beta-Amyloid peptide-induced morphological changes coincide with increased K+ and Cl- channel activity in rat cortical astrocytes.
Alzheimer's disease (AD) is a slowly progressing neurodegenerative disease characterized by the loss of neurons and formation of amyloid plaques, often surrounded by reactive astrocytes. Astrocytes are important regulators of the normal neuronal environment, and changed astrocyte function may lead to increased neuronal vulnerability. The slow onset of the disease with a gradual increase in the beta-amyloid peptide (beta-AP) concentrations may alter astrocyte function long before any visible symptoms of the disease are observed. We, therefore, studied in vitro the effects of small amounts of beta-AP(1-40) and -(25-35) on rat cortical astrocyte function observing changes in cell morphology, intracellular calcium levels (Cai), and ion channel activity. Incubation with 10 and 200 nM beta-APs caused increased process formation and hypertrophy. Stellation was also detected when astrocyte cultures were incubated with 1 microM AlCl3 alone, or together with beta-APs. Fura-2AM-loaded astrocytes were used to test whether the morphological changes were connected to changes in Cai levels. 1 microM beta-AP(1-40) induced transient Cai increase in approximately 17%, and beta-AP(25-35) in approximately 36% of astrocytes. In patch-clamp studies, increased K+ and Cl- channel activity was detected with 10-100 nM beta-AP(1-40). With large amounts (20 microM) of beta-AP(1-40), an additional giant channel activity emerged. These beta-AP-induced changes in astrocyte function may eventually be critical for the neuronal survival in Alzheimer's disease.
Jalonen
T O
TO
Division of Neurosurgery, Albany Medical College, NY 12208, USA. tuula-jalonen@ccgateway.amc.edu
Charniga
C J
CJ
Wielt
D B
DB
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry* / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D008297:Male; D008855:Microscopy, Electron, Scanning; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D018118:Chloride Channels; D015221:Potassium Channels; D002118:Calcium