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Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer's Disease via Activation of DAPK1
- Source :
- The Journal of Neuroscience. 36:10843-10852
- Publication Year :
- 2016
- Publisher :
- Society for Neuroscience, 2016.
-
Abstract
- Excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) form functional excitatory synapses with CA1 parvalbumin inhibitory neurons (CA1PV) 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 ECIIPNof AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PVsynaptic loss and improves spatial learning and memory in AD mice. This study demonstrates that activation of DAPK1 in ECIIPNcontributes to a memory loss in AD and hence warrants a promising target for the treatment of AD.SIGNIFICANCE STATEMENTOur recent study reported that excitatory pyramidal neurons in the entorhinal cortical layer II region (ECIIPN) target to CA1 parvalbumin-type inhibitory neurons (CA1PV) at a direct pathway and are one of the most vulnerable brain cells that are selectively degenerated in the early stage of Alzheimer's disease (AD). Our present study shows that death-associated protein kinase 1 (DAPK1) is selectively activated in ECIIPNof AD mice. Inhibition of DAPK1 by deleting a catalytic domain or a death domain of DAPK1 rescues the ECIIPN-CA1PVsynaptic loss and improves spatial learning and memory in the early stage of AD. These data not only demonstrate a crucial molecular event for synaptic degeneration but also provide a therapeutic target for the treatment of AD.
- Subjects :
- Male
0301 basic medicine
Mice, Transgenic
Disease
Degeneration (medical)
Motor Activity
Biology
Inhibitory postsynaptic potential
Activation, Metabolic
Mice
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Memory
Animals
Entorhinal Cortex
Humans
Direct pathway of movement
Maze Learning
Protein kinase A
CA1 Region, Hippocampal
Postural Balance
Research Articles
Death domain
Pyramidal Cells
General Neuroscience
Electrophysiological Phenomena
Death-Associated Protein Kinases
Parvalbumins
030104 developmental biology
Synapses
Excitatory postsynaptic potential
biology.protein
Neuroscience
030217 neurology & neurosurgery
Parvalbumin
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....063e4d678a1cbfe5651edeb76f1b95e4