WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway

Jiang, Bo; Huang, Chao; Zhu, Qing; Tong, Lijuan; Zhang, Wei

doi:10.1007/s00213-014-3802-0

Cited by 45 publications

(53 citation statements)

References 54 publications

(59 reference statements)

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“…In our conditions, CSDS failed to induce any modification in total Bdnf gene expression. This does not meet previous results that demonstrated a clear downregulation of total Bdnf gene in the hippocampus of social defeated mice, at both short and long term4754555657, although one study reported no change in the same conditions58. While Bdnf exon VI mRNA gene expression was also unchanged, Bdnf exon IV mRNA was significantly downregulated in CSDS stressed mice.…”

Section: Discussioncontrasting

confidence: 99%

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: 99%

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 this experiment, the ICR mice were given the choice to drink from two bottles in individual cages, one with 1% sucrose solution and the other with water [26]. All the ICR mice were acclimatized for 2 days to two-bottle choice conditions, and the position of two bottles was changed every 6 h to prevent possible effects of side preference in drinking behavior.…”

Section: Sucrose Preference Experimentsmentioning

confidence: 99%

“…For induction of CRS, mice were restrained for 6 h/day up to 28 consecutive days in well-ventilated 50-ml polystyrene tubes. The CSDS was performed daily for 20 days according to our previous studies [26]. In this experiment, the CD1 retired breeders were used as the aggressors.…”

Section: Preparation Of Cus Crs and Csds Modelsmentioning

confidence: 99%

Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses

et al. 2017

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Recently, the loss and dystrophy of hippocampal microglia induced by chronic unpredictable stress (CUS) has been reported to mediate the development of major depression in mice whose microglial cells were labeled with enhanced green fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this happens in endogenous microglia with no genetic intervention remains unclear. Here, we addressed this issue in mice treated with different types of chronic stresses, including the CUS, chronic restraint stress (CRS) and chronic social defeat stress (CSDS). Results showed that the cellular numbers, process lengths, soma areas and activation markers of endogenous hippocampal but not cortical microglia, were markedly reduced by CUS, CRS and CSDS treatment. Administration of mice with two classical stimulators of microglia, lipopolysaccharide (LPS) or macrophage colony-stimulating factor (M-CSF), reversed the CUS-, CRS- and CSDS-induced reductions in endogenous hippocampal microglial numbers, and also improved the CUS-, CRS- or CSDS-induced behavioral abnormalities, including the increases in the immobile time in the forced swimming test and tail suspension test, the inhibition of sucrose preference, and the decrease in the time spent in the center of open field. Furthermore, inhibition of the initial activation of hippocampal microglia by minocycline pretreatment also reversed the reduction in hippocampal microglial numbers as well as the behavioral abnormalities induced by CUS, CRS and CSDS treatment. These results provide compelling evidences to show that different types of chronic stresses can trigger the loss of endogenous hippocampal microglia and restoration of microglial numbers may have therapeutic values in major depression.

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“…Before experiments started, all the mice were housed 5 per cage for one week under standard conditions (free access to food and water; lights from 07 : 00 to 19:00; room temperature 24±1°C), as we previously described. [29][30][31][32] All the behavioral experiments were performed during the day. All the procedures involving mice were conducted in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and with the Euro- Morris Water Maze The Morris water maze was conducted as we previously did.…”

Section: Animalsmentioning

confidence: 99%

“…29,35) Western Blotting Analysis The Western blotting method was also performed as we previously did. [29][30][31][32] Quantitative Real-Time Reverse Transcription PCR (qRT-PCR) Dectection The miR-206-3p, miR-206-5p, and BDNF mRNA levels were determined using qRT-PCR method. 28,[36][37][38] For the detection of miR-206, total miRNAs were isolated from the hippocampus and cortex using the mirVana miRNA isolation kit (Ambion, CA, U.S.A.).…”

Section: Animalsmentioning

confidence: 99%

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

Wang

et al. 2017

Biological & Pharmaceutical Bulletin

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Alzheimer's disease (AD) is a most serious age-related neurodegenerative disorder accompanied with significant memory impairments in this world. Recently, microRNAs (miRNAs) have been reported to be invlolved in the pathophysiology of AD. Previous studies have shown that miRNA-206 (miR-206) is implicated in the pathogenesis of AD via suppressing the expression of brain-derived neurotrophic factor (BDNF) in the brain. Here, we examined the miR-206-3p and miR-206-5p expression in the hippocampus and cortex of Abeta precursor protein (APP)/presenilin-1 (PS1) transgenic mice treated with donepezil, a drug approved for treating AD in clinic. We found that the expression of miR-206-3p was significantly up-regulated in the hippocampus and cortex of APP/PS1 mice, while donepezil administration significantly reversed this dysfunction. In addition, enhancing the miR-206-3p level by the usage of AgomiR-206-3p significantly attenuated the anti-dementia effects of donepezil in APP/PS1 mice. Together, these results suggested that miR-206-3p is involved in the anti-dementia effects of donepezil, and could be a novel pharmacological target for treating AD.Key words Alzheimer's disease; brain-derived neurotrophic factor; donepezil; microRNA (miRNA)-206-3pAlzheimer's disease (AD) is a serious neurodegenerative disorder in old people, and always accompanied with significant memory impairments, affecting mainly the hippocampus and frontal cortex. 1,2) AD patients display relatively slow, chronic but progressive neurodegeneration and memory impairments, ultimately leading to full dementia.3,4) Recent survey found that AD is responsible for about 50-60% of all cases of dementia in people over age 65. 3,4) The etiology of AD remains unclear, though many pathophysiologic hallmarks of this disease have been disclosed and are currently well established. They involve a complex network of interconnected factors such as cholinergic dysfunction, aggregation and accumulation of β-amyloid (Aβ), intracellular formation of neurofibrillary tangles composed by tau, oxidative stress, neuronal loss, and so on.5-8) A lot of reports have shown that brain-derived neurotrophic factor (BDNF) is critical for the establishment and maintenance of memory, while the dysfunction of BDNF system leads to memory impairments.9,10) It is known that BDNF combines to tyrosine kinase receptor B (TrkB) in the cell membrane, and then inducing the activation of several intracellular signaling pathways.11-13) Accumulating evidences have indicated that BDNF is implicated in the pathophysiology of AD. Previous studies have already found the reduced expression of BDNF in several brain regions (especially the hippocampus) of postmortem AD samples.14,15) By using the immunohistochemical method, Connor et al. found a significant reduction in not only intensity, but also the number of BDNF-immunoreactive cell in the hippocampus and cortex of AD samples.16) In addition, it was also thought that the Aβ-induced neurotoxicity and dendrite atrophy may due to a consequence of BDNF def...

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WY14643 produces anti-depressant-like effects in mice via the BDNF signaling pathway

Abstract: These data provide the first evidence that WY14643 exerts anti-depressant-like activity through promoting the BDNF signaling pathway.

Cited by 45 publications

References 54 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

Microglia Loss Contributes to the Development of Major Depression Induced by Different Types of Chronic Stresses

The Anti-dementia Effects of Donepezil Involve miR-206-3p in the Hippocampus and Cortex

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