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Cited by 83Adenosine and Purinergic SignalingStress Responses and CortisolTreatment of Major Depression

A P2X7 receptor antagonist reverses behavioural alterations, microglial activation and neuroendocrine dysregulation in an unpredictable chronic mild stress (UCMS) model of depression in mice

Farooq, Rai Khalid, Tanti, Arnaud, Ainouche, Samia, Roger, Sébastien, Belzung, Catherine, Camus, Vincent·2018·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2018.07.016
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Abstract

A polymorphism in the P2RX7 gene that encodes for the P2X7 ionotropic ATP-gated receptor (P2X7R) protein has been shown to be associated with an increased risk for developing depressive illnesses. However, the role of P2X7R in depression is still unclear. To better understand the role of P2X7R and its subsequent impact on microglial activation, we compared the effect of the P2X7R antagonist Brilliant Blue G (BBG) with that of fluoxetine in an unpredictable chronic mild stress (UCMS) model of depression in mice. Our results indicate that BBG (50 mg/kg body weight in 0.9% NaCl, 10 ml/kg/day) successfully reversed the degradation of coat states and nest-building scores induced by exposure to UCMS, similar to the conventional antidepressant fluoxetine (15 mg/kg body weight in 0.9% NaCl, 10 ml/kg/day). BBG also reversed the UCMS-induced microglial activation in cortical and hippocampal regions and the basal nuclei of mouse brains and corrected the UCMS-induced hypothalamo-pituitary-adrenal (HPA) axis dysregulation. In contrast to fluoxetine, however, BBG treatment did not increase the density of doublecortin-positive cells in the dentate gyrus, indicating that BBG had no impact on hippocampal neurogenesis. These results suggest that P2X7R is involved in recovery from depressive-like states caused by exposure to UCMS in a mechanism that involves restoration of the HPA axis but not hippocampal neurogenesis. These results add to the evidence that P2X7R antagonist agents may have potential value in the pharmacological management of depression.

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Crossref · 10.1016/j.psyneuen.2018.07.016

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  • Gene knockout or pharmacological inhibition of P2X7 receptors induced antidepressant-like behavior in mice exposed to stress, accompanied by HPA axis restoration.

    “Noteworthy, gene knockout or pharmacological inhibition of P2X7 receptors induced antidepressant-like behavior in mice exposed to stress, accompanied by HPA axis restoration [163, 164].”

    From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [163]

  • Systemic treatment with BBG or fluoxetine during 7 weeks in mice exposed to CUMS reversed the behavioral alterations induced by chronic stress exposure, suggesting an antidepressant-like effect of both interventions.

    “In line with these observations, systemic treatment with BBG (50 mg/kg, per day) or fluoxetine (15 mg/kg, per day) during 7 weeks in mice exposed to CUMS reversed the behavioral alterations induced by the chronic stress exposure, strongly suggesting an antidepressant-like effect of both interventions in the model [88].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [88]

  • Both pharmacological and genetic evidence strongly suggest that P2X7R stimulation during stress increases vulnerability and subsequent development of behavioral adversities associated with the neurobiology of depression.

    “Altogether, both pharmacological and genetic evidence strongly suggest that P2X7R stimulation during stress increase the vulnerability and subsequent development of behavioral adversities associated with the neurobiology of depression (Table 2).”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [88]

  • Systemic treatment for 7 weeks with BBG (50 mg/kg per day) or fluoxetine (15 mg/kg per day) reversed behavioral alterations and microglial activation in cortex, hippocampus and basal nuclei of mice exposed to CUMS.

    “systemic treatment during 7 weeks with BBG (50 mg/kg, per day) or fluoxetine (15 mg/kg, per day) reversed the behavioral alterations and microglial activation in cortex, hippocampus and basal nuclei of mice exposed to CUMS [88].”

    From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [88]

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Authors
Farooq, R. K., Tanti, A., Ainouche, S., Roger, S., Belzung, C., & Camus, V.
Affiliations
  • Université de Tours (FR)
  • Inserm (FR)
Corresponding author
Farooq, Rai Khalid
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2018-11
Volume
97
Pages
120-130
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2018.07.016
OpenAlex
W2858678099
Cited by
83
References
104
Citations by year
2026: 5 · 2025: 3 · 2024: 8 · 2023: 10 · 2022: 18 · 2021: 16 · 2020: 12 · 2019: 7 · 2018: 3
FWCI
7.80
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Alabama Commission on Higher Education
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
P2X7 receptor, Brilliant Blue G, depression, chronic unpredictable mild stress, microglial activation, HPA axis dysregulation, neuroendocrine dysfunction, fluoxetine, hippocampal neurogenesis, doublecortin, nest building behavior, antidepressant treatment
MeSH terms
Animals, Antidepressive Agents, Behavior, Animal, Chronic Disease, Depression, Depressive Disorder, Disease Models, Animal, Fluoxetine, Hippocampus, Hypothalamo-Hypophyseal System, Male, Mice, Inbred BALB C, Neurosecretory Systems, Pituitary-Adrenal System, Rosaniline Dyes, Stress, Psychological, Microglia, Dentate Gyrus, Mice, Neurogenesis, Receptors, Purinergic P2X7, Purinergic P2X Receptor Antagonists

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