Selective Loss of Brain-Derived Neurotrophic Factor in the Dentate Gyrus Attenuates Antidepressant Efficacy

Adachi, Megumi; Barrot, Michel; Autry, Anita E.; Theobald, David E. H.; Monteggia, Lisa M.

doi:10.1016/j.biopsych.2007.09.019

Cited by 331 publications

(250 citation statements)

References 47 publications

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“…Moreover, a decrease in the BDNF mature protein has been reported in the ventral hippocampus and frontal cortex of rats with a genetic deletion of the serotonin transporter (Calabrese et al., 2013). A selective deletion of the BDNF‐encoding gene within the mouse dentate gyrus also results in a reduction in antidepressant efficacy (Adachi, Barrot, Autry, Theobald, & Monteggia, 2008) and, conversely, the infusion of BDNF into the lateral cerebral ventricle (Hoshaw, Malberg, & Lucki, 2005) or the dorsal hippocampus (Shirayama et al., 2002) elicits antidepressant effects in behavioral models of depression. There is also growing evidence that antidepressant treatments may exert some of their therapeutic effects by increasing BDNF expression levels and affecting BDNF transcription in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, it has been shown that different antidepressant treatments, such as physical activity (Baj et al., 2012; Kozisek et al., 2008), the electroconvulsive treatment, and several antidepressant medications (Adachi et al., 2008; Alboni et al., 2010; Baj et al., 2012; Elfving et al., 2010; Kozisek et al., 2008; Marmigère, Givalois, Rage, Arancibia, & Tapia‐Arancibia, 2003) modulate differently the expression of BDNF in specific hippocampal subfields. Therefore, in the present study we evaluated the basal expression of BDNF and trkB in different subregions of the hippocampus of the Roman rat lines.…”

Section: Discussionmentioning

confidence: 99%

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Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

et al. 2017

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IntroductionThe selective breeding of Roman High‐ (RHA) and Low‐Avoidance (RLA) rats for, respectively, rapid versus poor acquisition of the active avoidance response has generated two distinct phenotypes differing in many behavioral traits, including coping strategies to aversive conditions. Thus, RLA rats are considered as a genetic model of vulnerability to stress‐induced depression whereas RHA rats are a model of resilience to that trait. Besides the monoamine hypothesis of depression, there is evidence that alterations in neuronal plasticity in the hippocampus and other brain areas are critically involved in the pathophysiology of mood disorders.Materials and MethodsWestern blot (WB) and immunohistochemistry were used to investigate the basal immunochemical occurrence of brain‐derived neurotrophic factor (BDNF) and its high‐affinity tyrosine‐kinase receptor trkB in the dorsal and ventral hippocampus of adult RHA and RLA rats.Results WB analysis indicated that the optical density of BDNF‐ and trkB‐positive bands in the dorsal hippocampus is, respectively, 48% and 25% lower in RLA versus RHA rats. Densitometric analysis of BDNF‐ and trkB‐like immunoreactivity (LI) in brain sections showed that BDNF‐LI is 24% to 34% lower in the different sectors of the Ammon's horn of RLA versus RHA rats, whereas line‐related differences are observed in the dentate gyrus (DG) only in the ventral hippocampus. As for trkB‐LI, significant differences are observed only in the dorsal hippocampus, where density is 23% lower in the DG of RLA versus RHA rats, while no differences across lines occur in the Ammon's horn.ConclusionThese findings support the hypothesis that a reduced BDNF/trkB signaling in the hippocampus of RLA versus RHA rats may contribute to their more pronounced vulnerability to stress‐induced depression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

et al. 2017

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“…The mechanism that links the serotonin reuptake inhibition to the D 1 -like receptor-dependent synaptic modulation is unknown. Brain-derived neurotrophic factor (BDNF) has been implicated in antidepressant action (Adachi et al, 2008;Malberg and Blendy, 2005). Chronic fluoxetine can increase both mRNA and mature protein levels of BDNF in the hippocampus (Musazzi et al, 2009), and BDNF has been shown to greatly increase the expression of D 1 receptor mRNA in the catecholaminergic CAD cell line (Do et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…However, cellular mechanisms underlying both therapeutic and adverse effects of SSRIs have not been fully understood. The dentate gyrus of the hippocampus has been implicated in behavioral effects of SSRIs and other antidepressant drugs in experimental animals (Adachi et al, 2008;Kobayashi et al, 2011a;Miyamoto et al, 2011;Sahay and Hen, 2007;Santarelli et al, 2003). We have recently shown that the SSRI fluoxetine greatly changes serotonergic modulation at the synapse between the mossy fiber, the sole output of the dentate granule cell, and CA3 pyramidal cells .…”

