Open AccessReversal of aging‐related emotional memory deficits by norepinephrine via regulating the stability of surface AMPA receptors
Author(s) -
Luo Yi,
Zhou Jun,
Li MingXing,
Wu PengFei,
Hu ZhuangLi,
Ni Lan,
Jin You,
Chen JianGuo,
Wang Fang
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12282
Subject(s) - long term potentiation , ampa receptor , desipramine , hippocampus , synaptic plasticity , neuroscience , downregulation and upregulation , hippocampal formation , receptor , biology , psychology , glutamate receptor , medicine , antidepressant , gene , biochemistry
Summary Aging‐related emotional memory deficit is a well‐known complication in A lzheimer's disease and normal aging. However, little is known about its molecular mechanism. To address this issue, we examined the role of norepinephrine ( NE ) and its relevant drug desipramine in the regulation of hippocampal long‐term potentiation ( LTP ), surface expression of AMPA receptor, and associative fear memory in rats. We found that there was a defective regulation of NE content and AMPA receptor trafficking during fear conditioning, which were accompanied by impaired emotional memory and LTP in aged rats. Furthermore, we also found that the exogenous upregulation of NE ameliorated the impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in aged rats, and the downregulation of NE impaired LTP in adult rats. Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats. These results imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging rats and suggest that desipramine is a potential candidate for treating aging‐related emotional memory deficit.