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Brief Communications

Aβ Inhibition of Ionic Conductance in Mouse Basal Forebrain Neurons Is Dependent upon the Cellular Prion Protein PrPC

Kwai Alier, Li Ma, Jing Yang, David Westaway and Jack H. Jhamandas
Journal of Neuroscience 9 November 2011, 31 (45) 16292-16297; DOI: https://doi.org/10.1523/JNEUROSCI.4367-11.2011
Kwai Alier
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Li Ma
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Jing Yang
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David Westaway
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Jack H. Jhamandas
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Abstract

Current therapies for Alzheimer's disease (AD) address a loss of cholinergic neurons, while accumulation of neurotoxic amyloid β (Aβ) peptide assemblies is thought central to molecular pathogenesis. Overlaps may exist between prionopathies and AD wherein Aβ oligomers bind to the cellular prion protein PrPC and inhibit synaptic plasticity in the hippocampus (Laurén et al., 2009). Here we applied oligomeric Aβ to neurons with different PrP (Prnp) gene dosage. Whole-cell recordings were obtained from dissociated neurons of the diagonal band of Broca (DBB), a cholinergic basal forebrain nucleus. In wild-type (wt) mice, Aβ1–42 evoked a concentration-dependent reduction of whole-cell outward currents in a voltage range between −30 and +30 mV; reduction occurred through a combined modulation of a suite of potassium conductances including the delayed rectifier (IK), the transient outward (IA), and the iberiotoxin-sensitive (calcium-activated potassium, IC) currents. Inhibition was not seen with Aβ42–1 peptide, while Aβ1–42-induced responses were reduced by application of anti-PrP antibody, attenuated in cells from Prnp0/+ hemizygotes, and absent in Prnp0/0 homozygotes. Similarly, amyloidogenic amylin peptide depressed DBB whole-cell currents in DBB cells from wt mice, but not Prnp0/0 homozygotes. While prior studies give broad support for a neuroprotective function for PrPC, our data define a latent pro-pathogenic role in the presence of amyloid assemblies.

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The Journal of Neuroscience: 31 (45)
Journal of Neuroscience
Vol. 31, Issue 45
9 Nov 2011
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Aβ Inhibition of Ionic Conductance in Mouse Basal Forebrain Neurons Is Dependent upon the Cellular Prion Protein PrPC
Kwai Alier, Li Ma, Jing Yang, David Westaway, Jack H. Jhamandas
Journal of Neuroscience 9 November 2011, 31 (45) 16292-16297; DOI: 10.1523/JNEUROSCI.4367-11.2011

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Aβ Inhibition of Ionic Conductance in Mouse Basal Forebrain Neurons Is Dependent upon the Cellular Prion Protein PrPC
Kwai Alier, Li Ma, Jing Yang, David Westaway, Jack H. Jhamandas
Journal of Neuroscience 9 November 2011, 31 (45) 16292-16297; DOI: 10.1523/JNEUROSCI.4367-11.2011
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