GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone

Valerio Magnaghi, A. Párducz, Angelisa Frasca, Marinella Ballabio, Patrizia Procacci, Giorgio Racagni, Giambattista Bonanno, Fabio Fumagalli

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Recent evidence showed that neurotransmitters are synthesised in glial cells, such as the Schwann cells, which form myelin sheaths in the PNS. While the presence of GABA type A (GABA-A) receptors has been previously demonstrated in these cells, the evidence of GABA synthesis remained still elusive. In an attempt to demonstrate the presence of GABA in rat Schwann cells, we adopted a strategy, using several integrated neurochemical, molecular as well as immunocytochemical approaches. We first demonstrated the presence of glutamic acid decarboxylase of 67 kDa (GAD67) in Schwann cells, a crucial enzyme of the GABA synthesis mechanism. Second, we demonstrated that GABA is synthesized and localized in Schwann cells. As the third step we showed that allopregnanolone (10 nM), a potent allosteric modulator of GABA-A receptors, stimulates GABA synthesis through increased levels of GAD67 in Schwann cells. Analysis of intracellular signalling mechanisms revealed that the protein kinase A pathway, through enhanced cAMP levels and cAMP response element binding protein phosphorylation, modulates the allosteric action of allopregnanolone at the GABA-A receptor in Schwann cells. Our findings are the first to demonstrate that this GABA mechanism is active in Schwann cells thus establishing new potential therapeutic targets to control Schwann cell biology, which may prove useful in the treatment of several neurodegenerative disorders.

Original languageEnglish
Pages (from-to)980-990
Number of pages11
JournalJournal of Neurochemistry
Volume112
Issue number4
DOIs
Publication statusPublished - Feb 2010

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Pregnanolone
Schwann Cells
gamma-Aminobutyric Acid
Steroids
Cells
GABA-A Receptors
Glutamate Decarboxylase
Cytology
Cyclic AMP Response Element-Binding Protein
Phosphorylation
Cyclic AMP-Dependent Protein Kinases
Modulators
Myelin Sheath
Neurotransmitter Agents
Rats
Neuroglia
Neurodegenerative Diseases
Cell Biology
Enzymes

Keywords

  • cAMP response element binding protein
  • Glutamic acid decarboxylase
  • Myelin
  • Neuron-glia interaction
  • Tetrahydroprogesterone

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone. / Magnaghi, Valerio; Párducz, A.; Frasca, Angelisa; Ballabio, Marinella; Procacci, Patrizia; Racagni, Giorgio; Bonanno, Giambattista; Fumagalli, Fabio.

In: Journal of Neurochemistry, Vol. 112, No. 4, 02.2010, p. 980-990.

Research output: Contribution to journalArticle

Magnaghi, V, Párducz, A, Frasca, A, Ballabio, M, Procacci, P, Racagni, G, Bonanno, G & Fumagalli, F 2010, 'GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone', Journal of Neurochemistry, vol. 112, no. 4, pp. 980-990. https://doi.org/10.1111/j.1471-4159.2009.06512.x
Magnaghi, Valerio ; Párducz, A. ; Frasca, Angelisa ; Ballabio, Marinella ; Procacci, Patrizia ; Racagni, Giorgio ; Bonanno, Giambattista ; Fumagalli, Fabio. / GABA synthesis in Schwann cells is induced by the neuroactive steroid allopregnanolone. In: Journal of Neurochemistry. 2010 ; Vol. 112, No. 4. pp. 980-990.
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