Neuropeptides including oxytocin belong to the group of factors that may play a role in the control of neuronal cell survival, proliferation and differentiation. The aim of the present study was to investigate potential contribution of oxytocin to neuronal differentiation by measuring gene and protein expression of specific neuron and glial markers in the brain. Neonatal and adult oxytocin administration was used to reveal developmental and/or acute effects of oxytocin in Wistar rats. Gene and protein expression of neuron-specific enolase (NSE) in the hippocampus was increased in 21-day and 2-month old rats in response to neonatal oxytocin administration. Neonatal oxytocin treatment induced a significant increase of gene and protein expression of the marker of astrocytes - glial fibrillary acid protein (GFAP). Oxytocin treatment resulted in a decrease of oligodendrocyte marker mRNA - 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) - in 21-day and 2-month old rats, while no change of CD68 mRNA, marker of microglia, was observed. Central oxytocin administration in adult rats induced a significant increase of gene expression of NSE and CNPase. The present study provides the first data revealing the effect of oxytocin on the expression of neuron and glial markers in the brain. It may be suggested that the oxytocin system is involved in the regulation of development of neuronal precursor cells in the brain.
- MeSH
- 2',3'-cyklické nukleotidfosfodiesterasy genetika MeSH
- antigeny diferenciační myelomonocytární genetika MeSH
- CD antigeny genetika MeSH
- hipokampus cytologie účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- neuroglie cytologie účinky léků metabolismus MeSH
- neurony cytologie účinky léků metabolismus MeSH
- oxytocin farmakologie MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Despite advances in our understanding and research of induced pluripotent stem cells (iPSCs), their use in clinical practice is still limited due to lack of preclinical experiments. Neural precursors (NPs) derived from a clone of human iPSCs (IMR90) were used to treat a rat spinal cord lesion 1 week after induction. Functional recovery was evaluated using the BBB, beam walking, rotarod, and plantar tests. Lesion morphology, endogenous axonal sprouting, graft survival, and iPSC-NP differentiation were analyzed immunohistochemically. Quantitative polymerase chain reaction (qPCR) was used to evaluate the effect of transplanted iPSC-NPs on endogenous regenerative processes and also to monitor their behavior after transplantation. Human iPSC-NPs robustly survived in the lesion, migrated, and partially filled the lesion cavity during the entire period of observation. Transplanted animals displayed significant motor improvement already from the second week after the transplantation of iPSC-NPs. qPCR revealed the increased expression of human neurotrophins 8 weeks after transplantation. Simultaneously, the white and gray matter were spared in the host tissue. The grafted cells were immunohistochemically positive for doublecortin, MAP2, βIII-tubulin, GFAP, and CNPase 8 weeks after transplantation. Human iPSC-NPs further matured, and 17 weeks after transplantation differentiated toward interneurons, dopaminergic neurons, serotoninergic neurons, and ChAT-positive motoneurons. Human iPSC-NPs possess neurotrophic properties that are associated with significant early functional improvement and the sparing of spinal cord tissue. Their ability to differentiate into tissue-specific neurons leads to the long-term restoration of the lesioned tissue, making the cells a promising candidate for future cell-based therapy of SCI.
- MeSH
- 2',3'-cyklické nukleotidfosfodiesterasy genetika metabolismus MeSH
- buněčná diferenciace MeSH
- chování zvířat MeSH
- gliový fibrilární kyselý protein genetika metabolismus MeSH
- hematoencefalická bariéra metabolismus MeSH
- indukované pluripotentní kmenové buňky cytologie metabolismus MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- nervové kmenové buňky cytologie transplantace MeSH
- neurotrofní faktory genetika metabolismus MeSH
- pohyb buněk MeSH
- pohybová aktivita MeSH
- poranění míchy etiologie terapie MeSH
- potkani Wistar MeSH
- proteiny asociované s mikrotubuly genetika metabolismus MeSH
- transkripční faktory genetika metabolismus MeSH
- transplantace heterologní MeSH
- tubulin genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
