Progesterone-induced agrin expression in astrocytes modulates glia-neuron interactions leading to synapse formation.

Full Abstract

Experimental evidence recently obtained suggests that synaptogenesis is a tripartite event in which not only pre- and post-synaptic neurons but also glial cells play a key role. However, the molecular mechanisms by which glia modulate the formation of synapses in the CNS remain poorly understood. In the present study, we analyzed the role of astrocytes in synapse formation in cultured hippocampal rat neurons. For these experiments, hippocampal neurons were cultured in the presence or absence of a monolayer of astrocytes. Our results indicated that hippocampal neurons cultured in the presence of astrocytes formed more synapses than the ones cultured in their absence only when kept in N2 serum-free medium. To get insights into the potential molecular mechanisms underlying this effect, we analyzed the expression of proteins known to induce synapse formation in hippocampal neurons. A significant increase in agrin expression was detected in astrocytes cultured in N2 serum-free medium when compared with the ones cultured in serum containing medium. Experiments performed using different components of the N2 mixture indicated that progesterone induced the expression of agrin in astrocytes. Taken collectively, these results provide evidence supporting a role for astrocytes in synapse formation in central neurons. Furthermore, they identified agrin as a potential mediator of this effect, and astrocytes as a bridge between the endocrine and nervous systems during synaptogenesis.

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Author information

Author/s: Tournell, C E (CE); Bergstrom, R A (RA); Ferreira, A (A);

Affiliation: Department of Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Grants: NS046834 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: Neuroscience (Neuroscience), published in United States. (Language: eng)

Reference: 2006-Sep; vol 141 (issue 3) : pp 1327-38

Dates: Created 2006/08/04; Completed 2006/10/18; Revised 2007/11/15;

PMID: 16777347, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - chemistry; genetics; metabolism
Animals
Blotting, Western - methods
Cell Count - methods
Cells, Cultured
Cerebral Cortex - cytology
Coculture Techniques - methods
Culture Media, Conditioned - pharmacology
Drug Interactions
Embryo, Mammalian
Enzyme Inhibitors - pharmacology
Gene Expression - drug effects; physiology
Hippocampus - cytology

Hippocampus - cytology
Immunohistochemistry - methods
Intracellular Signaling Peptides and Proteins - metabolism
Membrane Proteins - metabolism
Mifepristone - pharmacology
Neuroglia - drug effects; physiology
Neurons - physiology
Oligodeoxyribonucleotides, Antisense - pharmacology
Progesterone - pharmacology
RNA, Messenger - metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction - methods
Synapses - physiology

Associated Chemicals: Agrin (0) ; Culture Media, Conditioned (0) ; Dlgh4 protein, rat (0) ; Enzyme Inhibitors (0) ; Intracellular Signaling Peptides and Proteins (0) ; Membrane Proteins (0) ; Oligodeoxyribonucleotides, Antisense (0) ; RNA, Messenger (0) ; Progesterone (57-83-0) ; Mifepristone (84371-65-3)

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