| First Author | Lykhmus O | Year | 2019 |
| Journal | Neuroscience | Volume | 413 |
| Pages | 31-44 | PubMed ID | 31202708 |
| Mgi Jnum | J:282981 | Mgi Id | MGI:6384389 |
| Doi | 10.1016/j.neuroscience.2019.06.004 | Citation | Lykhmus O, et al. (2019) Mesenchymal Stem Cells or Interleukin-6 Improve Episodic Memory of Mice Lacking alpha7 Nicotinic Acetylcholine Receptors. Neuroscience 413:31-44 |
| abstractText | Nicotinic acetylcholine receptors of alpha7 subtype (alpha7 nAChRs) are involved in regulating cognition, inflammation and cell survival. Neuroinflammation is accompanied by the decrease of alpha7 nAChRs in the brain and impairment of memory. We show here that alpha7-/- mice possess pro-inflammatory phenotype and demonstrate worse episodic memory compared to wild-type mice. Previously we reported that mesenchymal stem cells (MSCs) restored episodic memory of lipopolysaccharide-treated wild-type mice. The aim of this study was to examine if MSCs or their soluble factors improve memory of alpha7-/- mice. The alpha7-specific signal (ELISA) and alpha7+ cells (IHC) were found in the brain of alpha7-/- mice on days 7 and 14 after intravenous injection of alpha7+ MSCs from either human umbilical cord (hMSCs) or mouse placenta (mMSCs). The intravenously injected MSCs or intraperitoneally injected hMSCs-conditioned medium transiently improved episodic memory of alpha7-/- mice and decreased cytochrome c release from their brain mitochondria under the effect of Ca2+. Either MSCs or conditioned medium stimulated an IL-6 increase in the brain, which coincided with the improvement of episodic memory. Injections of recombinant IL-6 also improved episodic memory of alpha7-/- mice accompanied by the up-regulation of alpha3, alpha4, beta2 and beta4 nAChR subunits in the brain. It is concluded that MSCs, injected intravenously, penetrate the brain of alpha7-/- mice and persist there for at least 2 weeks. They improve episodic memory of mice and make their mitochondria more resistant to apoptogenic influence. One of the soluble factors responsible for the memory improvement is IL-6. |
