Abstract
To investigate whether and how organic anion transporter 1 (OAT1) is involved in the process of Alzheimer’s disease (AD), we crossbred OAT1 knockout mice with tg2576, the widely used AD model mice. Results here showed the heterozygous OAT1-deficient tg2576 mice developed a learning- and memory-related behavior deficiency and higher soluble Abeta amount in early stage (3 months old). Furthermore, the heterozygous mice brain slice also showed impaired long-term potentiation (LTP) and spontaneous excitatory postsynaptic currents (sEPSC). By crossbreeding heterozygous OAT1-deficient tg2576 mice with Thy-1 YFP mice, we got autofluoresced (layer 4/5 cortical neuron) heterozygous mice. By using two-photon microscope in the direct observation of mice brain in vivo or single photon confocal on slices, compared with control tg2576 mice, we found that the OAT1-deficient mice showed a higher spine numbers but with a much lesser maturity extent. Finally, by using glutamate uncaging method, we induced chemical LTP in brain slices and found that OAT1-deficient mice showed abnormal chemical-induced LTP, which meant that the deficient behavior may be caused by abnormal spine morphology and activity. Our results indicated OAT1 may be involved in AD process by regulating spine morphology and activity.
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Acknowledgments
This work was supported by the Natural Science Foundation of Guangdong Province (No. 2011B080701007)
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Xinlin Wu and Jianqing Zhang contributed equally to this work.
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Figure S1
A, Latency to find the platform in water maze escape task. B, Frequency of entries into the non-exiting arms. Data were expressed as Mean ± SEM, n = 6 for each group. Statistical significance was determined using the Student’s t test. C Extracellular LTP recordings in hippocampal slices. (GIF 11 kb)
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Wu, X., Zhang, J., Liu, H. et al. Organic Anion Transporter 1 Deficiency Accelerates Learning and Memory Impairment in tg2576 Mice by Damaging Dendritic Spine Morphology and Activity. J Mol Neurosci 56, 730–738 (2015). https://doi.org/10.1007/s12031-015-0507-8
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DOI: https://doi.org/10.1007/s12031-015-0507-8