Beta-amyloid peptides stimulate endozepine biosynthesis in cultured rat astrocytes

Tursonjan Tokay (1, 2) , Olfa Masmoudi (1, 2) , Pierrick Gandolfo (1, 2) , Jérôme Leprince (1, 2) , Georges Pelletier (3) , Hubert Vaudry (1, 2) , Marie-Christine Tonon (1, 2)

1 Neuroendocrinologie cellulaire et moléculaire
2 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
3 Laval University Medical center

Accumulation of beta-amyloid peptide (Abeta), which is a landmark of Alzheimer's disease, may alter astrocyte functions before any visible symptoms of the disease occur. Here, we examined the effects of Abeta on biosynthesis and release of diazepam-binding inhibitor (DBI), a polypeptide primarily expressed by astroglial cells in the CNS. Quantitative RT-PCR and specific radioimmunoassay demonstrated that aggregated Abeta(25-35), at concentrations up to 10(-4) m, induced a dose-dependent increase in DBI mRNA expression and DBI-related peptide release from cultured rat astrocytes. These effects were totally suppressed when aggregation of Abeta(25-35) was prevented by Congo red. Measurement of the number of living cells revealed that Abeta(25-35) induced a trophic rather than a toxic effect on astrocytes. Administration of cycloheximide blocked Abeta(25-35)-induced increase of DBI gene expression and endozepine accumulation in astrocytes, indicating that protein synthesis is required for DBI gene expression. Altogether, the present data suggest that Abeta-induced activation of endozepine biosynthesis and release may contribute to astrocyte proliferation associated with Alzheimer's disease.

Domaines: Chimie thérapeutique; Interactions cellulaires [q-bio.CB]; Neurobiologie; Pharmacologie

Tursonjan Tokay, Olfa Masmoudi, Pierrick Gandolfo, Jérôme Leprince, Georges Pelletier, et al.. Beta-amyloid peptides stimulate endozepine biosynthesis in cultured rat astrocytes. Journal of Neurochemistry, 2005, 94 (3), pp.607-616. ⟨10.1111/j.1471-4159.2005.03102.x⟩. ⟨hal-01974260⟩