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Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1.
- Source :
- Journal of Neuroscience; 10/19/2016, Vol. 36 Issue 42, p10843-10852, 10p
- Publication Year :
- 2016
-
Abstract
- Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECII<subscript>PN</subscript>) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1<subscript>PV</subscript>) and undergo selective degeneration in the early stages of Alzheimer's disease (AD). Here, we show that death-associated protein kinase 1 (DAPK1) is selectively activated in ECII<subscript>PN</subscript> of AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECII<subscript>PN</subscript>-CA1<subscript>PV</subscript> synaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECII<subscript>PN</subscript> contributes to a memory loss in AD and hence warrants a promising target for the treatment of AD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02706474
- Volume :
- 36
- Issue :
- 42
- Database :
- Complementary Index
- Journal :
- Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 119037544
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.2258-16.2016