| First Author | Zhang D | Year | 2010 |
| Journal | J Neurochem | Volume | 115 |
| Issue | 5 | Pages | 1215-21 |
| PubMed ID | 20854432 | Mgi Jnum | J:166955 |
| Mgi Id | MGI:4850236 | Doi | 10.1111/j.1471-4159.2010.07011.x |
| Citation | Zhang D, et al. (2010) Inactivation of presenilins causes pre-synaptic impairment prior to post-synaptic dysfunction. J Neurochem 115(5):1215-21 |
| abstractText | J. Neurochem. (2010) 115, 1215-1221. ABSTRACT: Synaptic dysfunction is widely thought to be a pathogenic precursor to neurodegeneration in Alzheimer's disease (AD), and the extent of synaptic loss provides the best correlate for the severity of dementia in AD patients. Presenilins 1 and 2 are the major causative genes of early-onset familial AD. Conditional inactivation of presenilins in the adult cerebral cortex results in synaptic dysfunction and memory impairment, followed by age-dependent neurodegeneration. To characterize further the consequence of presenilin inactivation in the synapse, we evaluated the temporal development of pre-synaptic and post-synaptic deficits in the Schaeffer-collateral pathway of presenilin conditional double knockout (PS cDKO) mice prior to onset of neurodegeneration. Following presenilin inactivation at 4 weeks, synaptic facilitation and probability of neurotransmitter release are impaired in PS cDKO mice at 5 weeks of age, whereas post-synaptic NMDA receptor (NMDAR)-mediated responses are normal at 5 weeks but impaired at 6 weeks of age. Long-term potentiation induced by theta burst stimulation is also reduced in PS cDKO mice at 6 weeks of age. These results show that loss of presenilins results in pre-synaptic deficits in short-term plasticity and probability of neurotransmitter release prior to post-synaptic NMDAR dysfunction, raising the possibility that presenilins may regulate post-synaptic NMDAR function in part via a trans-synaptic mechanism. |
