Amyloid beta-protein impairs astrocyte-mediated differentiation of hippocampal neurons.
Embryonic rat hippocampal neurons were cultured on poly-D-lysine (PDL) or on cortical astrocytes, some of which had been pretreated for 24 h with amyloid beta-protein (beta-AP). Amino acid-induced currents were quantified. Membrane capacitance (Cm), as well as the amplitude and density of amino acid-evoked currents recorded in neurons cultured on untreated astrocytes were all statistically greater than those recorded in neurons grown on PDL. However, compared to untreated astrocytes, those treated with beta-AP led to significantly lower values in neurons for Cm and GABA, kainate- and NMDA-induced currents, while glycine-activated current values were not significantly different. Furthermore, beta-AP treatment abolished spontaneous Cac2+ fluctuations in astrocytes, which may account for their impaired ability to promote the expression of functional transmitter receptors in neurons.
Liu
Q Y
QY
Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Schaffner
A
A
Chang
Y H
YH
Maric
D
D
Barker
J L
JL
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004553:Electric Conductivity; D004622:Embryo, Mammalian; D005333:Fetus; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D007608:Kainic Acid; D005998:Glycine