Overexpression of APP provides neuroprotection in the absence of functional benefit following middle cerebral artery occlusion in rats

被引:46
作者
Clarke, Jared
Thornell, Anders
Corbett, Dale
Soininen, Hilkka
Hiltunen, Mikko
Jolkkonen, Jukka [1 ]
机构
[1] Univ Kuopio, Dept Neurol, FIN-70211 Kuopio, Finland
[2] Mem Univ Newfoundland, Fac Med, St John, NF, Canada
[3] Swedish Univ Agr Sci, Uppsala, Sweden
[4] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland
关键词
amyloid; APP transgenic rats; behaviour; cerebral ischaemia; learning; stroke;
D O I
10.1111/j.1460-9568.2007.05807.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Cerebral ischaemia leads to a transient accumulation of beta-amyloid precursor protein (APP) and beta-amyloid (A beta) peptides adjacent to the ischaemic lesion. There is conflicting evidence that APP/A beta fragments may either enhance neuronal plasticity or be neurotoxic. The aim of the current study was to assess the effect of overexpression of human APP in rats on functional recovery following cerebral ischaemia. Adult APP-overexpressing (hAPP695 Tg) rats subjected to transient middle cerebral artery occlusion (MCAO) had significantly smaller infarct volumes than non-transgenic littermates, yet did not perform better on a series of sensorimotor or learning tests during a 6-month follow-up period. In fact, transgenic animals were found to be significantly more impaired in both the beam-walking and Morris water maze tests following MCAO. Immunohistochemistry showed human A beta-positive staining in the cortex and hippocampus of APP transgenic rats. The present data suggest that while overexpression of APP in rats may provide some histological neuroprotection in the event of cerebral ischaemia, this does not translate into significant functional recovery.
引用
收藏
页码:1845 / 1852
页数:8
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