title: Expression of presynaptic markers in a neurodevelopmental animal model with relevance to schizophrenia.
abstract: Administration of N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) to rat pups at postnatal day (PND) 7, 9, and 11 [neonatal PCP (neoPCP) model] induces cognitive deficits similar to those observed in schizophrenia. Expression of presynaptic SNARE protein, synaptosomal-associated protein of 25 kDa (Snap25), has been shown to be downregulated in postmortem brains from patients with schizophrenia. The present study was designed to investigate the long-term effects of neoPCP administration on expression of presynaptic markers altered in schizophrenia. Using radioactive in-situ hybridization, the expression of Snap25 was measured in the prefrontal cortex and the hippocampal formation (CA1, CA3, CA4, and dentate gyrus) at PND 29 and 80 in neoPCP and control rats. As a secondary presynaptic marker, the expressional level of synaptophysin was also measured in the same areas. Stereological estimation of the number of neurons and volume was used to exclude potential bias in cell numbers. A significant reduction in the expression of Snap25 in the hippocampal CA4 region was observed in adult neoPCP rats (PND 80, P<0.01), but not in preadolescent rats (PND 29), indicating a late developmental manifestation of a presynaptic pathology. The number of neurons and volume of the CA4 region showed no change in PCP rats compared with the controls. Furthermore, expression of another presynaptic marker, synaptophysin, remained unaffected by the PCP treatment. These findings indicate that perinatal PCP injections induce a delayed presynaptic impact on the vesicle fusion machinery in a brain region important for cognitive processes.
authors.affiliation: aResearch Laboratory for Stereology and Neuroscience, Bispebjerg University Hospital bDepartment of Neuroscience and Pharmacology, Faculty of Health and Medical Sciences, Panum Institute, University of Copenhagen, Copenhagen cSynaptic Transmission I, H. Lundbeck A/S, Valby, Denmark.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Karlsen
authors.forename: Sanne S
authors.initials: SS
authors.lastname: Kaalund
authors.forename: Morten
authors.initials: M
authors.lastname: Møller
authors.forename: Niels
authors.initials: N
authors.lastname: Plath
authors.forename: Bente
authors.initials: B
authors.lastname: Pakkenberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity; D017403:In Situ Hybridization; D008297:Male; D010622:Phencyclidine / Q000633:toxicity; D051381:Rats; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D016708:Synaptophysin / Q000096:biosynthesis; D050825:Synaptosomal-Associated Protein 25 / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D004791:Enzyme Inhibitors; C494210:Snap25 protein, rat; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D010622:Phencyclidine