Section: Introductionmentioning

confidence: 99%

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

Kobayashi

Haneda

Higuchi³

et al. 2012

Neuropsychopharmacol

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The dentate gyrus of the hippocampus has been implicated in mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). We have recently demonstrated that the SSRI fluoxetine can reverse the state of maturation of the adult dentate granule cells and enhances serotonin 5-HT 4 receptor-mediated synaptic potentiation at the synapses formed by their mossy fiber axons. Here, we show that fluoxetine can induce long-lasting enhancement of dopaminergic modulation at the mossy fiber synapse. Synaptic responses arising from the mossy fiber-CA3 pyramidal cell synapse were recorded using acute mouse hippocampal slices. Dopamine potentiates mossy fiber synaptic transmission by activating D 1 -like receptors. Chronic fluoxetine treatment induced a prominent increase in the magnitude of dopamine-induced synaptic potentiation, and this effect was maintained at least up to 1 month after withdrawal of fluoxetine. Quantitative autoradiography revealed that binding of the D 1 -like receptor ligand [ 3 H]SCH23390 was selectively increased in the dentate gyrus and along the mossy fiber in fluoxetine-treated mice. However, binding of the 5-HT 4 receptor ligand [ 3 H]GR113808 was not significantly changed. These results suggest that chronic fluoxetine enhanced the dopaminergic modulation at least in part by upregulating expression of D 1 -like receptors, while the enhanced serotonergic modulation may be mediated by modifications of downstream signaling pathways. These enhanced monoaminergic modulations would greatly increase excitatory drive to the hippocampal circuit through the dentate gyrus. The highly localized upregulation of D 1 -like receptors further supports the importance of the dentate gyrus in the mechanism of action of SSRIs.

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“…To this end, converging lines of evidence have implicated neurotrophic factors, most notably brain-derived neurotrophic factor (BDNF), as a putative mediator of antidepressant responses, along with the MEK-ERK (mitogen-activated protein kinase kinase and its target extraceullular signal-regulated protein kinase) signaling pathway (10)(11)(12)(13). Several studies have also suggested the involvement of other growth factors, such as IGF-1 (insulin-like growth factor-1), VEGF (vascular endothelial growth factor), and FGF2 (fibroblast growth factor 2), as important mediators of antidepressant responses (14).…”

Section: Signaling Pathways Implicated In Antidepressant Responsesmentioning

confidence: 99%

VGF, a New Player in Antidepressant Action?

Malberg

Monteggia

2008

Sci. Signal.

Self Cite

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Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepressant treatments, is important for the development of more potent and specific treatments of depression. There is growing evidence that growth factors may be important mediators of antidepressant responses. Now, VGF (not an acronym), a neuropeptide that has previously been shown to be involved in maintaining organismal energy balance, as well as in mediating hippocampal synaptic plasticity, may be involved in mediating antidepressant responses. These studies use in vivo approaches to link VGF to the antidepressant-like behavioral effects produced by antidepressant drugs and exercise.

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Selective Loss of Brain-Derived Neurotrophic Factor in the Dentate Gyrus Attenuates Antidepressant Efficacy

Abstract: These data suggest that the loss of hippocampal BDNF per se is not sufficient to mediate depression-like behavior. However, these results support the view that BDNF in the DG might be essential in mediating the therapeutic effect of antidepressants.

Cited by 331 publications

References 47 publications

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

Expression of BDNF and trkB in the hippocampus of a rat genetic model of vulnerability (Roman low‐avoidance) and resistance (Roman high‐avoidance) to stress‐induced depression

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

VGF, a New Player in Antidepressant Action?

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