| First Author | Ahmed T | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 2 | Pages | 730-9 |
| PubMed ID | 25443285 | Mgi Jnum | J:219518 |
| Mgi Id | MGI:5621098 | Doi | 10.1016/j.neurobiolaging.2014.09.015 |
| Citation | Ahmed T, et al. (2015) Rescue of impaired late-phase long-term depression in a tau transgenic mouse model. Neurobiol Aging 36(2):730-9 |
| abstractText | Cognitive decline, the hallmark of Alzheimer's disease, and accompanying neuropsychiatric symptoms share dysfunctions of synaptic processes as a common cellular pathomechanism. Long-term potentiation has proven to be a sensitive tool for the "diagnosis" of such synaptic dysfunctions. Much less, however, is known about how long-term depression (LTD), an alternative mechanism for the storage of memory, is affected by Alzheimer's disease progression. Here, we demonstrate that impaired late LTD (>3 hours) in THY-Tau22 mice can be rescued by either inhibition of glycogen synthase kinase-3 (GSK3beta) activity or by application of the protein-phosphatase 2A agonist selenate. In line with these findings, we observed increased phosphorylation of GSK3beta at Y216 and reduced total phosphatase activity in biochemical assays of hippocampal tissue of THY-Tau22 mice. Interestingly, LTD induction and pharmacologic inhibition of GSK3beta appeared to downregulate GSK3ss activity via a marked upregulation of phosphorylation at the inhibitory Ser9 residue. Our results point to alterations in phosphorylation and/or dephosphorylation homeostasis as key mechanisms underlying the deficits in LTD and hippocampus-dependent learning found in THY-Tau22 mice. |
