Structural and functional characteristics of the hippocampus in depressive-like recipients after transplantation of in vitro caffeine-modulated immune cells

Neurosci Lett. 2022 Aug 24:786:136790. doi: 10.1016/j.neulet.2022.136790. Epub 2022 Jul 15.

Abstract

The hippocampus is a key anatomical brain region associated with depression. On the other hand, immune cells and their releasing cytokines play an essential role in stress and depression. Noteworthy that the most of psychoactive drugs produce unidirectional effects on the cells of both nervous and immune systems. This suggests the immunotherapy for behavioral disorders based on the treatment with autologous immune cells in which functional activity was modulated ex vivo by a psychoactive drug. Here, we treated the immune cells of depressive-like mice in vitro with caffeine (100 μg per 15 × 106 cells). The effects of caffeine-treated immune cells transplantation on neuronal density, production of brain-derived neurotrophic factor (BDNF) and a number of cytokines in the hippocampus of depressive-like syngeneic animals were studied. In depressive-like recipients, an increase in the density of pyramidal neurons in CA1 and CA3 hippocampal regions, accompanied with augmented level of BDNF, decreased levels of pro-inflammatory (IL-1β, IL-6, INF-γ, and TNF-α) and increased levels of anti-inflammatory (IL-10 and IL-4) cytokines was found. The mechanisms of the revealed structural and functional alterations in the hippocampus of depressive-like recipients after transplantation of caffeine-treated immune cells are discussed.

Keywords: Brain-derived neurotrophic factor; Cytokines; Depression; Mice; Modulated immune cells.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Caffeine* / pharmacology
  • Cytokines / metabolism
  • Depression
  • Disease Models, Animal
  • Hippocampus / metabolism
  • Mice

Substances

  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Caffeine