The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo

L. Lecanu, A. I. Hashim, A. McCourty, I. Giscos-Douriez, I. Dinca, W. Yao, S. Vicini, G. Szabo, F. Erdélyi, J. Greeson, V. Papadopoulos

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Abstract

In this study, we explored the capacity of the naturally occurring compound solasodine to promote neurogenesis in vitro and in vivo. Mouse embryonic teratocarcinoma P19 cells exposed to solasodine for 2 days followed by a 5-day washout differentiated into cholinergic neurons that expressed specific neuronal markers and displayed important axonal formation that continued growing even 30 days after treatment. In vivo, a 2-week infusion of solasodine into the left ventricle of the rat brain followed by a 3-week washout resulted in a significant increase in bromodeoxyuridine uptake by cells of the ependymal layer, subventricular zone, and cortex that co-localized with doublecortin immunostaining, demonstrating the proliferative and differentiating properties of solasodine on neuronal progenitors. In addition, these data demonstrate that under our experimental conditions adult ependymal cells retrieved their proliferative and differentiating abilities. The GAP-43/HuD pathway was activated both in vitro and in vivo, suggesting a role in the differentiating process triggered by solasodine. Solasodine treatment in rats resulted in a dramatic increase in expression of the cholesterol- and drug-binding translocator protein in ependymal cells, suggesting a possible role played by neurosteroid production in solasodine-induced neurogenesis. In GAD65-GFP mice that express the green fluorescent protein under the control of the glutamic acid decarboxylase 65-kDa promoter, solasodine treatment increased the number of GABAergic progenitors and neuroblasts generated in the subventricular zone and present in the olfactory migratory tract. Taken together, these results suggest that solasodine offers an interesting approach to stimulate in situ neurogenesis from resident neuronal progenitors as part of neuron replacement therapy.

Original languageEnglish
Pages (from-to)251-264
Number of pages14
JournalNeuroscience
Volume183
DOIs
Publication statusPublished - Jun 2 2011

Fingerprint

Neurogenesis
Steroids
Lateral Ventricles
Teratocarcinoma
GAP-43 Protein
solasodine
In Vitro Techniques
Cholinergic Neurons
Glutamate Decarboxylase
Olfactory Bulb
Bromodeoxyuridine
Green Fluorescent Proteins
Heart Ventricles
Neurotransmitter Agents
Carrier Proteins
Cholesterol
Neurons
Brain

Keywords

  • GAP43
  • Neurogenesis
  • Neurosteroids
  • Solasodine
  • Subventricular zone
  • TSPO

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lecanu, L., Hashim, A. I., McCourty, A., Giscos-Douriez, I., Dinca, I., Yao, W., ... Papadopoulos, V. (2011). The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. Neuroscience, 183, 251-264. https://doi.org/10.1016/j.neuroscience.2011.03.042

The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. / Lecanu, L.; Hashim, A. I.; McCourty, A.; Giscos-Douriez, I.; Dinca, I.; Yao, W.; Vicini, S.; Szabo, G.; Erdélyi, F.; Greeson, J.; Papadopoulos, V.

In: Neuroscience, Vol. 183, 02.06.2011, p. 251-264.

Research output: Contribution to journalArticle

Lecanu, L, Hashim, AI, McCourty, A, Giscos-Douriez, I, Dinca, I, Yao, W, Vicini, S, Szabo, G, Erdélyi, F, Greeson, J & Papadopoulos, V 2011, 'The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo', Neuroscience, vol. 183, pp. 251-264. https://doi.org/10.1016/j.neuroscience.2011.03.042
Lecanu L, Hashim AI, McCourty A, Giscos-Douriez I, Dinca I, Yao W et al. The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. Neuroscience. 2011 Jun 2;183:251-264. https://doi.org/10.1016/j.neuroscience.2011.03.042
Lecanu, L. ; Hashim, A. I. ; McCourty, A. ; Giscos-Douriez, I. ; Dinca, I. ; Yao, W. ; Vicini, S. ; Szabo, G. ; Erdélyi, F. ; Greeson, J. ; Papadopoulos, V. / The naturally occurring steroid solasodine induces neurogenesis in vitro and in vivo. In: Neuroscience. 2011 ; Vol. 183. pp. 251-264.
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