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Heterogeneity in Synaptogenic Profile of Astrocytes from Different Brain Regions

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Abstract

Astrocytes, the most abundant glial cells in the central nervous system (CNS), comprise a heterogeneous population of cells. However, how this heterogeneity impacts their function within brain homeostasis and response to injury and disease is still largely unknown. Recently, astrocytes have been recognized as important regulators of synapse formation and maturation. Here, we analyzed the synaptogenic property of astrocytes from different regions of the CNS. The effect of conditioned medium derived from astrocytes (astrocyte-conditioned medium (ACM)) from cerebral cortex, hippocampus, midbrain and cerebellum, in synapse formation, was evaluated. Synapse formation was analyzed by quantification of pre- and postsynaptic proteins, synaptophysin, and postsynaptic density protein 95 (PSD-95). ACM from the four regions increased significantly the number of synaptophysin/PSD-95 puncta on neurons from the same and different brain regions. Differences on astrocytic synaptogenic potential between the regions were observed according to ACM protein concentration. Thus, cerebellar astrocytes have higher synaptogenic effect when ACM is less concentrated. Also, heterotypical co-culture assays revealed that neurons from cerebral cortex and midbrain equally respond to ACM, indicating that differences in synapse effect are unlike to be neuron-autonomous. The expression profile of the synaptogenic molecules secreted by astrocytes from distinct brain regions was analyzed by qPCR. Gene expression of glypicans 4 and 6, hevin, and secreted protein-acidic and rich in cysteine (SPARC) greatly varies between astrocytes from different brain regions. Furthermore, in vivo analysis of hevin protein confirmed that variance. These findings highlight the heterogeneity of astrocytes and suggest that their synaptogenic potential may be different in each brain region, mainly due to distinct gene expression profiles.

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Acknowledgements

We thank Marcelo Meloni and Grasiela Ventura for technical assistance. This work was supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Ministério da Saúde, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).

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  1. Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, 21941-902, Brazil

    Andrea Schmidt Buosi, Isadora Matias, Ana Paula Bergamo Araujo, Carolina Batista & Flávia Carvalho Alcantara Gomes

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  1. Andrea Schmidt Buosi
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  2. Isadora Matias
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Correspondence to Flávia Carvalho Alcantara Gomes.

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Fig S1

ACM synaptogenic property has a protein nature. Neuronal cultures with 12 DIV from cerebral cortex were treated for 3 h with DMEM/F12 (control), with cortex ACM and with boiled cortex ACM (boiled for 5 min). Excitatory synapse formation was analyzed by quantification of synaptic proteins puncta numbers. (n = 3). ***P < 0.001. (GIF 17 kb)

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Buosi, A.S., Matias, I., Araujo, A.P.B. et al. Heterogeneity in Synaptogenic Profile of Astrocytes from Different Brain Regions. Mol Neurobiol 55, 751–762 (2018). https://doi.org/10.1007/s12035-016-0343-z

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