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Open Access Highly Accessed Research article

Long-lasting anxiolytic effect of neural precursor cells freshly prepared but not neurosphere-derived cell transplantation in newborn rats

Simone Amaro Alves Romariz1, Daisyléa de Souza Paiva1, Maria Fernanda Valente1, Gabriela Filoso Barnabé1, Roberto Frussa-Filho2, Regina Cláudia Barbosa-Silva3, Maria Elisa Calcagnotto4 and Beatriz Monteiro Longo1*

Author Affiliations

1 Departamento de Fisiologia, UNIFESP, Rua Botucatu, 862, 5° andar, 04023-062 São Paulo, SP, Brazil

2 Departamento de Farmacologia, UNIFESP, Rua Botucatu, 862, 04023-062 São Paulo, SP, Brazil

3 Departamento de Biociências, UNIFESP, Rua Silva Jardim, 136, 11015-020 Santos, SP, Brazil

4 Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, 90035-003 Porto Alegre, RS, Brazil

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BMC Neuroscience 2014, 15:94  doi:10.1186/1471-2202-15-94

Published: 2 August 2014

Abstract

Background

The GABAergic system plays an important role in modulating levels of anxiety. When transplanted into the brain, precursor cells from the medial ganglionic eminence (MGE) have the ability to differentiate into GABAergic interneurons and modify the inhibitory tone in the host brain. Currently, two methods have been reported for obtaining MGE precursor cells for transplantation: fresh and neurosphere dissociated cells. Here, we investigated the effects generated by transplantation of the two types of cell preparations on anxiety behavior in rats.

Results

We transplanted freshly dissociated or neurosphere dissociated cells into the neonate brain of male rats on postnatal (PN) day 2–3. At early adulthood (PN 62–63), transplanted animals were tested in the Elevated Plus Maze (EPM). To verify the differentiation and migration pattern of the transplanted cells in vitro and in vivo, we performed immunohistochemistry for GFP and several interneuron-specific markers: neuropeptide Y (NPY), parvalbumin (PV) and calretinin (CR). Cells from both types of preparations expressed these interneuronal markers. However, an anxiolytic effect on behavior in the EPM was observed in animals that received the MGE-derived freshly dissociated cells but not in those that received the neurosphere dissociated cells.

Conclusion

Our results suggest a long-lasting anxiolytic effect of transplanted freshly dissociated cells that reinforces the inhibitory function of the GABAergic neuronal circuitry in the hippocampus related to anxiety-like behavior in rats.

Keywords:
Anxiety; Medial ganglionic eminence; Neuronal precursor cells; Transplantation