Definition of a Bidirectional Activity-Dependent Pathway Involving BDNF and Narp

Autor: Abigail Mariga, Juliane Glaser, Leo Mathias, Desheng Xu, Meifang Xiao, Paul Worley, Ipe Ninan, Moses V. Chao
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Cell Reports, Vol 13, Iss 9, Pp 1747-1756 (2015)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2015.10.064
Popis: One of the cardinal features of neural development and adult plasticity is the contribution of activity-dependent signaling pathways. However, the interrelationships between different activity-dependent genes are not well understood. The immediate early gene neuronal-activity-regulated pentraxin (NPTX2 or Narp) encodes a protein that has been associated with excitatory synaptogenesis, AMPA receptor aggregation, and the onset of critical periods. Here, we show that Narp is a direct transcriptional target of brain-derived neurotrophic factor (BDNF), another highly regulated activity-dependent gene involved in synaptic plasticity. Unexpectedly, Narp is bidirectionally regulated by BDNF. Acute BDNF withdrawal results in downregulation of Narp, whereas transcription of Narp is greatly enhanced by BDNF. Furthermore, our results show that BDNF directly regulates Narp to mediate glutamatergic transmission and mossy fiber plasticity. Hence, Narp serves as a significant epistatic target of BDNF to regulate synaptic plasticity during periods of dynamic activity.
Databáze: Directory of Open Access Journals