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Monoamine neurotransmitters modulate NT-3 levels in astrocytes

Background

Neurotrophin-3 (NT-3), a member of the neurotrophin family of neurotrophic factors, displays profound neuromodulatory functions in the normal and in the diseased brain. Under physiological conditions, NT-3 is produced by neuronal cells and also by local glial cells. We focused our investigation on the ability of astrocytes to synthesize NT-3 and, additionally, on the active involvement of the neurotransmitters noradrenaline, adrenaline, dopamine, histamine and serotonin (5-HT) in the regulation of NT-3 production in neonatal rat cortical astrocytes.

Results

Our study confirms the ability of neonatal rat cortical and cerebellar astrocytes in primary culture to express and synthesize significant amounts of NT-3. The examined monoamines, with the exception of 5-HT are able to potently and transiently increase NT-3 mRNA and NT-3 protein cell levels; their action is dose- and time-dependent. Screening different activators of basic intracellular second messenger systems which can participate in the possible monoamine receptor mediated stimulation of NT-3 by examined monoamines revealed that forskolin, dibutyryl cAMP (dBcAMP), as well as calcimycin (Ca2+ ionophore A23187) and phorbol 12-myristate 13-acetate (TPA), markedly increase the cellular level of NT-3 protein. Neurotransmitter-induced NT-3 is susceptible (to varying degrees) to inhibition by H-89 (an inhibitor of protein kinase A, PKA) or staurosporin (an inhibitor of protein kinase C, PKC), which led us to conclude that downstream signaling responsible for the stimulation of NT-3 synthesis by monoamines in astrocytes is a receptor-mediated process consisting of multiple, complex intracellular mechanisms involving the cAMP/PKA pathway, activation of PKC, as well as mobilization of Ca2+ ions.

Conclusion

In conclusion, our study indicates for the first time that monoaminergic neurotransmitters play an important role in the regulation of neurotropic NT-3 activity in cultured rat astrocytes.

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Correspondence to Damijana M Jurič.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Jurič, D.M. Monoamine neurotransmitters modulate NT-3 levels in astrocytes. BMC Pharmacol 9, A60 (2009). https://doi.org/10.1186/1471-2210-9-S2-A60

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Keywords

  • Monoamine
  • Cortical Astrocyte
  • Monoamine Neurotransmitter
  • Dibutyryl cAMP
  • Monoaminergic Neurotransmitter