| First Author | Brown JT | Year | 2011 |
| Journal | Neurobiol Aging | Volume | 32 |
| Issue | 11 | Pages | 2109.e1-14 |
| PubMed ID | 21794952 | Mgi Jnum | J:176687 |
| Mgi Id | MGI:5292438 | Doi | 10.1016/j.neurobiolaging.2011.05.025 |
| Citation | Brown JT, et al. (2011) Altered intrinsic neuronal excitability and reduced Na+ currents in a mouse model of Alzheimer's disease. Neurobiol Aging 32(11):2109.e1-2109.e14 |
| abstractText | Transgenic mice that overproduce beta-amyloid (Abeta) peptides can exhibit central nervous system network hyperactivity. Patch clamp measurements from CA1 pyramidal cells of PSAPP and wild type mice were employed to investigate if altered intrinsic excitability could contribute to such network hyperfunction. At approximately 10 months, when PSAPP mice have a substantial central nervous system Abeta load, resting potential and input resistance were genotype-independent. However, PSAPP mice exhibited a substantially more prominent action potential (AP) burst close to the onset of weak depolarizing current stimuli. The spike afterdepolarization (ADP) was also larger in PSAPP mice. The rate of rise, width and height of APs were reduced in PSAPP animals; AP threshold was unaltered. Voltage-clamp recordings from nucleated macropatches revealed that somatic Na(+) current density was depressed by approximately 50% in PSAPP mice. K(+) current density was unaltered. All genotype-related differences were absent in PSAPP mice aged 5-7 weeks which lack a substantial Abeta load. We conclude that intrinsic neuronal hyperexcitability and changes to AP waveforms may contribute to neurophysiological deficits that arise as a consequence of Abeta accumulation. |
