| First Author | Roy A | Year | 2013 |
| Journal | Cell Rep | Volume | 4 |
| Issue | 4 | Pages | 724-37 |
| PubMed ID | 23972989 | Mgi Jnum | J:202856 |
| Mgi Id | MGI:5522618 | Doi | 10.1016/j.celrep.2013.07.028 |
| Citation | Roy A, et al. (2013) Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator-activated receptor alpha. Cell Rep 4(4):724-37 |
| abstractText | Peroxisome proliferator-activated receptor alpha (PPARalpha) is a transcription factor that regulates genes involved in fatty acid catabolism. Here, we provide evidence that PPARalpha is constitutively expressed in nuclei of hippocampal neurons and, surprisingly, controls calcium influx and the expression of various plasticity-related genes via direct transcriptional regulation of cyclic AMP response element binding (CREB). Accordingly, Pparalpha-null, but not Pparbeta-null, mice are deficient in CREB and memory-associated proteins and have decreased spatial learning and memory. Small hairpin RNA knockdown of PPARalpha in the hippocampus suppressed CREB and NR2A, rendering wild-type animals markedly poor in consolidating spatial memory, whereas introduction of PPARalpha to the hippocampus of Pparalpha-null mice increased hippocampal CREB and NR2A and improved spatial learning and memory. Through detailed analyses of CREB and NR2A activity, as well as spatial learning and memory in bone marrow chimeric animals lacking PPARalpha in the CNS, we uncover a mechanism for transcriptional control of Creb and associated plasticity genes by PPARalpha. |
