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Differential expression of presynaptic genes in a rat model of postnatal hypoxia: relevance to schizophrenia.

Abstract：

:Obstetric complications play a role in the pathophysiology of schizophrenia. However, the biological consequences during neurodevelopment until adulthood are unknown. Microarrays have been used for expression profiling in four brain regions of a rat model of neonatal hypoxia as a common factor of obstetric complications. Animals were repeatedly exposed to chronic hypoxia from postnatal (PD) day 4 through day 8 and killed at the age of 150 days. Additional groups of rats were treated with clozapine from PD 120-150. Self-spotted chips containing 340 cDNAs related to the glutamate system ("glutamate chips") were used. The data show differential (up and down) regulations of numerous genes in frontal (FR), temporal (TE) and parietal cortex (PAR), and in caudate putamen (CPU), but evidently many more genes are upregulated in frontal and temporal cortex, whereas in parietal cortex the majority of genes are downregulated. Because of their primary presynaptic occurrence, five differentially expressed genes (CPX1, NPY, NRXN1, SNAP-25, and STX1A) have been selected for comparisons with clozapine-treated animals by qRT-PCR. Complexin 1 is upregulated in FR and TE cortex but unchanged in PAR by hypoxic treatment. Clozapine downregulates it in FR but upregulates it in PAR cortex. Similarly, syntaxin 1A was upregulated in FR, but downregulated in TE and unchanged in PAR cortex, whereas clozapine downregulated it in FR but upregulated it in PAR cortex. Hence, hypoxia alters gene expression regionally specific, which is in agreement with reports on differentially expressed presynaptic genes in schizophrenia. Chronic clozapine treatment may contribute to normalize synaptic connectivity.

journal_name

Eur Arch Psychiatry Clin Neurosci

journal_title

European archives of psychiatry and clinical neuroscience

authors

Sommer JU,Schmitt A,Heck M,Schaeffer EL,Fendt M,Zink M,Nieselt K,Symons S,Petroianu G,Lex A,Herrera-Marschitz M,Spanagel R,Falkai P,Gebicke-Haerter PJ

doi

10.1007/s00406-010-0159-1

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

S81-9

eissn

0940-1334

issn

1433-8491

journal_volume

260 Suppl 2

pub_type

杂志文章

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