The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression - PubMed (original) (raw)

Comparative Study

. 2006 Feb 2;49(3):341-8.

doi: 10.1016/j.neuron.2005.12.027.

Affiliations

Free article

Comparative Study

The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression

Qiang Chang et al. Neuron. 2006.

Free article

Abstract

Mutations in the MECP2 gene cause Rett syndrome (RTT). Bdnf is a MeCP2 target gene; however, its role in RTT pathogenesis is unknown. We examined Bdnf conditional mutant mice for RTT-relevant pathologies and observed that loss of BDNF caused smaller brain size, smaller CA2 neurons, smaller glomerulus size, and a characteristic hindlimb-clasping phenotype. BDNF protein level was reduced in Mecp2 mutant mice, and deletion of Bdnf in Mecp2 mutants caused an earlier onset of RTT-like symptoms. To assess whether this interaction was functional and potentially therapeutically relevant, we increased BDNF expression in the Mecp2 mutant brain with a conditional Bdnf transgene. BDNF overexpression extended the lifespan, rescued a locomotor defect, and reversed an electrophysiological deficit observed in Mecp2 mutants. Our results provide in vivo evidence for a functional interaction between Mecp2 and Bdnf and demonstrate the physiological significance of altered BDNF expression/signaling in RTT disease progression.

PubMed Disclaimer

Comment in

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources