Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway

Azogu, Idu; Plamondon, Hélène

doi:10.1016/j.yhbeh.2017.02.012

Cited by 16 publications

(8 citation statements)

References 115 publications

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“…BDNF plays an important role in maintaining trophism in the adult brain, and in controlling longterm potentiation (LTP) with important implications for learning and memory and emotional behaviour (Azogu and Plamondon, 2017;Famitafreshi et al, 2016;Li and Li, 2015). BDNF has also been implicated in pain, inflammation and convulsive activity (Smith, 2014).…”

Section: Discussionmentioning

confidence: 99%

Are preconceptional stressful experiences crucial elements for the aetiology of autism spectrum disorder? Insights from an animal model

et al. 2019

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Section: Discussionmentioning

confidence: 99%

Are preconceptional stressful experiences crucial elements for the aetiology of autism spectrum disorder? Insights from an animal model

et al. 2019

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“…On one hand, GR antagonists impeded stress-induced sensitization of the mesolimbic pathway but on the other hand, GR agonists prevented behavioral vulnerability to stress in corticolimbic areas (45)(46)(47). This reflects decreased GR expression in prefrontal cortex and hippocampus, and increased GR expression in the amygdala upon stress (48)(49)(50)(51). Epigenetic reprogramming sets the stage for changes in GR expression associated with significant risk of depression and suicide (52,53).…”

Section: Bridging the Gap Between Bdnf And Glucocorticoid Effects In mentioning

confidence: 99%

Bridging the Gap between Brain-Derived Neurotrophic Factor and Glucocorticoid Effects on Brain Networks

et al. 2018

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Behavioral choices made by the brain during stress depend on glucocorticoid and BDNF signaling pathways acting in synchrony in the mesolimbic (reward) and corticolimbic (emotion) neural networks. Deregulated expression of BDNF and glucocorticoid receptors in brain valuation areas may compromise integration of signals. Glucocorticoid receptor phosphorylation upon BDNF signaling in neurons represents one mechanism underlying the integration of BDNF and glucocorticoid signals that when off balance may lay the foundation of maladaptations to stress.Here, we propose that BDNF signaling conditions glucocorticoid responses impacting neural plasticity in the mesocorticolimbic system. This provides a novel molecular framework for understanding how brain networks use BDNF and glucocorticoid signaling contingencies to forge receptive neuronal fields in temporal domains defined by behavioral experience, and in mood disorders. Introduction Cooperation between the mesolimbic and corticolimbic systems determines behavioral choicesBrain region-specific effects of BDNF and glucocorticoids on the mesocorticolimbic system Bridging the gaps between BDNF and glucocorticoid effects in the mesocorticolimbic system GR phosphorylation is influenced by BDNF signaling Effect of BDNF and glucocorticoid signaling in health and disease Summary References

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“…Melo et al found that in hippocampal neurons in vitro , the expression levels of VGluT2 were significantly upregulated after exogenous BDNF stimulation, while TrkB inhibitors inhibited the upregulated expression of VGluT2 induced by BDNF, indicating that the BDNF/TrkB pathway participates in regulating the expression of VGluT2 ( Melo et al, 2013 ). Another study by Azogu et al found that the injection of TrkB antagonist ANA-12 in the nucleus accumbens could reduce anxious behaviors in stressed rats and lead to the downregulation of VGluT2 expression in the hypothalamus and amygdala ( Azogu and Plamondon, 2017 ). However, the role of the BDNF/TrkB pathway in the regulation of VGluT2 in the spinal cord has not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that the BDNF/TrkB pathway participates in the modulation of VGluT2 expression in isolated hippocampal neurons ( Melo et al, 2013 ). Moreover, administration of the TrkB antagonist ANA-12 in the nucleus accumbens reduced VGluT2 expression in the hypothalamus and basolateral amygdala ( Azogu and Plamondon, 2017 ). Based on this, we hypothesized that the BDNF/TrkB pathway regulates the expression of VGluT2 in the spinal cord, contributing to the development of morphine tolerance in mice.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of Vesicular Glutamate Transporter VGluT2 via BDNF/TrkB Pathway Contributes to Morphine Tolerance in Mice

Zhang

et al. 2022

Front. Pharmacol.

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Morphine is widely used in the treatment of moderate to severe pain. Long-term use of morphine leads to various adverse effects, such as tolerance and hyperalgesia. Vesicular glutamate transporter 2 (VGluT2) accumulates glutamate into synaptic vesicles and plays multiple roles in the central nervous system. However, the specific role of VGluT2 in morphine tolerance has not been fully elucidated. Here, we investigated the regulatory role of VGluT2 in morphine tolerance and assessed the potential role of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) pathway in VGluT2 mediated morphine antinociceptive tolerance in mice. In the present study, we found that VGluT2 is upregulated in the spinal cord after the development of morphine tolerance. Furthermore, inhibition of VGluT2 with its antagonist (Chicago sky blue 6 B, CSB6B) or knockdown of VGluT2 by lentivirus restored the analgesic effect of morphine, suppressed the activation of astrocytes and microglia, and decreased glial-derived pro-inflammatory cytokines. Overexpression of VGluT2 by lentivirus facilitated morphine tolerance and mechanical hyperalgesia. In addition, we found the expression of BDNF is correlated with VGluT2 expression in the spinal cord after chronic morphine administration. Intrathecal injection of the BDNF/TrkB pathway antagonist K252a attenuated the development of morphine tolerance and decreased the expression of VGluT2 in the spinal cord, which suggested the BDNF/TrkB pathway participates in the regulation of VGluT2 in morphine tolerance. This study elucidates the functional capability of VGluT2 in modulating morphine tolerance and identifies a novel mechanism and promising therapeutic target for morphine tolerance.

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Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway

Cited by 16 publications

References 115 publications

Are preconceptional stressful experiences crucial elements for the aetiology of autism spectrum disorder? Insights from an animal model

Are preconceptional stressful experiences crucial elements for the aetiology of autism spectrum disorder? Insights from an animal model

Bridging the Gap between Brain-Derived Neurotrophic Factor and Glucocorticoid Effects on Brain Networks

Dysregulation of Vesicular Glutamate Transporter VGluT2 via BDNF/TrkB Pathway Contributes to Morphine Tolerance in Mice

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