Effects of accelerated senescence on learning and memory, locomotion and anxiety-like behavior in APP/PS1 mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by a deficit in motor and spatial learning-memory and alteration of non-cognitive behavior. The generation of transgenic mice with presence of AD pathologies that cause learning and memory deficits has led to improved understanding of the behavioral and pathophysiological processes underlying AD. A novel APP/PS1 mouse model in the senescence accelerated mouse prone 8 (SAMP8) background--SAMP8 APP/PS1 was generated. To assess the behavioral and other AD-related changes in this SAMP8 APP/PS1 model, the present report covers a phenotypical analysis of this model for working memory, spatial memory, motor performance and anxiety-like behavior. SAMP8 APP/PS1 mice showed motor and spatial memory impairments, together with an increase of locomotor activity and lower anxiety-like behavior at 9months old. In contrast, C57 APP/PS1 and SAMP8 wild type mice were inconspicuous in all of these tasks and properties except C57 APP/PS1 mice which showed motor memory impairment in the shuttle box task at 9 months old. Standard senescence-associated beta-galactosidase (SA-beta-GAL) staining and amyloid beta (Aβ) immunohistochemistry showed more severe pathological changes in the SAMP8 APP/PS1 mice. SAMP8 APP/PS1 mice exhibited earlier deficits in their non-cognitive and cognitive behaviors which are coincident in the AD patient and the results suggest that this new type of mice might be a better model for studying the age-related dementia of the Alzheimer type and for assessing the potential therapeutic agents for AD.

Lok K ，Zhao H ，Zhang C ，He N ，Shen H ，Wang Z ，Zhao W ，Yin M ... -  《-》

Characterization of the APP/PS1 mouse model of Alzheimer's disease in senescence accelerated background.

The APP/PS1 mouse model of Alzheimer's disease (AD) exhibits remarkable elevation of β-amyloid production associated with certain behavioral abnormalities, while the senescence accelerated mouse prone 8 (SAMP8) is characterized by early and age-related deterioration of learning and memory. In order to obtain an AD model that develops earlier pathological changes and cognitive impairment, we generated SAMP8-APP/PS1, a novel senescence accelerated APP/PS1 transgenic mouse model of AD. Standard histological staining and immunohistochemistry using an amyloid beta (Aβ) antibody showed an age, genotype and strain-dependent progression of amyloid deposition and neuron loss in the cerebral cortex and hippocampus of SAMP8-APP/PS1 mice. Results from the cognitive behavioral tests revealed early deficits in learning and memory in SAMP8-APP/PS1 mice in the two way active avoidance and Morris water maze tests compared with C57-APP/PS1, SAMP8 wild-type and control mice. These results suggest that accelerated senescence exacerbates amyloid deposition and cognitive dysfunction in APP/PS1 mice and the senescence accelerated-APP/PS1 (SAMP8-APP/PS1) mouse model might be a valuable tool to study AD progression and to evaluate the effect of drugs on AD.

Lok K ，Zhao H ，Shen H ，Wang Z ，Gao X ，Zhao W ，Yin M ... -  《-》

Increase in presenilin 1 (PS1) levels in senescence-accelerated mice (SAMP8) may indirectly impair memory by affecting amyloid precursor protein (APP) processing.

Kumar VB ，Franko M ，Banks WA ，Kasinadhuni P ，Farr SA ，Vyas K ，Choudhuri V ，Morley JE ... -  《JOURNAL OF EXPERIMENTAL BIOLOGY》

Sensorimotor gating and memory deficits in an APP/PS1 double transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive deterioration and neuropsychiatric symptoms. Sensorimotor gating deficit has been identified in neuropsychiatric diseases. The aim of the present study was to evaluate the possible sensorimotor gating deficit and its correlation to memory impairment and cerebral β-amyloid (Aβ) plaque deposits in an amyloid precursor protein (APP)/presenilin-1 (PS1) double transgenic mouse model of AD. The sensorimotor gating in 3-, 7- and-22-month-old non-transgenic and transgenic mice was evaluated in a prepulse inhibition (PPI) task. Results revealed that the PPI was lower in the 7- and 22-month-old transgenic mice compared with the age-matched control, while the response to startle pulse-alone in the transgenic and non-transgenic mice was comparable. Congo red staining showed that Aβ neuropathology of transgenic mice aggravated with age, and the 3-month-old transgenic mice started to have minimum brain Aβ plaques, corresponding to the early stage of AD phenotype. Furthermore, memory impairment in the 7-month-old transgenic mice was detected in a water maze test. These results suggest that the sensorimotor gating is impaired with the progressing of AD phenotype, and its deficit may be correlated to cerebral Aβ neuropathology and memory impairment in the APP/PS1 transgenic mouse model of AD.

Wang H ，He J ，Zhang R ，Zhu S ，Wang J ，Kong L ，Tan Q ，Li XM ... -  《-》

Amyloid and tau pathology of familial Alzheimer's disease APP/PS1 mouse model in a senescence phenotype background (SAMP8).

Porquet D ，Andrés-Benito P ，Griñán-Ferré C ，Camins A ，Ferrer I ，Canudas AM ，Del Valle J ，Pallàs M ... -  《-》