Behavioral and neurochemical characterization of TrkB-dependent mechanisms of agomelatine in glucocorticoid receptor-impaired mice

Boulle, Fabien; Velthuis, Hester; Koedam, K.; Steinbusch, Harry W.M.; Hove, Daniël L.A. van den; Kenis, Günter; Gabriel, C.; Mocaër, Elisabeth; Franc, Bernard; Rognan, Didier; Mongeau, Raymond; Lanfumey, Laurence

doi:10.1016/j.euroneuro.2015.11.003

Cited by 22 publications

(13 citation statements)

References 64 publications

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“…However, the fact that the interaction ratio of CSDS-exposed mice treated with agomelatine did not differ from that of vehicle-treated mice suggest that this antidepressant was ineffective to reverse a depression-related behavior in the present social avoidance test. Those results did not meet previous results since agomelatine after chronic administration at the same dose ranges has been shown to display significant efficacy in various preclinical depression-like models related to stress including the transgenic GR-i mouse3637, the corticosterone-treated mouse38, the chronic mild stress in rats39 and the prenatally stressed rat2940, but for most of them, the stress procedure was different and based on much milder stressors than those applied here. As expected from CSDS experiments, susceptible mice displayed a strong decreased in the exploration of the center of an open field on D11, indicating a clear-cut anxious-like phenotype4142.…”

Section: Discussioncontrasting

confidence: 90%

“…On D29, the effect of social defeat stress on anxiety-related behavior was still present in stressed-HEC mice, but again, agomelatine was not able to reverse this behavior. These data are not in line with previous results since agomelatine at antidepressant doses was shown to possess anxiolytic properties in naïve rats4344 and also in various rodent depression-like models373840. In particular, in the open field, a chronic agomelatine treatment was shown to reverse the anxiety-like phenotype induced by chronic corticosterone consumption in drinking water38.…”

Section: Discussioncontrasting

confidence: 66%

“…on hippocampal Bdnf gene expression both in naïve rodents26596061 and in depressive like-models2737. The particular regulation of the Bdnf IV transcript had already been proposed to be crucial in the mechanism of action of antidepressant drugs37. Interestingly, this transcript is known to selectively stimulate proximal dendrites growth in primary cultures of rat hippocampal neurons62.…”

Section: Discussionmentioning

confidence: 99%

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Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice

Martin¹,

Allaïli²,

Euvrard³

et al. 2017

Sci Rep

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Chronic stress is known to induce not only anxiety and depressive-like phenotypes in mice but also cognitive impairments, for which the action of classical antidepressant compounds remains unsatisfactory. In this context, we investigated the effects of chronic social defeat stress (CSDS) on anxiety-, social- and cognitive-related behaviors, as well as hippocampal Bdnf, synaptic plasticity markers (PSD-95, Synaptophysin, Spinophilin, Synapsin I and MAP-2), and epigenetic modifying enzymes (MYST2, HDAC2, HDAC6, MLL3, KDM5B, DNMT3B, GADD45B) gene expression in C57BL/6J mice. CSDS for 10 days provoked long-lasting anxious-like phenotype in the open field and episodic memory deficits in the novel object recognition test. While total Bdnf mRNA level was unchanged, Bdnf exon IV, MAP-2, HDAC2, HDAC6 and MLL3 gene expression was significantly decreased in the CSDS mouse hippocampus. In CSDS mice treated 3 weeks with 50 mg/kg/d agomelatine, an antidepressant with melatonergic receptor agonist and 5-HT2C receptor antagonist properties, the anxious-like phenotype was not reversed, but the treatment successfully prevented the cognitive impairments and hippocampal gene expression modifications. Altogether, these data evidenced that, in mice, agomelatine was effective in alleviating stress-induced altered cognitive functions, possibly through a mechanism involving BDNF signaling, synaptic plasticity and epigenetic remodeling.

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Section: Discussioncontrasting

confidence: 90%

Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice

Martin¹,

Allaïli²,

Euvrard³

et al. 2017

Sci Rep

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“…In addition, BDNF expression in the brain of rats was upregulated after chronic antidepressant drug exposure and ECT (Altar et al 2003; Balu et al 2008; Jacobsen and Mork 2004; Nibuya et al 1995). Interestingly, some studies have shown that antidepressant-like effects observed in mouse models of depression after chronic administration of antidepressants were reversed by TrkB antagonist injection (Boulle et al 2016; Ma et al 2016; Yasuda et al 2014) and that inhibition of TrkB signaling blocked the effects of antidepressants (Saarelainen et al 2003). Interestingly, in addition to its effects on BDNF expression, autophosphorylation of TrkB by antidepressants has also been reported by the group of Castren (Rantamaki et al 2007; Saarelainen et al 2003) suggesting that TrkB can be transactivated independently from neurotrophins, as demonstrated in the case of glucocorticoid receptors (Jeanneteau et al 2008).…”

