cDNA gene expression profile of rat hippocampus after chronic treatment with antidepressant drugs

Drigues, Noam; Poltyrev, Tatyana; Bejar, Corina; Weinstock, Marta; Youdim, M.B.H.

doi:10.1007/s00702-003-0077-8

Cited by 50 publications

(29 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Not surprisingly, a significant majority of upregulated genes were associated with neurogenesis and/or synaptogenesis: these include factors known to promote the proliferation of neuronal progenitor cells (Npy, Edg3, Lgals1, Serpinf1/Pedf, Hspb1), growth factor-associated genes involved in survival and differentiation of adult neuronal cells (Bdnf, Inhba, Acvr1c, c-Ret), and downstream immediate early genes (IEGs) and transcription factors (c-fos, Sox11, Egr3, S100a6). Among the downregulated genes were Calb1, a marker of mature granule neurons, Prdm5, which has growth-suppressive (Khawaja et al, 2004) and amitriptyline, moclobemide, and clorgyline (Drigues et al, 2003). The present microarray results support the hypothesis that BDNF and other growth factors play an important role in antidepressant activity.…”

Section: Discussionsupporting

confidence: 80%

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Miller

Schultz

Gulati

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

Despite widespread use of antidepressants, the factors underlying the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of neurons in the adult hippocampus via enhanced serotonergic signaling, but it is unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neuronal effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. Furthermore, the behavioral and neuronal responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis may be a determinant of antidepressant efficacy.

show abstract

Section: Discussionsupporting

confidence: 80%

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Miller

Schultz

Gulati

et al. 2007

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…32,33 Nsf 34 and synaptotagmin 1 35,36 have both been implicated in the regulation of neurotransmitter release. Crispino et al 37 described a modulation of Syt1 mRNA levels in area CA3 of the hippocampus during the estrous cycle with highest levels occurring during diestrus, while Jenkins et al 38 showed that rats in diestrus were more vulnerable to develop LH, thus supporting our observations that lowered levels of Syt1 are accompanied by increased stress resilience.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in the hippocampus of learned helpless and nonhelpless rats

et al. 2005

View full text Add to dashboard Cite

In the learned helplessness (LH) animal model of depression, failure to attempt escape from avoidable environmental stress, LH, indicates behavioral despair, whereas nonhelpless (NH) behavior reflects behavioral resilience to the effects of environmental stress. Comparing hippocampal gene expression with large-scale oligonucleotide microarrays, we found that stress-resilient (NH) rats, although behaviorally indistinguishable from controls, showed a distinct gene expression profile compared to LH, sham stressed, and naïve control animals. Genes that were confirmed as differentially expressed in the NH group by quantitative PCR strongly correlated in their levels of expression across all four animal groups. Differential expression could not be confirmed at the protein level. We identified several shared degenerate sequence motifs in the 3 0 untranslated region (3 0 UTR) of differentially expressed genes that could be a factor in this tight correlation of expression levels among differentially expressed genes.

show abstract

“…Such approaches have been previously used to investigate the molecular alterations induced by ADs in the hippocampus and other brain regions of naive animals (Conti et al, 2007;Gaska et al, 2012;Korostynski et al, 2013;Landgrebe et al, 2002;Lee et al, 2010;Sillaber et al, 2008;Surget et al, 2009;Takahashi et al, 2006); interpretation of these studies is, however, limited by the fact that treatment of individuals who do not display signs of depressive-like behavior is not comparable to a pathological context (Cryan and Slattery, 2007). Previous comparable studies relied on measures of a single behavioral index measurement (Drigues et al, 2003;Nakatani et al, 2004), while others using multidimensional animal models of depression focused on a single class of AD (Andrus et al, 2012;Datson et al, 2012;Lisowski et al, 2013;Surget et al, 2009) or two monoaminergic ADs (Malki et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

Patrício

Mateus‐Pinheiro

Irmler

et al. 2014

Neuropsychopharmacol

View full text Add to dashboard Cite

Major depression is a highly prevalent, multidimensional disorder. Although several classes of antidepressants (ADs) are currently available, treatment efficacy is limited, and relapse rates are high; thus, there is a need to find better therapeutic strategies. Neuroplastic changes in brain regions such as the hippocampal dentate gyrus (DG) accompany depression and its amelioration with ADs. In this study, the unpredictable chronic mild stress (uCMS) rat model of depression was used to determine the molecular mediators of chronic stress and the targets of four ADs with different pharmacological profiles (fluoxetine, imipramine, tianeptine, and agomelatine) in the hippocampal DG. All ADs, except agomelatine, reversed the depression-like behavior and neuroplastic changes produced by uCMS. Chronic stress induced significant molecular changes that were generally reversed by fluoxetine, imipramine, and tianeptine. Fluoxetine primarily acted on neurons to reduce the expression of pro-inflammatory response genes and increased a set of genes involved in cell metabolism. Similarities were found between the molecular actions and targets of imipramine and tianeptine that activated pathways related to cellular protection. Agomelatine presented a unique profile, with pronounced effects on genes related to Rho-GTPase-related pathways in oligodendrocytes and neurons. These differential molecular signatures of ADs studied contribute to our understanding of the processes implicated in the onset and treatment of depression-like symptoms.

show abstract

cDNA gene expression profile of rat hippocampus after chronic treatment with antidepressant drugs

Abstract: A significant number and homology in gene expression were observed with the three antidepressants. Many of the genes were associated with neurogenesis and synaptogenesis, including synaptophysin and neogenin.

Cited by 50 publications

References 64 publications

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Genetic Regulation of Behavioral and Neuronal Responses to Fluoxetine

Gene expression profiling in the hippocampus of learned helpless and nonhelpless rats

Differential and Converging Molecular Mechanisms of Antidepressants’ Action in the Hippocampal Dentate Gyrus

Contact Info

Product

Resources

About