Prednisolone causes anxiety- and depression-like behaviors and altered expression of apoptotic genes in mice hippocampus

Kajiyama, Yu; Iijima, Yoshimi; Chiba, Shuichi; Furuta, Miyako; Ninomiya, Midori; Izumi, Akihiro; Shibata, Shigenobu

doi:10.1016/j.pnpbp.2009.10.018

Cited by 34 publications

(17 citation statements)

References 49 publications

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“…[ 29 ] and Kajiyama et al . [ 40 ]. The EPM test was performed two days after the OFT in the corresponding week, similar to as reported by Uriarte et al .…”

Section: Methodsmentioning

confidence: 99%

Effect of Resveratrol on Behavioral Performanceof Streptozotocin-induced Diabetic Mice inAnxiety Tests

et al. 2014

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The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV) on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4 weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM). In the second week of RSV treatment, a higher grooming frequency (P<0.05) and a lower defecation and rearing frequency (P<0.05) were detected in the OFT in the RDM group compared with the DM. There was a higher grooming frequency (P<0.05) and higher percentage of entries in open arms (P<0.05) in the RDM group than in the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect observed was a higher grooming frequency in the RDM group than in the DM group (P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were observed in a short time window (2 weeks). It is suggested that RSV may help diabetic animals to adapt to new stressing and anxiety situations and thus to improve their welfare.

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“…[ 29 ] and Kajiyama et al . [ 40 ]. The EPM test was performed two days after the OFT in the corresponding week, similar to as reported by Uriarte et al .…”

Section: Methodsmentioning

confidence: 99%

Effect of Resveratrol on Behavioral Performanceof Streptozotocin-induced Diabetic Mice inAnxiety Tests

et al. 2014

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“…Repeated intra-hippocampal administration of prednisolone (a commonly prescribed glucocorticoid) increased anxiety and depression-like behavior in mice, and altered expression of genes associated with cell death and inflammation (Kajiyama et al, 2010). Imaging studies show that hippocampal volumes are reduced in some patients with MDD (Bremner et al, 2000; MacQueen et al, 2003; Sheline et al, 1996), possibly due to reduced neuropil sizes (Rosoklija et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression

Wilhelm¹,

Choi²,

Huckans³

et al. 2013

Pharmacology Biochemistry and Behavior

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Major depression is a complex multi-factorial disorder with a lifetime diagnosis of nearly 1 out of 6. We used the Flinders Sensitive Line (FSL) of rats, a model of depression, and the parent Sprague–Dawley (SD) rats to identify genes, gene ontology categories and pathways associated with depression. Depression-like behavior was verified in the FSL line by forced swim testing, with FSL animals exhibiting greater immobility compared to SD rats. RNA samples from the hippocampus were isolated from a group of experimentally naïve FSL and SD rats for microarray analysis. Microarray analysis yielded a total of 361 genes that were differentially regulated between FSL and SD rats, with catechol-O-methyltransferase (COMT) being the most up-regulated. The genes that were differentially regulated between FSL and SD rats were subjected to bioinformatic analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID), which yielded several gene ontology categories that were overrepresented. Subsequent pathway analysis indicated dysregulation of the adipocytokine signaling pathway. To test the translational impact of this pathway, metabolic factors and psychiatric symptoms were evaluated in a sample of human research participants. Results from our human subjects indicated that anxiety and a subset of depressive symptoms were correlated with adiponectin levels (but not leptin levels). Our results and those of others suggest that disruption of the adipocytokine signaling pathway may be a critical component of the depressive-like behaviors observed in the FSL rats and may also be an important indicator of depressive and anxiety symptoms in humans.

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“…Microarrays or other expression profiling methods yield sets of differentially expressed genes that can be used to interrogate pathway databases and identify altered processes/pathways (36–40). Profiling techniques have been applied previously to analyze effects of stress or short-term exposure to GCs on gene expression in rodent hippocampal formation (41–47), but there have been no such studies on long-term exposure to normal-range levels of corticosterone (CORT), the naturally occurring GC in rodents. Consequently, neither the deleterious nor the adaptive processes mediated by chronic brain exposure to natural GCs are well understood.…”

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confidence: 99%

Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

et al. 2013

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Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the long-standing hypothesis that chronic GC exposure promotes brain aging/Alzheimer disease. Here, we adrenalectomized male F344 rats at 15 months of age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid receptor–activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between intermediate and low CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT–up-regulated genes included learning/plasticity, differentiation, glucose metabolism, and cholesterol biosynthesis, whereas processes overrepresented by CORT–down-regulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC transcriptome with a previously defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same direction, the majority were shifted in opposite directions by CORT and aging (eg, glial inflammatory genes down-regulated by CORT are up-regulated with aging). These results contradict the hypothesis that GCs simply promote brain aging and also suggest that the opposite direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways, whereas GC overstimulation develops in others, together generating much of the brain aging phenotype.

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Prednisolone causes anxiety- and depression-like behaviors and altered expression of apoptotic genes in mice hippocampus

Cited by 34 publications

References 49 publications

Effect of Resveratrol on Behavioral Performanceof Streptozotocin-induced Diabetic Mice inAnxiety Tests

Effect of Resveratrol on Behavioral Performanceof Streptozotocin-induced Diabetic Mice inAnxiety Tests

Adipocytokine signaling is altered in flinders sensitive line rats, and adiponectin correlates in humans with some symptoms of depression

Glucocorticoid-Dependent Hippocampal Transcriptome in Male Rats: Pathway-Specific Alterations With Aging

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