus. Given the role of ERK1/2, αCaMKII and CREB in neuroplastic mechanisms and cell communication, our data suggest that their decreased activation following chronic PCP administration can contribute to cortical defects occurring in schizophrenia, and may therefore represent potential targets for pharmacological intervention.
KW - Phencyclidine
KW - Prefrontal cortex
KW - Schizophrenia
KW - Signaling
UR - http://www.scopus.com/inward/record.url?scp=42749095155&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42749095155&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2008.02.007
DO - 10.1016/j.phrs.2008.02.007
M3 - Article
C2 - 18406625
AN - SCOPUS:42749095155
VL - 57
SP - 296
EP - 302
JO - Pharmacological Research
JF - Pharmacological Research
SN - 1043-6618
IS - 4
ER -