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P2X7 Receptors DriveSpine SynapsePlasticity in theLearned HelplessnessModel of Depression Lilla OtrokocsiÁgnes KittelBeáta Sperlágh2017 год

P2X7 Receptors Drive Spine Synapse Plasticity in the Learned Helplessness Model of Depression
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Аннотация: 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. 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. 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. 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.
Год издания: 2017
Авторы: Lilla Otrokocsi, Ágnes Kittel, Beáta Sperlágh
Издательство: University of Oxford
Источник: The International Journal of Neuropsychopharmacology
Ключевые слова: Adenosine and Purinergic Signaling, Bipolar Disorder and Treatment, Electroconvulsive Therapy Studies
Другие ссылки: The International Journal of Neuropsychopharmacology (PDF)
The International Journal of Neuropsychopharmacology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)