Abstract：
:Deficits in synaptic structure and function are likely to underlie cognitive impairments in Alzheimer's disease. While synaptic deficits are commonly found in animal models of amyloidosis, it is unclear how amyloid pathology may impair synaptic functions. In some amyloid mouse models of Alzheimer's disease, however, synaptic deficits are preceded by hyperexcitability of glutamate synapses. In the amyloid transgenic mouse model TgCRND8, we therefore investigated whether early enhancement of glutamatergic transmission was responsible for development of later synaptic deficits. Hippocampi from 1-month-old TgCRND8 mice revealed increased basal transmission and plasticity of glutamate synapses that was related to increased levels of tumor necrosis factor α (TNFα). Treating these 1-month-old mice for 4 weeks with the TNFα inhibitor XPro1595 prevented synaptic deficits otherwise apparent at the age of 6 months. In this mouse model at least, reversing the hyperexcitability of glutamate synapses via TNFα blockade before the onset of amyloid plaque formation prevented later synaptic deficits.
journal_name
Neurobiol Agingjournal_title
Neurobiology of agingauthors
Cavanagh C,Tse YC,Nguyen HB,Krantic S,Breitner JC,Quirion R,Wong TPdoi
10.1016/j.neurobiolaging.2016.07.009subject
Has Abstractpub_date
2016-11-01 00:00:00pages
41-49eissn
0197-4580issn
1558-1497pii
S0197-4580(16)30139-7journal_volume
47pub_type
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