Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile postnatal days 9 (P9), P15, P21, P27, adolescent (P35) and different adult ages P70, P140 and P280 of C57Bl6/J mice. Using a quantitative proteomics workflow we quantified 1560 proteins of which 696 showed statistically significant differences over time. Synaptic proteins generally showed increased levels during maturation, whereas proteins involved in protein synthesis generally decreased in abundance. In several cases, proteins from a single functional molecular entity, e.g., subunits of the NMDA receptor, showed differences in their temporal regulation, which may reflect specific synaptic development features of connectivity, strength and plasticity. SNARE proteins, Snap 29/47 and Stx 7/8/12, showed higher expression in immature animals. Finally, we evaluated the function of Cxadr that showed high expression levels at P9 and a fast decline in expression during neuronal development. Knock down of the expression of Cxadr in cultured primary mouse neurons revealed a significant decrease in synapse density.

Original languageEnglish
Pages (from-to)35456
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016

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Proteome
Synapses
Brain
Proteins
SNARE Proteins
Synaptic Membranes
Workflow
N-Methyl-D-Aspartate Receptors
Proteomics
Neurons

Keywords

  • Journal Article

Cite this

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title = "Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development",
abstract = "Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile postnatal days 9 (P9), P15, P21, P27, adolescent (P35) and different adult ages P70, P140 and P280 of C57Bl6/J mice. Using a quantitative proteomics workflow we quantified 1560 proteins of which 696 showed statistically significant differences over time. Synaptic proteins generally showed increased levels during maturation, whereas proteins involved in protein synthesis generally decreased in abundance. In several cases, proteins from a single functional molecular entity, e.g., subunits of the NMDA receptor, showed differences in their temporal regulation, which may reflect specific synaptic development features of connectivity, strength and plasticity. SNARE proteins, Snap 29/47 and Stx 7/8/12, showed higher expression in immature animals. Finally, we evaluated the function of Cxadr that showed high expression levels at P9 and a fast decline in expression during neuronal development. Knock down of the expression of Cxadr in cultured primary mouse neurons revealed a significant decrease in synapse density.",
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Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development. / Gonzalez-Lozano, Miguel A; Gebuis, Titia; Hassan, Chopie; van Kesteren, Ronald E; Smit, August B; Li, K.W.; van Nierop, P.; Klemmer, P.

In: Scientific Reports, Vol. 6, 2016, p. 35456.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Gebuis, Titia

AU - Hassan, Chopie

AU - van Kesteren, Ronald E

AU - Smit, August B

AU - Li, K.W.

AU - van Nierop, P.

AU - Klemmer, P.

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