| First Author | Duffy AM | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 1 | Pages | 134-48 |
| PubMed ID | 25109765 | Mgi Jnum | J:218323 |
| Mgi Id | MGI:5617300 | Doi | 10.1016/j.neurobiolaging.2014.07.001 |
| Citation | Duffy AM, et al. (2015) Entorhinal cortical defects in Tg2576 mice are present as early as 2-4 months of age. Neurobiol Aging 36(1):134-48 |
| abstractText | The entorhinal cortex (EC) is one of the first brain areas to display neuropathology in Alzheimer's disease. A mouse model which simulates amyloid-beta (Abeta) neuropathology, the Tg2576 mouse, was used to address these early changes. Here, we show EC abnormalities occur in 2- to 4-month-old Tg2576 mice, an age before Abeta deposition and where previous studies suggest that there are few behavioral impairments. First we show, using a sandwich enzyme-linked immunosorbent assay, that soluble human Abeta40 and Abeta42 are detectable in the EC of 2-month-old Tg2576 mice before Abeta deposition. We then demonstrate that 2- to 4-month-old Tg2576 mice are impaired at object placement, an EC-dependent cognitive task. Next, we show that defects in neuronal nuclear antigen expression and myelin uptake occur in the superficial layers of the EC in 2- to 4-month-old Tg2576 mice. In slices from Tg2576 mice that contained the EC, there were repetitive field potentials evoked by a single stimulus to the underlying white matter, and a greater response to reduced extracellular magnesium ([Mg(2+)]o), suggesting increased excitability. However, deep layer neurons in Tg2576 mice had longer latencies to antidromic activation than wild type mice. The results show changes in the EC at early ages and suggest that altered excitability occurs before extensive plaque pathology. |
