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Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture

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Abstract

Dendritic spines are specialised membrane protrusions of neuronal dendrites that receive the majority of excitatory synaptic inputs. Abnormal changes in their density, size and morphology have been associated with various neurological and psychiatric disorders, including those deriving from drug addiction. Dendritic spine formation, morphology and synaptic functions are governed by the actin cytoskeleton. Previous in vivo studies have shown that ethanol alters the number and morphology of spines, although the mechanisms underlying these alterations remain unknown. It has also been described how chronic ethanol exposure affects the levels, assembly and cellular organisation of the actin cytoskeleton in hippocampal neurons in primary culture. Therefore, we hypothesised that the ethanol-induced alterations in the number and shape of dendritic spines are due to alterations in the mechanisms regulating actin cytoskeleton integrity. The results presented herein show that chronic exposure to moderate levels of alcohol (30 mM) during the first 2 weeks of culture reduces dendritic spine density and alters the proportion of the different morphologies of these structures in hippocampal neurons, which affects the formation of mature spines. Apparently, these effects are associated with an increase in the G-actin/F-actin ratio due to a reduction of the F-actin fraction, leading to changes in the levels of the different factors regulating the organisation of this cytoskeletal component. The data presented herein indicate that these effects occur between weeks 1 and 2 of culture, an important period in dendritic spines development. These changes may be related to the dysfunction in the memory and learning processes present in children prenatally exposed to ethanol.

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Acknowledgments

We are very grateful to I. Monserrat for her technical help, to H.L. Warburton for linguistic assistance, and to A. Fuentes for helping us with the figures.

Fundings

The Spanish Ministry of Science and Innovation (Ministeriode Ciencia e Innovación, grant SAF2008-00305); A.M.R. is the recipient of a fellowship from the Spanish Ministry of Education.

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  1. Sección de Biología y Patología Celular, Centro de Investigación, Hospital Universitario ‘‘La Fe’’, Avenida Campanar 21, 46009, Valencia, Spain

    Ana M. Romero, Jaime Renau-Piqueras, M. Pilar Marin & Guillermo Esteban-Pretel

  2. Departamento de Bioquímica y Biología Molecular, Universidad de Valencia, 46100, Valencia, Spain

    Joaquin Timoneda

  3. Departamento de Anatomía y Biología Celular, Facultad de Medicina, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Universidad de Cantabria-IFIMAV, 39011, Santander, Spain

    Maria T. Berciano & Miguel Lafarga

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  1. Ana M. Romero
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Correspondence to Guillermo Esteban-Pretel.

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Ana M. Romero and Jaime Renau-Piqueras contributed equally to this study.

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Romero, A.M., Renau-Piqueras, J., Pilar Marin, M. et al. Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture. Neurotox Res 24, 532–548 (2013). https://doi.org/10.1007/s12640-013-9409-0

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