Hippocampal GluA2 and GluA4 protein but not corresponding mRNA and promoter methylation levels are modulated at retrieval in spatial learning of the rat

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• 作者：Birgit Rössner ; Maximilian Klingler ; Tanja Bulat ; Ajinkya Sase…
• 关键词：AMPA receptor ; GluA1 ; GluA2 ; GluA3 ; GluA4 ; Morris water maze ; Spatial memory
• 刊名：Amino Acids
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：1
• 页码：117-127
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biochemistry, general; Analytical Chemistry; Biochemical Engineering; Life Sciences, general; Proteomics; Neurobiology;
• 出版者：Springer Vienna
• ISSN：1438-2199
• 卷排序：49

文摘

AMPA receptors mediate most fast excitatory synaptic transmission in the brain. Highly dynamic AMPA receptors are subjected to trafficking, recycling, and/or degradation and replacement. Changes in AMPA receptor abundance is an important mechanism involved in learning and memory formation. Results obtained with the Morris water maze (MWM), a paradigm for testing spatial memory in rodent, correlate with hippocampal synaptic plasticity and NMDA function. Different phases of spatial learning like acquisition and retrieval involve AMPA receptors. Long-term memory formation requires dynamic changes in gene transcription and protein synthesis. It is, however, not known so far if epigenetic marks such as DNA methylation and mRNA levels participate in regulation of AMPA receptors in hippocampus during memory retrieval. In the present study, rats were trained or untrained in the MWM. Steady state levels of hippocampal GluA1–4 mRNA were determined by RT-PCR and promoter methylation levels of GluA1–4 by in-house developed bisulfite pyrosequencing methods. GluA1–4 protein levels were determined in parallel in a membrane fraction by SDS-PAGE followed by Western blotting. Our results indicate that changes of hippocampal membrane AMPA receptors were modulated at the protein level, while no changes were observed at the mRNA and at the promoter methylation level of hippocampal GluA1–4. Training in the MWM at retrieval may, therefore, involve GluA2 and GluA4 subunits that may be regulated by protein stability or trafficking as protein determinations were carried out in a hippocampal membrane fraction.