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Epigenetic Manipulation of Brain-derived Neurotrophic Factor Improves Memory Deficiency Induced by Neonatal
Jiang Wu1, Bihua Bie, Mohamed Naguib
1From the Department of General Anesthesia, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio.
Anesthesiology
|December 10, 2015
Summary
Neonatal anesthesia impairs memory by epigenetically silencing brain-derived neurotrophic factor (BDNF). Environmental enrichment (EE) can reverse these anesthesia-induced memory deficits in rodent models.
Area of Science:
- Neuroscience
- Epigenetics
- Developmental Biology
Background:
- Neonatal anesthesia exposure is linked to memory deficits in rodents and potentially children.
- Mechanisms underlying anesthesia-induced memory impairment are not fully understood.
- Epigenetic modifications affecting brain-derived neurotrophic factor (BDNF) expression are hypothesized to play a role.
Purpose of the Study:
- To investigate the epigenetic mechanisms by which neonatal anesthesia affects memory.
- To determine if environmental enrichment (EE) can counteract anesthesia-induced cognitive deficits.
Main Methods:
- Neonatal rats were exposed to isoflurane anesthesia or sham anesthesia at postnatal day 7.
- Animals were subsequently assigned to either an enriched environment (EE) or standard housing.
- Behavioral, molecular, and electrophysiological assessments were conducted at postnatal day 65.
Main Results:
- Anesthesia reduced hippocampal BDNF expression via epigenetic modifications in the Bdnf promoter region.
- Reduced BDNF led to impaired synaptic protein synthesis, contributing to synaptic and cognitive dysfunction.
- Environmental enrichment (EE) mitigated the anesthesia-induced reduction in BDNF signaling and cognitive deficits.
Conclusions:
- Neonatal anesthesia induces memory deficits through epigenetic silencing of BDNF.
- Environmental enrichment (EE) offers a potential therapeutic strategy to reverse anesthesia-induced cognitive impairment.
