Accumulation of β-amyloid peptide (Aβ), 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 Aβ 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 Aβ25-35, 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 Aβ 25-35 was prevented by Congo red. Measurement of the number of living cells revealed that Aβ25-35 induced a trophic rather than a toxic effect on astrocytes. Administration of cycloheximide blocked Aβ25-35-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 Aβ-induced activation of endozepine biosynthesis and release may contribute to astrocyte proliferation associated with Alzheimer's disease.
- Diazepam-binding inhibitor
- β-amyloid protein
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience