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P2‐447: Effect of APP5‐mer peptide and its analog P165 on proliferation and differationation of neural stem cells in rat brain
Author(s) -
Meng Yan,
Zhang Jingyan,
Zhao Zhiwei,
Ji Zhijuan,
Wang Hongjuan,
Wang Rong
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1526
Subject(s) - neurogenesis , neural stem cell , dentate gyrus , neurodegeneration , hippocampal formation , stem cell , biology , microbiology and biotechnology , hippocampus , in vivo , peptide , in vitro , chemistry , neuroscience , biochemistry , medicine , genetics , disease
teen healthy young male subjects participated in a randomised, double-blind, placebo-controlled, cross-over study. Subjects were scanned twice, once following placebo and once following GSK189254 (1 mg) administered orally. Subjects performed a paired associate learning task (PAL) and a visual delayed matching to sample task (DMTS) during scanning. The PAL involved repeated presentation of a set of patterns, allowing separate investigation of encoding, retrieval and learning. Imaging data were analysed with SPM5 and performance data with SPSS. Results: In the PAL task, encoding and retrieval elicited activation of networks incorporating lateral and medial frontal regions, and the posterior parietal lobes. GSK189254 did not modulate the signal in these networks. However, the amplitude of activation in a region between the mamillary bodies and posterior hypothalamus (consistent with the location of histaminergic neurons), showed a quasi-linear relationship with the order of repetition of each set of patterns, suggesting a regional effect of learning. GSK189254 significantly modified the slope of this relationship. Faster reaction times on GSK189254 correlated significantly with the amplitude of signal change in this region. In the DMTS task, GSK189254 was associated with increased activation at the parieto-occipital junction, especially for responses after a short delay (3 s) condition. The increase in activity due to GSK189254 was correlated with shorter response latency. Conclusions: GSK189254 may modulate learning via stimulation of histaminergic neurons. It may also enhance processing during delayed recall in episodic memory task via modulation of activity in the parieto-occipital junction which is involved in visuospatial attention. Both cognitive tasks are impaired in AD. These findings suggest possible mechanisms by which GSK189254 could enhance cognition in impaired populations.