Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Perinatal administration of the N-methyl-Dd-aspartate (NMDA) receptor antagonist phencyclidine (PCP) has been reported to produce regionally selective apoptotic cell death in the frontal cortex. The development of certain behavioral abnormalities following PCP treatment suggested that extracortical regions such as the striatum also could be affected. In this study, perinatal PCP treatment caused a marked reduction in striatal, but not hippocampal, staining for polysialic acid-neural cell adhesion molecule (PSA-NCAM), an NMDA-regulated molecule important in synaptogenesis. In order to isolate striatal influences to the cortex, this investigation was continued in vitro using corticostriatal slices. For these experiments we cultured coronal corticostriatal slices from postnatal day 7 rats. After 4 days in vitro, PCP was added for 48 h and then washed out for 24 h before harvesting the tissue. Similar to what was observed in vivo, we found that PCP treatment results in a marked reduction in striatal staining for PSA-NCAM. No change was observed in the mature form of NCAM. In striatal synaptoneurosomes, immunoblot analysis confirmed that the levels of PSA-NCAM and synaptophysin, a molecule often used as a marker of synaptogenesis, were substantially down-regulated by PCP. These effects were prevented by M40403, a superoxide dismutase mimetic that also prevented the PCP-induced terminal dUTP nick-end labeling of DNA fragments that was observed selectively in the cortex. These data suggest that PCP causes cell death by apoptosis selectively in the cortex, but not in the striatum, following either in vivo treatment of perinatal rat pups or in vitro treatment of corticostriatal slices. Further, cortical apoptosis induced by PCP negatively impacts striatal synaptogenesis, a process important in normal neural development. This deficit is probably caused by a reduction in corticostriatal neurotransmission. It is possible that the dysregulation of striatal synaptogenesis contributes to the behavioral abnormalities observed following perinatal PCP administration in vivo.
 ...
PMID:Blockade of N-methyl-D-aspartate receptors by phencyclidine causes the loss of corticostriatal neurons. 1506 89

The FGL peptide is a neural cell adhesion molecule-derived fibroblast growth factor receptor agonist. FGL has both neurotrophic and memory enhancing properties. Neonatal phencyclidine (PCP) treatment on postnatal days 7, 9, and 11 has been shown to result in long-lasting behavioral abnormalities, including cognitive impairment relevant to schizophrenia. The present study investigated the effect of FGL on spatial learning and memory deficits induced by neonatal PCP treatment. Rat pups were treated with 30 mg/kg PCP on postnatal days 7, 9, and 11. Additionally, the rats were subjected to a chronic FGL treatment regimen where FGL was administered throughout development. Rats were tested as adults for spatial reference memory, reversal learning, and working memory in the Morris water maze. The PCP-treated rats demonstrated a robust impairment in working memory and reversal learning. However, the long-term memory component of the reference memory task was not affected by PCP. Chronic FGL treatment had no effect on the reversal learning impairment but ameliorated the working memory deficits almost to the levels of the control groups. In conclusion, the results suggest that the neonatal PCP treatment produced deficits in cognition relevant to schizophrenia. Moreover, working memory function was selectively protected by the neurotrophic peptide, FGL.
 ...
PMID:Effect of an NCAM mimetic peptide FGL on impairment in spatial learning and memory after neonatal phencyclidine treatment in rats. 1913 97

Evidence of structural abnormalities in the nervous system of recreational drug [e.g., phencyclidine (PCP) or ketamine] users and/or preclinical animal research models suggests interference with the activity of multiple neurotransmitters, particularly glutamate neurotransmission. The damage to the central nervous system (CNS) may include neuronal loss, synaptic changes, disturbed neural network formation and reduced projections to subcortical fields. Notably, the reduced projections may considerably compromise the establishment of the subcortical areas, such as the nucleus accumbens located in the basal forebrain. With its abundant dopaminergic innervation, the nucleus accumbens is believed to be directly associated with addictive behaviors and mental disorders. This review seeks to delineate the relationship between PCP/ketamine-induced loss of cortical neurons and the reduced level of polysialic acid neural cell adhesion molecule (PSA-NCAM) in the striatum, and the likely changes in striatal synaptogenesis during development. The basic mechanism of how PSA-NCAM cell surface expression may be regulated will also be discussed, as well as the hypothesis that PSA-NCAM activity is critical to the regulation of synaptic protein expression. Overall, the present review will address the general hypothesis that damage/interruption of cortico-striatal communication and subcortical synaptogenesis could underlie the erratic/sensitization or addictive states produced by chronic or prolonged PCP/ketamine usage.
 ...
PMID:Potential mechanisms for phencyclidine/ketamine-induced brain structural alterations and behavioral consequences. 3181 9