Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test

Boucher, Aurélie A.; Arnold, Jonathon C.; Hunt, Glenn E.; Spiro, Adena S.; Spencer, Jarrah R.; Brown, C.; McGregor, Iain S.; Bennett, Maxwell R.; Kassiou, Michael

doi:10.1016/j.neuroscience.2011.05.049

Cited by 100 publications

(83 citation statements)

References 44 publications

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“…39) Deletion of P2X7 exerted antidepressive effects as evidenced by longer swim times and increased mobility in the forced swim and tail suspension tests in mice. 40) It should be mentioned that P2X7 receptor was identified as a key player in the process of microglia activation. In the quiescent microglia, P2X7 is permeable to small cations while in the reactive microglia P2X7 was converted to the pore status, which facilitates the release of pro-inflammatory cytokines TNF-α and IL-1β from microglia.…”

Section: Discussionmentioning

confidence: 99%

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Tan

Wang

Chen

et al. 2017

Biological & Pharmaceutical Bulletin

125

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The purpose of the present study was to investigate whether ketamine's rapid antidepressant effects were associated with its anti-inflammatory actions and to explore the underlying molecular mechanism. Depressive-like behaviors was induced in mice using chronic restraint stress (CRS) method. Anti-depressive effects of ketamine were evaluated by forced swimming tests (FST) and sucrose preference test (SPT). Subsequently, brain tissue was harvested to investigate inflammatory response in the hippocampus via investigating reactive microglia numbers, serum cytokines levels and the toll-like receptor type 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) pathway. CRS exposure caused depressive-like behaviors in mice, which was associated with increased pre-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6) levels, reactive microglia numbers and up-regulated regulatory molecules such as TLR4/p38 and P2X7 receptor in hippocampus. Such neurobehavioral and biochemical abnormalities were normalized by ketamine treatment. CRS-induced depression-like behaviours are associated with activation of hippocampal inflammatory response, whereas down-regulation of pro-inflammatory cytokines may contribute to ketamine's antidepressant effects in mice.

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Section: Discussionmentioning

confidence: 99%

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Tan

Wang

Chen

et al. 2017

Biological & Pharmaceutical Bulletin

125

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“…In rodent studies mimicking depressive-like behaviors, both genetic deletion and pharmacological inhibition of P2X7 receptors lead to an antidepressant phenotype, which is manifested in the widely used forced swim (FST) and tail suspension tests (TST) (Basso et al, 2009;Boucher et al, 2011;Csolle et al, 2013a,b;Pereira et al, 2013;Wilkinson et al, 2014), but can also be measured using more complex paradigms such as learned helplessness (Iwata et al, 2013). Acute stress induced depressiveelike behaviors, following LPS challenge are also alleviated by P2X7 receptor antagonism, (Csolle et al, 2013b;Ma et al, 2014).…”

Section: Purinergic Regulation Of Neuroinflammation In Cns Disordersmentioning

confidence: 99%

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

et al. 2016

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a b s t r a c tThe principle functions of neuroinflammation are to limit tissue damage and promote tissue repair in response to pathogens or injury. While neuroinflammation has utility, pathophysiological inflammatory responses, to some extent, underlie almost all neuropathology. Understanding the mechanisms that control the three stages of inflammation (initiation, propagation and resolution) is therefore of critical importance for developing treatments for diseases of the central nervous system. The purinergic signaling system, involving adenosine, ATP and other purines, plus a host of P1 and P2 receptor subtypes, controls inflammatory responses in complex ways. Activation of the inflammasome, leading to release of pro-inflammatory cytokines, activation and migration of microglia and altered astroglial function are key regulators of the neuroinflammatory response. Here, we review the role of P1 and P2 receptors in mediating these processes and examine their contribution to disorders of the nervous system. Firstly, we give an overview of the concept of neuroinflammation. We then discuss the contribution of P2X, P2Y and P1 receptors to the underlying processes, including a discussion of cross-talk between these different pathways. Finally, we give an overview of the current understanding of purinergic contributions to neuroinflammation in the context of specific disorders of the central nervous system, with special emphasis on neuropsychiatric disorders, characterized by chronic low grade inflammation or maternal inflammation. An understanding of the important purinergic contribution to neuroinflammation underlying neuropathology is likely to be a necessary step towards the development of effective interventions.

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“…18 It has also been recently shown that P2X 7 R knockout (KO) mice show resilience in the FST (i.e., increased mobility compared to WT mice), an observation which both validates the use of such a behavioral model for this target and also provides a maximal response benchmark for P2X 7 R antagonism. 19 Prior to the FST, a drug tolerability test was performed on the mice with doses up to 20 mg/kg showing no adverse effects to body temperature, locomotor activity, or body weight (see the Supporting Information). The mice were then injected with 20 mg/kg of 1−4 and Cs·5 or vehicle and subjected to a 6 min FST.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

The First CNS-Active Carborane: A Novel P2X₇ Receptor Antagonist with Antidepressant Activity

Wilkinson¹,

Gunosewoyo²,

Barron³

et al. 2014

ACS Chem. Neurosci.

128

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Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test

Cited by 100 publications

References 44 publications

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

The First CNS-Active Carborane: A Novel P2X₇ Receptor Antagonist with Antidepressant Activity

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Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test

Cited by 100 publications

References 44 publications

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Ketamine Alleviates Depressive-Like Behaviors <i>via</i> Down-Regulating Inflammatory Cytokines Induced by Chronic Restraint Stress in Mice

Purinergic mechanisms in neuroinflammation: An update from molecules to behavior

The First CNS-Active Carborane: A Novel P2X7 Receptor Antagonist with Antidepressant Activity

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Product

Resources

About

The First CNS-Active Carborane: A Novel P2X₇ Receptor Antagonist with Antidepressant Activity