4.5 Article

Inhibitory Metaplasticity in Juvenile Stressed Rats Restores Associative Memory in Adulthood by Regulating Epigenetic Complex G9a/GLP

期刊

出版社

OXFORD UNIV PRESS
DOI: 10.1093/ijnp/pyac008

关键词

Juvenile stress; long-term potentiation; synaptic tagging; capture; metaplasticity

资金

  1. National Medical Research Council Collaborative Research Grant [NMRC/OFIRG/0037/2017]
  2. Ministry of Education, Singapore, under its MOE AcRF Tier 3 Award [MOE2017-T3-1-002]
  3. Ministry of Health [MOH-000641-00]
  4. NUSMED-FOS Joint Research Programme [NUHSRO/2018/075/NUSMed-FoS/01]
  5. NUS Research Scholarship, National University of Singapore
  6. Ministry of Science and Technology, Israel [61478]

向作者/读者索取更多资源

Exposure to juvenile stress has long-term effects on the plasticity and quality of associative memory in adulthood. The high expression of the epigenetic marker G9a/GLP complex is found to be one of the mechanisms underlying this effect. Blocking the G9a/GLP complex can alleviate the deficits in long-term plasticity and associative memory caused by juvenile stress.
Background Exposure to juvenile stress was found to have long-term effects on the plasticity and quality of associative memory in adulthood, but the underlying mechanisms are still poorly understood. Methods Three- to four week-old male Wistar rats were subjected to a 3-day juvenile stress paradigm. Their electrophysiological correlates of memory using the adult hippocampal slice were inspected to detect alterations in long-term potentiation and synaptic tagging and capture model of associativity. These cellular alterations were tied in with the behavioral outcome by subjecting the rats to a step-down inhibitory avoidance paradigm to measure strength in their memory. Given the role of epigenetic response in altering plasticity as a repercussion of juvenile stress, we aimed to chart out the possible epigenetic marker and its regulation in the long-term memory mechanisms using quantitative reverse transcription polymerase chain reaction. Results We demonstrate that even long after the elimination of actual stressors, an inhibitory metaplastic state is evident, which promotes synaptic competition over synaptic cooperation and decline in latency of associative memory in the behavioral paradigm despite the exposure to novelty. Mechanistically, juvenile stress led to a heightened expression of the epigenetic marker G9a/GLP complex, which is thus far ascribed to transcriptional silencing and goal-directed behavior. Conclusions The blockade of the G9a/GLP complex was found to alleviate deficits in long-term plasticity and associative memory during the adulthood of animals exposed to juvenile stress. Our data provide insights on the long-term effects of juvenile stress that involve epigenetic mechanisms, which directly impact long-term plasticity, synaptic tagging and capture, and associative memory.

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