Journal
HUMAN MOLECULAR GENETICS
Volume 32, Issue 16, Pages 2558-2575Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddac253
Keywords
-
Ask authors/readers for more resources
NRSF/REST is important for memory performance and synaptic plasticity during aging, but its specific functions in age-dependent and Alzheimer's disease-related memory deficits are still unclear.
NRSF/REST (neuron-restrictive silencer element, also known as repressor element 1-silencing transcription factor), plays a key role in neuronal homeostasis as a transcriptional repressor of neuronal genes. NRSF/REST relates to cognitive preservation and longevity of humans, but its specific functions in age-dependent and Alzheimer's disease (AD)-related memory deficits remain unclear. Here, we show that conditional NRSF/REST knockout either in the dorsal telencephalon or specially in neurons induced an age-dependently diminished retrieval performance in spatial or fear conditioning memory tasks and altered hippocampal synaptic transmission and activity-dependent synaptic plasticity. The NRSF/REST deficient mice were also characterized by an increase of activated glial cells, complement C3 protein and the transcription factor C/EBP & beta; in the cortex and hippocampus. Reduction of NRSF/REST by conditional depletion upregulated the activation of astrocytes in APP/PS1 mice, and increased the C3-positive glial cells, but did not alter the A & beta; loads and memory retrieval performances of 6- and 12-month-old APP/PS1 mice. Simultaneously, overexpression of NRSF/REST improved cognitive abilities of aged wild type, but not in AD mice. These findings demonstrated that NRSF/REST is essential for the preservation of memory performance and activity-dependent synaptic plasticity during aging and takes potential roles in the onset of age-related memory impairments. However, while altering the glial activation, NRSF/REST deficiency does not interfere with the A & beta; deposits and the electrophysiological and cognitive AD-like pathologies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available