Pugh Perdita L, Richardson Jill C, Bate Simon T, Upton Neil, Sunter David
Neurology & GI CEDD, GlaxoSmithKline Research and Development Limited, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
Behav Brain Res. 2007 Mar 12;178(1):18-28. doi: 10.1016/j.bbr.2006.11.044. Epub 2007 Jan 16.
Alzheimer's disease (AD) is characterised by progressive cognitive impairment with neuropsychiatric symptoms such as anomalous motor behaviour, depression, anxiety, weight loss, irritability and agitation. The effect of hAPP and PS1 overexpression on cognition has been well characterised in a variety of transgenic mouse models, however, non-cognitive behaviours have not been considered as systematically. The non-cognitive behaviour of the hAPP/PS1 transgenic mouse model (TASTPM) was observed at ages spanning the rapid progression of amyloid neuropathology. TASTPM transgenic mice, of both genders, exhibited decreased spontaneous motor activity, disinhibition, increased frequency and duration of feeding bouts, reduced body weight and, by 10 months, increased activity over a 24h period. In addition to the aforementioned behaviours, male transgenic mice also displayed enhanced aggression relative to wildtype controls. These data reveal previously unreported disease relevant behavioural changes that demonstrate the value of measuring behaviour in APP/PS1 transgenic models. These behavioural readouts could be useful in screening putative drug treatments for AD.
阿尔茨海默病（AD）的特征是进行性认知障碍，并伴有神经精神症状，如异常运动行为、抑郁、焦虑、体重减轻、易怒和激动。在多种转基因小鼠模型中，人淀粉样前体蛋白（hAPP）和早老素1（PS1）过表达对认知的影响已得到充分表征，然而，非认知行为尚未得到系统研究。在淀粉样神经病理学快速进展的年龄段观察了hAPP/PS1转基因小鼠模型（TASTPM）的非认知行为。TASTPM转基因小鼠，无论雌雄，均表现出自发运动活动减少、去抑制、进食发作频率和持续时间增加、体重减轻，到10个月时，24小时内的活动增加。除上述行为外，雄性转基因小鼠相对于野生型对照还表现出更强的攻击性。这些数据揭示了以前未报道的与疾病相关的行为变化，证明了在APP/PS1转基因模型中测量行为的价值。这些行为读数可能有助于筛选AD的潜在药物治疗方法。
