| First Author | Yang Y | Year | 2023 |
| Journal | Hum Mol Genet | Volume | 32 |
| Issue | 16 | Pages | 2558-2575 |
| PubMed ID | 36229920 | Mgi Jnum | J:339345 |
| Mgi Id | MGI:7520645 | Doi | 10.1093/hmg/ddac253 |
| Citation | Yang Y, et al. (2023) NRSF regulates age-dependently cognitive ability and its conditional knockout in APP/PS1 mice moderately alters AD-like pathology. Hum Mol Genet 32(16):2558-2575 |
| abstractText | 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/EBPbeta 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 Abeta 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 Abeta deposits and the electrophysiological and cognitive AD-like pathologies. |
