P2X7 receptors drive spine synapse plasticity in the learned helplessness model of depression

Lilla Otrokocsi, A. Kittel, B. Sperlágh

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Major depressive disorder is characterized by structural and functional abnormalities of cortical and limbic brain areas, including a decrease in spine synapse number in the dentate gyrus of the hippocampus. Recent studies highlighted that both genetic and pharmacological invalidation of the purinergic P2X7 receptor (P2rx7) leads to antidepressant-like phenotype in animal experiments; however, the impact of P2rx7 on depression-related structural changes in the hippocampus is not clarified yet. Methods: Effects of genetic deletion of P2rx7s on depressive-like behavior and spine synapse density in the dentate gyrus were investigated using the learned helplessness mouse model of depression. Results: We demonstrate that in wild-type animals, inescapable footshocks lead to learned helplessness behavior reflected in increased latency and number of escape failures to subsequent escapable footshocks. This behavior is accompanied with downregulation of mRNA encoding P2rx7 and decrease of spine synapse density in the dentate gyrus as determined by electron microscopic stereology. In addition, a decrease in synaptopodin but not in PSD95 and NR2B/GluN2B protein level was also observed under these conditions. Whereas the absence of P2rx7 was characterized by escape deficit, no learned helpless behavior is observed in these animals. Likewise, no decrease in spine synapse number and synaptopodin protein levels was detected in response to inescapable footshocks in P2rx7-deficient animals. Conclusion: Our findings suggest the endogenous activation of P2rx7s in the learned helplessness model of depression and decreased plasticity of spine synapses in P2rx7-deficient mice might explain the resistance of these animals to repeated stressful stimuli.

Original languageEnglish
Pages (from-to)813-822
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

Fingerprint

Purinergic P2X7 Receptors
Learned Helplessness
Synapses
Spine
Depression
Dentate Gyrus
Parahippocampal Gyrus
Wild Animals
Major Depressive Disorder
Antidepressive Agents
Hippocampus
Proteins
Down-Regulation
Drive
Pharmacology
Electrons
Phenotype
Messenger RNA
Brain

Keywords

  • Depression
  • Learned helplessness
  • P2rx7
  • Spine synapse

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

P2X7 receptors drive spine synapse plasticity in the learned helplessness model of depression. / Otrokocsi, Lilla; Kittel, A.; Sperlágh, B.

In: International Journal of Neuropsychopharmacology, Vol. 20, No. 10, 01.10.2017, p. 813-822.

Research output: Contribution to journalArticle

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