Medial Ganglionic Eminence Cells Freshly Obtained or Expanded as Neurospheres Show Distinct Cellular and Molecular Properties in Reducing Epileptic Seizures

Medial Ganglionic Eminence Cells Freshly Obtained or Expanded as Neurospheres Show Distinct Cellular and Molecular Properties in Reducing Epileptic Seizures

Author Romariz, Simone A. A. Autor UNIFESP Google Scholar
Paiva, Daisylea S. Autor UNIFESP Google Scholar
Galindo, Layla T. Autor UNIFESP Google Scholar
Barnabe, Gabriela F. Google Scholar
Guedes, Vivian A. Google Scholar
Borlongan, Cesario V. Google Scholar
Longo, Beatriz M. Autor UNIFESP Google Scholar
Abstract AimsMedial ganglionic eminence (MGE) progenitors give rise to inhibitory interneurons and may serve as an alternative cell source for large-scale cell transplantation for epilepsy after in vitro expansion. We investigated whether modifications in the culture medium of MGE neurospheres affect neuronal differentiation and expression of MGE-specific genes. In vivo, we compared anticonvulsant effects and cell differentiation pattern among neurospheres grown in different culture media and compared them with freshly harvested MGE cells. MethodsWe used four variations of cell culture: standard, containing growth factors (EGF/FGF-2) (GF)

addition of retinoic acid (GF-RA)

withdrawal of EGF/FGF-2 (WD)

and addition of retinoic acid and withdrawal of EGF/FGF-2 (WD-RA). Based on in vitro results neurosphere-grown (WD-RA or GF conditions) or fresh MGE cells were transplanted into the hippocampus. ResultsIn vitro WD-RA showed increased neuronal population and higher expression of Dlx1, Nkx2.1, and Lhx6 genes in comparison with GF culture condition. After transplantation, fresh MGE cells and neurospheres (GF) showed anticonvulsant effects. However, fresh MGE cells differentiated preferentially into inhibitory neurons, while GF gave rise to glial cells. ConclusionWe conclude that freshly isolated and neurosphere-grown MGE cells reduced seizures by different mechanisms (inhibitory interneurons vs. astrocytes). Fresh MGE cells appear more appropriate for cell therapies targeting inhibitory interneurons for conferring anticonvulsant outcomes.
Keywords Epilepsy
Interneuronal progenitors
Medial ganglionic eminence
Neurospheres
Transplantation
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Sponsor FAPESP
CNPq
Date 2017
Published in Cns Neuroscience & Therapeutics. Hoboken, v. 23, n. 2, p. 127-134, 2017.
ISSN 1755-5930 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 127-134
Origin http://dx.doi.org/10.1111/cns.12650
Access rights Closed access
Type Article
Web of Science ID WOS:000394157900003
URI https://repositorio.unifesp.br/handle/11600/55186

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