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Protein targeting to glycogen mRNA expression is stimulated by noradrenaline in mouse cortical astrocytes
Author(s) -
Allaman Igor,
Pellerin Luc,
Magistretti Pierre J.
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(200006)30:4<382::aid-glia70>3.0.co;2-0
Subject(s) - biology , glycogen , endocrinology , glycogen synthase , medicine , forskolin , activator (genetics) , astrocyte , vasoactive intestinal peptide , signal transduction , receptor , microbiology and biotechnology , biochemistry , central nervous system , neuropeptide , stimulation
Brain glycogen levels are dynamically regulated by certain neurotransmitters, including noradrenaline (NA) and vasoactive intestinal peptide (VIP). In particular, glycogen synthesis involves activation by NA and VIP of the transcription factors C/EBPβ and ‐δ as well as the induction of glycogen synthase. Glycogen accumulation is found in a variety of neuropathological conditions, including reactive astrocytosis after CNS lesions, as well as in Alzheimer's disease. Protein targeting to glycogen (PTG) belongs to a family of proteins that play a key role in glycogen synthesis in peripheral tissues. In this study, we report the presence of PTG mRNA in adult mouse brain, as well as in astrocytes, a non‐neuronal cell type that contains most of brain glycogen. Using primary cultures of mouse cortical astrocytes, we observed that NA leads to time‐ and concentration‐dependent induction of PTG mRNA expression. This effect, concomitant to an enhancement of glycogen synthesis in these cells, depends on the activation of β 1 ‐adrenergic receptors. Induction of PTG mRNA expression was mimicked by the adenylate cyclase activator forskolin and by dibutyryl cAMP, suggesting the involvement of the cAMP‐dependent signal transduction cascade. Among other neuroactive substances known to elevate glycogen levels in astrocytes, VIP had a comparable effect to that of noradrenaline, whereas insulin and glutamate were without effect on PTG mRNA expression. These data suggest that increased PTG expression by neurotransmitters such as noradrenaline and VIP could represent a major event leading to enhancement of glycogen levels in astrocytes. GLIA 30:382–391, 2000. © 2000 Wiley‐Liss, Inc.