Comprehensive expression analysis of a rat depression model

Nakatani, Noriaki; Aburatani, Hiroyuki; Nishimura, Koji; Semba, Junʼichi; Yoshikawa, Takeo

doi:10.1038/sj.tpj.6500234

Cited by 41 publications

(25 citation statements)

References 61 publications

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“…A particular hippocampal function has not yet been reported, but in a rat model of depression, NADH dehydrogenase was up-regulated in the hippocampus (32), and a role for NADH dehydrogenases has been suggested in the context of neurodegenerative disorders (33). Ndufs2 was inversely related to the adultneurogenesis phenotypes, consistent with the idea of neurogenesis being down-regulated in depression and neurodegeneration.…”

Section: Discussionsupporting

confidence: 59%

Natural variation and genetic covariance in adult hippocampal neurogenesis

Kempermann

Chesler

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

179

162

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Adult hippocampal neurogenesis is highly variable and heritable among laboratory strains of mice. Adult neurogenesis is also remarkably plastic and can be modulated by environment and activity. Here, we provide a systematic quantitative analysis of adult hippocampal neurogenesis in two large genetic reference panels of recombinant inbred strains (BXD and AXB͞BXA, n ‫؍‬ 52 strains). We combined data on variation in neurogenesis with a new transcriptome database to extract a set of 190 genes with expression patterns that are also highly variable and that covary with rates of (i) cell proliferation, (ii) cell survival, or the numbers of surviving (iii) new neurons, and (iv) astrocytes. Expression of a subset of these neurogenesis-associated transcripts was controlled in cis across the BXD set. These self-modulating genes are particularly interesting candidates to control neurogenesis. Among these were musashi (Msi1h) and prominin1͞CD133 (Prom1), both of which are linked to stem-cell maintenance and division. Twelve neurogenesis-associated transcripts had significant cis-acting quantitative trait loci, and, of these, six had plausible biological association with adult neurogenesis (Prom1, Ssbp2, Kcnq2, Ndufs2, Camk4, and Kcnj9). Only one cis-acting candidate was linked to both neurogenesis and gliogenesis, Rapgef6, a downstream target of ras signaling. The use of genetic reference panels coupled with phenotyping and global transcriptome profiling thus allowed insight into the complexity of the genetic control of adult neurogenesis.gene array ͉ hippocampus ͉ precursor ͉ quantitative trait loci ͉ stem cell N eurogenesis in adult mammals is modulated by complex interactions among genetic and environmental factors. Our goal is to use a systems genetics approach to determine how the development of new neurons and glia is modulated by gene polymorphisms, activity, and environmental stimuli. A first step toward this goal is to analyze natural variation and genetic covariance among key neurogenesis parameters such as proliferation, survival, and differentiation of new cells. We have shown that natural variation is substantial among different strains of mice (1-3). The normal range of variation often exceeds the effects of single gene mutations in engineered lines of mice.In this study, we extended this analysis of normal variation and applied a systems genetics approach to study the covariance structure of four key parameters of adult hippocampal neurogenesis across two large genetic reference populations consisting of a total of 52 recombinant inbred strains. This approach allowed us to exploit covariance of diverse traits to demonstrate biological linkage and pleiotropy (4, 5). The analysis, however, extends beyond a correlative approach. Both of the genetic reference populations used, the BXD and AXB͞BXA sets, are standard mapping panels, making it possible to search for gene loci, so-called quantitative trait loci (QTL), that produce common variation and pleiotropy among traits linked to adult hippocampal neurogenesis.A...

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Section: Discussionsupporting

confidence: 59%

Natural variation and genetic covariance in adult hippocampal neurogenesis

Kempermann

Chesler

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

179

162

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“…It is worth remembering, how recent evidence from literature is suggesting that psychiatric diseases may result from cumulative subtle changes at the expression level rather than massive effect on a large number of genes [25,27,34,59,60].…”

Section: Discussionmentioning

confidence: 98%

Behavioural and transcriptional effects of escitalopram in the chronic escape deficit model of depression

Benatti

Alboni

Blom

et al. 2014

Behavioural Brain Research

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“…Studies interrogating the effects of drugs on gene activity in selected brain areas cannot use such a strategy because the effects of a given drug and the underlying disease cannot be differentiated with certainty. Therefore, studies aiming at discovery of genes that are regulated by antidepressants mainly rely on rodent brains (e.g., Conti et al 2007;Nakatani et al 2004;Wong and Licinio 2004;Yamada et al 2005), as genetically homogenous animals can be used, and most confounding factors can be controlled.…”

Section: Introductionmentioning

confidence: 99%

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

et al. 2008

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Introduction Monoamine-based antidepressants inhibit neurotransmitter reuptake within short time. However, it commonly takes several weeks until clinical symptoms start to resolve-indicating the involvement of effects distant from reuptake inhibition. Objective To unravel other mechanisms involved in drug action, a "reverse" pharmacological approach was applied to determine antidepressant-induced alterations of hippocampal gene expression. Materials and methodsThe behavioral response to longterm paroxetine administration of male DBA/2Ola mice was assessed by the forced swim test (FST), the modified hole board (mHB), and the dark/light box. Hippocampi of test-naive mice were dissected, and changes in gene expression by paroxetine treatment were investigated by means of microarray technology. Results and discussion Robust effects of paroxetine on passive stress-coping behavior in the FST were observed. Furthermore, anxiolytic properties of long-term antidepressant treatment could be identified in DBA mice in both, the mHB and dark/light box. Analysis of microarray results revealed a list of 60 genes differentially regulated by chronic paroxetine treatment. Preproenkephalin 1 and inhibin beta-A showed the highest level of transcriptional change. Furthermore, a number of candidates involved in neuroplasticity/neurogenesis emerged (e.g., Bdnf, Gfap, Vim, Sox11, Egr1, Stat3). Seven selected candidates were confirmed by in situ hybridization. Additional immunofluorescence colocalization studies of GFAP and vimentin showed more positive cells to be detected in long-term paroxetine-treated DBA mice. Conclusion Candidate genes identified in the current study using a mouse strain validated for its responsiveness to long-term paroxetine treatment add, in our opinion, to unraveling the mechanism of action of paroxetine as a representative for SSRIs.

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Comprehensive expression analysis of a rat depression model

Cited by 41 publications

References 61 publications

Natural variation and genetic covariance in adult hippocampal neurogenesis

Natural variation and genetic covariance in adult hippocampal neurogenesis

Behavioural and transcriptional effects of escitalopram in the chronic escape deficit model of depression

Profiling of behavioral changes and hippocampal gene expression in mice chronically treated with the SSRI paroxetine

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