Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism - PubMed (original) (raw)

Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism

Christopher A Chapleau et al. J Neurodev Disord. 2009 Sep.

Abstract

The process of axonal and dendritic development establishes the synaptic circuitry of the central nervous system (CNS) and is the result of interactions between intrinsic molecular factors and the external environment. One growth factor that has a compelling function in neuronal development is the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF participates in axonal and dendritic differentiation during embryonic stages of neuronal development, as well as in the formation and maturation of dendritic spines during postnatal development. Recent studies have also implicated vesicular trafficking of BDNF via secretory vesicles, and both secretory and endosomal trafficking of vesicles containing synaptic proteins, such as neurotransmitter and neurotrophin receptors, in the regulation of axonal and dendritic differentiation, and in dendritic spine morphogenesis. Several genes that are either mutated or deregulated in neurodevelopmental disorders associated with mental retardation have now been identified, and several mouse models of these disorders have been generated and characterized. Interestingly, abnormalities in dendritic and synaptic structure are consistently observed in human neurodevelopmental disorders associated with mental retardation, and in mouse models of these disorders as well. Abnormalities in dendritic and synaptic differentiation are thought to underlie altered synaptic function and network connectivity, thus contributing to the clinical outcome. Here, we review the roles of BDNF and vesicular trafficking in axonal and dendritic differentiation in the context of dendritic and axonal morphological impairments commonly observed in neurodevelopmental disorders associated with mental retardation.

Keywords: Autism; BDNF; Dendritic spine; Hippocampus; Mental retardation; Pyramidal neuron; Rett syndrome; Vesicle trafficking.

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Figures

Fig. 1

Fig. 1

The structure of dendritic spines of hippocampal pyramidal neurons. Using particle-mediated gene transfer (a.k.a. gene gun), organotypic slice cultures were transfected with cDNA coding for eYFP. Top panels: Laser-scanning confocal microscopy images of a pyramidal neuron in area CA1 are shown at different magnifications to illustrate the complexity of their dendritic arbor and the abundance of dendritic spines in secondary and tertiary branches. Bottom left panel: A maximum-intensity projection of _z-_stacks shows a dendritic segment studded with the most common spine morphologies, i.e. stubby, mushroom and thin. The cartoon illustrates the geometrical dimensions measured in individual spines to categorize them (adapted from Ref. 32). Bottom right panel: A mushroom dendritic spine (outlined in green) forms an asymmetric synapse with a single presynaptic terminal (outlined in red) in stratum radiatum of area CA1 in organotypic slice culture

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