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P2‐035: Melatonin rescues synaptic/memory impairment by regulating the levels of c‐fos in tg2576 mice
Author(s) -
Peng Caixia
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.571
Subject(s) - synaptic plasticity , morris water navigation task , melatonin , synapse , creb , neuroscience , arc (geometry) , fear conditioning , psychology , cued speech , hippocampus , biology , medicine , endocrinology , receptor , transcription factor , biochemistry , geometry , mathematics , amygdala , cognitive psychology , gene
Background: Synaptic communication forms the basis of learning and memory. Disruptions of synaptic function and memory have been widely reported in many neurological diseases, such as dementia. Melatonin rescues synaptic/memory impairment in Alzheimer’s animal model, but the mechanisms are unknown. We recorded the ethology, and detected the protein expression of synapse associated proteins and CREB, and then tested the mRNA and protein levels of Arc and c-fos, important immediate early gene that is crucial for maintaining normal synaptic plasticity to elucidate the mechanisms underlying such alterations. Methods: 20 Tg2576 mice were randomly divided into 2 groups-melatonin group and control group. We injected intraperitoneally with 10 mg/kg of melatonin or 0.9% normal saline as vehicle control once a day for 8 to 12 months. Then, in order to detect learning and memory ability of the mice, wemeasuredmorris water maze, contextual and cued fear conditioning and step-down type passive avoidance. Synapse associated proteins (PSD95, synaptophisin) and CREB were detected by Western blotting, the expression of Arc and c-fos were detected by RT-PCR and Western blotting. Results: Melatonin group can significant shorten the escape latency and increased the target platform crossings in morris water maze test, prolonged the step-down latency and reduce count of error in step-down type passive avoidance test, extended the time of contextual freezing and cued freezing, but no significant differences compared with control group in the time of immediate freezing for fear conditioning task. Melatonin group increased the protein expression of the synapse-associated proteins (PSD95, synaptophisin), the memory-associated early response genes (arc and c-fos) and CREB in hippocampus extracts, rescued the mRNA levels of arc and c-fos. Conclusions: Melatonin administration increases the protein expression of PSD95, synaptophisin, arc, c-fos and CREB with improvement of learning and memory. So we presumed that melatonin improves memory deficits and promotes neurogenesis in transgenicmice ofAlzheimer’s Disease via up regulation the mRNA levels of arc and c-fos.