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Updated: Jul 11, 2025
Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke
Published on: March 22, 2016
A rat model established by simulating genetic-environmental interactions recapitulates human Alzheimer's disease
Xiaomei Lin1, Tianyuyi Feng1, Erheng Cui1
1Department of Imaging, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200000, China.
Background:
In humans, Alzheimer's disease (AD) is typically sporadic in nature, and its pathology is usually influenced by extensive factors. The study established a rat model based on the genetic-environmental interaction.
Methods:
A rat model was established by transduction of an adeno-associated virus combined with acrolein treatment. Rats were assigned to the normal control (NC), acrolein group, AAV (-) group, AAV-APP group, and AAV-APP/acrolein group. The success of model construction was verified in multiple ways, including by assessing cognitive function, examining microstructural changes in the brain in vivo, and performing immunohistochemistry. The contribution of genetic (APP mutation) and environmental (acrolein) factors to AD-like phenotypes in the model was explored by factorial analysis.
Results:
1) The AAV-APP/acrolein group showed a decline in cognitive function, as indicated by a reduced gray matter volume in key cognition-related brain areas, lower FA values in the hippocampus and internal olfactory cortex, and Aβ deposition in the cortex and hippocampus. 2) The AAV-APP group also showed a decline in cognitive function, although the group exhibited atypical brain atrophy in the gray matter and insignificant Aβ deposition. 3) The acrolein group did not show any significant changes in Aβ levels, gray matter volume, or cognitive function. 4) The genetic factor (APP mutation) explained 39.74% of the AD-like phenotypes in the model factors, and the environmental factor (acrolein exposure) explained 33.3%.
Conclusions:
The genetic-environmental interaction rat model exhibited a phenotype that resembled the features of human AD and will be useful for research on AD.
