AMPA and ampakines as proneurogenic modulators of progenitors derived from subventricular zone
-
1
Universidade de Coimbra, Centro de Neurociencias e Biologia Celular, Portugal
Neurogenesis in the brain of adult mammals occurs throughout life, and has been demonstrated at two locations under normal conditions: the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus.
AMPAkines are a group of chemical compounds that modulate the properties of ionotropic AMPA subtype of glutamate receptors, potentiating excitatory signals and enhancing cognitive properties. AMPAkine effects are presumably mediated through increase in synaptic efficiency of excited neuronal circuits. However, a positive effect on neurogenesis cannot be ruled out. Here, we propose to disclose the pro-neurogenic effects of an excitatory stimulation, through AMPA treatment, and AMPAkines in SVZ cell cultures derived from neonatal mice.
SVZ cells were incubated in the presence of AMPA (1 to 50μM) and AMPAkine CX546 (5 to 150μM). Both treatments triggered a concentration-dependent increase in proliferation, evaluated in 48h treated cultures through the BrdU incorporation assay. AMPA and AMPAkines stimulated neuronal differentiation as the numbers of NeuN mature neurons increased in 7 days treated cultures. Moreover AMPA and AMPAkine treatments increased the numbers of functional neurons, evaluated by single cell calcium imaging. Immunoassays for the phosphorylated form of the JNK signaling were also performed in SVZ cell cultures treated with AMPA 1μM and AMPAKine CX546 5μM for 6h. AMPA and AMPAkine treatment promoted a five and six fold increase in the number and in the total length of the ramifications per neurosphere, respectively. Knowing that JNK signaling is involved in axonogenesis, these data show that AMPA and AMPAkine CX 546 improve neuronal maturation.
Altogether, these data demonstrate that AMPA and AMPAkines CX 546 are positive modulators of neurogenesis in SVZ cell cultures and highlight the possible use of AMPAkines for future development of cell- based brain therapies.
Acknowledgments: Convenio GRICES-CAPES and Fundacao para a Ciencia e Tecnologia: PTDC-SAU-NEU- 68465-2006
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Abstracts
Citation:
De-Sampaio-Schitine
C
(2009). AMPA and ampakines as proneurogenic modulators of progenitors derived from subventricular zone.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.037
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
06 Aug 2009;
Published Online:
06 Aug 2009.
*
Correspondence:
Clarissa De-Sampaio-Schitine, Universidade de Coimbra, Centro de Neurociencias e Biologia Celular, Alicante, Portugal, schitine@biof.ufrj.br