Expression of nicotinic receptors on primary cultures of rat astrocytes and up-regulation of the α7, α4 and β2 subunits in response to nanomolar concentrations of the β-amyloid peptide 1–42

Abstract

Neuronal nicotinic acetylcholine receptors (nAChRs) are thought to be involved in the pathogenesis of Alzheimer's disease (AD). Interestingly, in the brains of patients with this disease, losses of several subtypes of nAChRs on neurons have been reported, while an increase in α7 nAChRs was recently detected in the astrocytes. However, little is presently known about the expressions of individual subunits of nAChR on rat astrocytes in primary culture or the possible influence of exposure to β-amyloid peptide (Aβ), a neuropathological hallmark of AD, on this expression. Thus, in the present investigation the levels of individual nAChR subunits on primary rat astrocytes and the possible direct influence of Aβs on the receptors were examined by RT-PCR, Western blotting, monitoring intracellular free calcium and immunohistochemistry. The α4, α7, β2 and β3 subunits and related calcium channel responses were found in these cells, whereas neither α2 nor α3 could be detected. Elevation in the levels of α7, α4 and β2 mRNAs and proteins were observed in astrocytes exposed to 0.1–100 nM Aβ 1–42. In contrast, incubation with 1 μM Aβ 1–42 or Aβ 35–25 did not affect these levels. We propose that the enhanced expression of α7, α4 and β2 nAChRs by astrocytes stimulated directly by nanomolar concentrations of Aβ 1–42 might be related to ongoing defensive or compensative mechanisms.