Abstract
BackgroundNeurons display a highly polarized architecture. Their ability to modify their features under intracellular and extracellular stimuli, known as synaptic plasticity, is a key component of the neurochemical basis of learning and memory. A key feature of synaptic plasticity involves the delivery of mRNAs to distinct sub-cellular domains where they are locally translated. Regulatory coordination of these spatio-temporal events is critical for synaptogenesis and synaptic plasticity as defects in these processes can lead to neurological diseases. In this work, using microdissected dendrites from primary cultures of hippocampal neurons of two mouse strains (C57BL/6 and Balb/c) and one rat strain (Sprague–Dawley), we investigate via microarrays, subcellular localization of mRNAs in dendrites of neurons to assay the evolutionary differences in subcellular dendritic transcripts localization.ResultsOur microarray analysis highlighted significantly greater evolutionary diversification of RNA localization in the dendritic transcriptomes (81% gene identity difference among the top 5% highly expressed genes) compared to the transcriptomes of 11 different central nervous system (CNS) and non-CNS tissues (average of 44% gene identity difference among the top 5% highly expressed genes). Differentially localized genes include many genes involved in CNS function.ConclusionsSpecies differences in sub-cellular localization may reflect non-functional neutral drift. However, the functional categories of mRNA showing differential localization suggest that at least part of the divergence may reflect activity-dependent functional differences of neurons, mediated by species-specific RNA subcellular localization mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-883) contains supplementary material, which is available to authorized users.
Highlights
Recent studies have shown that hundreds or even thousands of different mRNA are found in the dendrites of neurons [18,23]; in this study, we hypothesized that the evolution of rodent brains may involve divergences in general gene expression and changes in the levels of dendritic localization of mRNA within individual neurons
Microarray analysis shows a high degree of divergence between mouse and rat dendritic transcriptomes To assess neuronal dendrite expression divergence between mice and rats, we used the Affymetrix array platform to assay the transcriptomes of micro-dissected individual dendrites of hippocampal neurons in dispersed primary cell cultures from Sprague–Dawley rat (9 biological replicates), C57BL/6 mouse (14 biological replicates), and Balb/c mouse (5 biological replicates)
Our sample collections typically have 5% axonal RNA (~20 neurites collected per cell) but preponderance of the RNA is expected to be derived from the dendrites and we will use the term dendritic transcriptome with this caveat
Summary
A key feature of synaptic plasticity involves the delivery of mRNAs to distinct sub-cellular domains where they are locally translated. Regulatory coordination of these spatio-temporal events is critical for synaptogenesis and synaptic plasticity as defects in these processes can lead to neurological diseases. As in any organismal tissue, changes in serious effects at the cellular and organismal level, leading to neurological diseases such as Fragile X Syndrome, Spinal Muscular Atrophy, autism, among others [19,20,21,22] These and many other studies clearly show that dendritic localization of mRNA is critical to CNS function. Our results suggest that brain evolution between closely related species might involve anatomical differences at the morphological level and RNA-mediated subcellular differences in synaptic compartments of individual neurons
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