Polyphosphoinositide Metabolism and Golgi Complex Morphology in Hippocampal Neurons in Primary Culture is Altered by Chronic Ethanol Exposure

Esteban-Pretel, Guillermo; Marín, M. Luisa; Romero, Ana; Timoneda, Joaquín; Ponsoda, Xavier; Ballestín, Raúl; Renau‐Piqueras, Jaime

doi:10.1093/alcalc/ags117

Alcohol and Alcoholism

2012

DOI: 10.1093/alcalc/ags117

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Polyphosphoinositide Metabolism and Golgi Complex Morphology in Hippocampal Neurons in Primary Culture is Altered by Chronic Ethanol Exposure

Guillermo Esteban-Pretel¹,

M. Luisa Marín²,

Ana Romero³

et al.

Abstract: The deregulation of the metabolism of PtdIns may underlie the ethanol-induced alterations on different neuronal processes, including intracellular trafficking and cytoskeletal integrity.

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Cited by 4 publications

References 110 publications

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Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture

Romero¹,

Renau‐Piqueras²,

Marín³

et al. 2013

Neurotox Res

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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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Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture

Romero¹,

Renau‐Piqueras²,

Marín³

et al. 2013

Neurotox Res

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Chronic Alcohol Exposure Affects the Cell Components Involved in Membrane Traffic in Neuronal Dendrites

et al. 2014

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The specific traffic of the membrane components in neurons is a major requirement to establish and maintain neuronal domains-the axonal and the somatodendritic domains-and their polarized morphology. Unlike axons, dendrites contain membranous organelles, which are involved in the secretory pathway, including the endoplasmic reticulum, the Golgi apparatus and post-Golgi apparatus carriers, the cytoskeleton, and plasma membrane. A variety of molecules and factors are also involved in this process. Previous studies have shown that chronic alcohol exposure negatively affects several of these cell components, such as the Golgi apparatus or cytoskeleton in neurons. Yet very little information is available on the possible effects of this exposure on the remaining cell elements involved in intracellular trafficking in neurons, particularly in dendrites. By qualitative and quantitative electron microscopy, immunofluorescence and immunoblotting, we herein show that chronic exposure to moderate levels (30 mM) of ethanol in cultured neurons reduces the volume and surface density of the rough endoplasmic reticulum, and increases the levels of GRP78, a chaperone involved in endoplasmic reticulum stress. Ethanol also significantly diminishes the proportion of neurons that show an extension of Golgi into dendrites and dendritic Golgi outposts, a structure present exclusively in longer, thicker apical dendrites. Both Golgi apparatus types were also fragmented into a large number of cells. We also investigated the effect of alcohol on the levels of microtubule-based motor proteins KIF5, KIF17, KIFC2, dynein, and myosin IIb, responsible for transporting different cargoes in dendrites. Of these, alcohol differently affects several of them by lowering dynein and raising KIF5, KIFC2, and myosin IIb. These results, together with other previously published ones, suggest that practically all the protein trafficking steps in dendrites are altered to a greater or lesser extent by chronic alcohol exposure in neuronal cells, which may have negative repercussions for the development and maintenance of their polarized morphology and function.

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Modification of Erythrocyte Membrane Proteins, Enzymes and Transport Mechanisms in Chronic Alcoholics: An In vivo and In vitro Study

Maturu¹,

Reddy

Padmavathi

et al. 2013

Alcohol and Alcoholism

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Polyphosphoinositide Metabolism and Golgi Complex Morphology in Hippocampal Neurons in Primary Culture is Altered by Chronic Ethanol Exposure

Abstract: The deregulation of the metabolism of PtdIns may underlie the ethanol-induced alterations on different neuronal processes, including intracellular trafficking and cytoskeletal integrity.

Cited by 4 publications

References 110 publications

Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture

Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture

Chronic Alcohol Exposure Affects the Cell Components Involved in Membrane Traffic in Neuronal Dendrites

Modification of Erythrocyte Membrane Proteins, Enzymes and Transport Mechanisms in Chronic Alcoholics: An In vivo and In vitro Study

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