Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP + cells loss induced by restraint stress in mice

Nelson Perez-Urrutia, Cristhian Mendoza, Nathalie Alvarez-Ricartes, Patricia Oliveros-Matus, Florencia Echeverria, J. Alex Grizzell, George E. Barreto, Alexandre Iarkov, Valentina Echeverria

Research output: Contribution to journalArticlepeer-review

Abstract

Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP + immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress. The results revealed that in addition to the mood and cognitive impairments, restraint stress induced a significant decrease in the number and arborization of GFAP + cells in the brain of mice. Intranasal cotinine prevented these stress-derived symptoms and the morphological abnormalities GFAP + cells in both of these brain regions which are critical to resilience to stress. The significance of these findings for the therapy of PTSD and depression is discussed.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalExperimental Neurology
Volume295
DOIs
Publication statusPublished - Sep 2017

Keywords

  • Astrocytes
  • Cotinine
  • Depression
  • Memory
  • Stress

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