Section: Neurotrophins and Other Growth Factorsmentioning

confidence: 99%

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

et al. 2018

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Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial effects by enhancing trophic signaling on neuronal and synaptic plasticity. However, current antidepressants still show a delayed onset of action, as well as lack of efficacy. Hence, a deeper understanding of the molecular and cellular mechanisms involved in the pathophysiology of depression, as well as in the action of antidepressants, might provide further insight to drive the development of novel fast-acting and more effective therapies. Here, we summarize the current literature on the involvement of neurotrophic factors in the pathophysiology and treatment of depression. Further, we advocate that future development of antidepressants should be based on the neurotrophin theory.

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“…GRi mice exhibited marked alterations in depressive-like and anxiety-like behaviors, together with a significant increase in fear-related behaviors. They also showed decreased cell proliferation and altered levels of neuroplastic and epigenetic markers in the hippocampus (Paizanis et al, 2010, Boulle et al, 2016. We also used mice overexpressing the human 5-hydroxytryptamine transporter (h5-HTT) (Line et al, 2011) as these animals have higher clearance of 5-HT and, theoretically, lower serotonin function.…”

Section: Introductionmentioning

confidence: 99%

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders

Matrov

Kaart

Lanfumey

et al. 2019

Behavioural Brain Research

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The psychopathology of depression is highly complex and the outcome of studies on animal models is divergent. In order to find brain regions that could be metabolically distinctively active across a variety of mouse depression models and to compare the interconnectivity of brain regions of wild-type and such genetically modified mice, histochemical mapping of oxidative metabolism was performed by the measurement of cytochrome oxidase activity. We included mice with the heterozygous knockout of the vesicular glutamate transporter (VGLUT1 −/+ ), full knockout of the cannabinoid 1 receptor (CB1 −/− ), an anti-sense knockdown of the glucocorticoid receptor (GRi) and overexpression of the human 5-hydroxytryptamine transporter (h5-HTT). Altogether 76 mouse brains were studied to measure oxidative metabolism in one hundred brain regions, and the obtained dataset was submitted to a variety of machine learning algorithms and multidimensional scaling. Overall, the top brain regions having the largest contribution to classification into depression model were the lateroanterior hypothalamic nucleus, the anterior part of the basomedial amygdaloid nucleus, claustrum, the suprachiasmatic nucleus, the ventromedial hypothalamic nucleus, and the anterior hypothalamic area. In terms of the patterns of interregional relationship between wild-type and genetically modified mice there was little overall difference, while the most deviating brain regions were cortical amygdala and ventrolateral and ventral posteromedial thalamic nuclei. The GRi mice that most clearly differed from their controls exhibited deviation of connectivity for a number of brain regions, such as ventrolateral thalamic nucleus, the intermediate part of the lateral septal nucleus, the anteriodorsal part of the medial amygdaloid nucleus, the medial division of the central amygdaloid nucleus, ventral pallidum, nucleus of the vertical limb of the diagonal band, anteroventral parts of the thalamic nucleus and parts of the bed nucleus of the stria terminalis. Conclusively, the GRi mouse model was characterized by changes in the functional connectivity of the extended amygdala and stress response circuits. Cytochrome oxidase histochemistry cortex, CA1 field CA1 of hippocampus, CA2 field CA2 of hippocampus, CA3 field CA3 of hippocampus, FrA frontal association cortex, GP globus pallidus, IL infralimbic cortex, IPR interpeduncular nucleus rostral subnucleus, Lent lateral entorhinal cortex, LHb lateral habenular nucleus, LH lateral hypothalamic area, LO lateral orbital cortex, LPAG lateral periaqueductal gray, LPO lateral preoptic area, LSI lateral septal nucleus intermediate part, LA lateroanterior hypothalamic nucleus, LC locus coeruleus, MeAD medial amygdaloid nucleus anterior dorsal, MHb medial habenular nucleus, MM medial mammillary nucleus medial part, MO medial orbital cortex, MPA medial preoptic area, MPOM medial preoptic nucleus medial part, MS medial septal nucleus, MnPO median preoptic nucleus, MnR median raphe nucleus, MDL mediodorsal thalamic nucleus lateral pa...

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Behavioral and neurochemical characterization of TrkB-dependent mechanisms of agomelatine in glucocorticoid receptor-impaired mice

Cited by 22 publications

References 64 publications

Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice

Effect of agomelatine on memory deficits and hippocampal gene expression induced by chronic social defeat stress in mice

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression

Cerebral oxidative metabolism mapping in four genetic mouse models of anxiety and mood disorders

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