Cardiotrophin-1 (CTF1) ameliorates glucose-uptake defects and improves memory and learning deficits in a transgenic mouse model of Alzheimer's disease.

Research paper by Dongmei D Wang, Xiaoying X Li, Kai K Gao, Dan D Lu, Xu X Zhang, Chunmei C Ma, Fei F Ye, Lianfeng L Zhang

Indexed on: 02 Apr '13Published on: 02 Apr '13Published in: Pharmacology Biochemistry and Behavior


Cardiotrophin-1 (CTF1) has been reported to act as a trophic factor for a few neurons, such as sensory, cholinergic, dopaminergic, motor and cortical neurons. Studies have indicated that CTF1 delays degenerative disease progression in motor neuron disease. However, little is known about the effects of CTF1 on degenerative disease in the brain. We have shown that expression of CTF1 is strongly down-regulated in the brain of the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease (AD). Transgenic mice with brain tissue-specific CTF1 expression alone or in combination with APPswe/PS1dE9 transgenic mice were produced to study the effects of CTF1 on AD. CTF1 expressing APPswe/PS1dE9 transgenic mice exhibited improvements in learning and memory, less severe abnormalities in locomotor activity, reduced scattered senile plaques and ameliorated disturbances of brain energy metabolism compared to APPswe/PS1dE9 transgenic mice. Furthermore, CTF1 inhibited the activity of glycogen synthase kinase-3β (GSK-3β) in SH-SY5Y cell line and in the brain tissues of APPswe/PS1dE9 transgenic mice. The transgenic expression of CTF1 compensated for the loss of CTF1 expression and brought about a marked improvement on cognitive functioning in the APPswe/PS1dE9 transgenic mouse model of Alzheimer's disease, suggesting that the inhibition of GSK-3β activity might play an important role.