Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Major depression might originate from both environmental and genetic risk factors. The environmental chronic mild stress (CMS) model mimics some environmental factors contributing to human depression and induces anhedonia and helplessness. Mice heterozygous for the synaptic vesicle protein (SVP) vesicular glutamate transporter 1 (VGLUT1) have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour. Here, we aimed to identify, in these two experimental models, gene expression changes in the frontal cortex, common to stress and impaired glutamate function. Both VGLUT1(+/-) and CMS mice showed helpless and anhedonic-like behavior. Microarray studies in VGLUT1(+/-) mice revealed regulation of genes involved in apoptosis, neurogenesis, synaptic transmission, protein metabolic process or learning and memory. In addition, RT-PCR studies confirmed gene expression changes in several glutamate, GABA, dopamine and serotonin neurotransmitter receptors. On the other hand, CMS affected the regulation of 147 transcripts, some of them involved in response to stress and oxidoreductase activity. Interestingly, 52 genes were similarly regulated in both models. Specifically, a dowregulation in genes that promote cell proliferation (Anapc7), cell growth (CsnK1g1), cell survival (Hdac3), and inhibition of apoptosis (Dido1) was observed. Genes linked to cytoskeleton (Hspg2, Invs), psychiatric disorders (Grin1, MapK12) or an antioxidant enzyme (Gpx2) were also downregulated. Moreover, genes that inhibit the MAPK pathways (Dusp14), stimulate oxidative metabolism (Eif4a2) and enhance glutamate transmission (Rab8b) were upregulated. We suggest that these genes could form part of the altered "molecular context" underlying depressive-like behaviour in animal models. The clinical relevance of these findings is discussed.
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PMID:Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex. 2093 55

Olfactory bulbectomy (OBX) model has been proposed as a well documented model of depression. Accumulated evidences suggest that cAMP selective PDE4 enzyme plays an important role in the pathophysiology of depression disorder. Moreover, PDE4 inhibitors have shown antidepressant-like effect in behavioral despair models. However, the potential of PDE4 inhibitors to produce antidepressant-like effect in OBX model and their underlying mechanism(s) has not been adequately addressed. The present study was designed to investigate the possible antidepressant-like effects and underlying mechanism of rolipram in OBX model. The effects of rolipram were measured in a battery of behavioral paradigms, including hyperactivity in open field test (OFT), anhedonia behavior in sucrose consumption test, open arm activity in elevated plus maze test (EPM) and emotional scores in hyperemotionality test. The underlying signaling mechanisms were also investigated by measuring serum corticosterone (CORT), brain-derived neurotrophic factor (BDNF) and brain oxidant/antioxidant levels. Treatment with rolipram (0.5 and 1mg/kg, p.o., 14days) significantly improved the behavioral anomalies (decreased the hyperactivity, open arm activity and hyperemotionality scores, whereas, increased sucrose consumption). Further, rolipram significantly decreased the CORT level and increased cAMP, pCREB and BDNF levels. Additionally, rolipram reduced oxidative-nitrosative stress markers (lipid peroxidation and nitrite levels) and restored the antioxidant enzyme level, including reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), indicating attenuation of oxidative-nitrosative stress. Our results revealed that antidepressant-like effects of rolipram in OBX model may be mediated by modulating the hypothalamic-pituitary-adrenal (HPA) axis activity, increasing the cAMP signaling aspects and restoring the antioxidant mechanisms.
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PMID:Type 4 phosphodiesterase enzyme inhibitor, rolipram rescues behavioral deficits in olfactory bulbectomy models of depression: Involvement of hypothalamic-pituitary-adrenal axis, cAMP signaling aspects and antioxidant defense system. 2571 74