• the Korean Society for Brain and Neural Sciences


Original Article

Exp Neurobiol 2018; 27(3): 217-225

Published online June 30, 2018

© The Korean Society for Brain and Neural Sciences

Cortical Axonal Secretion of BDNF in the Striatum Is Disrupted in the Mutant-huntingtin Knock-in Mouse Model of Huntington’s Disease

Hyungju Park1,2*

1Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA, 2Molecular Neurobiology Lab, Department of Structure and Function of Neural Network, Korea Brain Research Institute, Daegu 41062, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: 82-53-980-8450, FAX: 82-53-980-8339

Received: April 19, 2018; Revised: May 23, 2018; Accepted: May 25, 2018

Deficient BDNF signaling is known to be involved in neurodegenerative diseases such as Huntington's disease (HD). Mutant huntingtin (mhtt)-mediated disruption of either BDNF transcription or transport is thought to be a factor contributing to striatal atrophy in the HD brain. Whether and how activity-dependent BDNF secretion is affected by the mhtt remains unclear. In the present study, I provide evidence for differential effects of the mhtt on cortical BDNF secretion in the striatum during HD progression. By two-photon imaging of fluorescent BDNF sensor (BDNF-pHluorin and -EGFP) in acute striatal slices of HD knock-in model mice, I found deficient cortical BDNF secretion regardless of the HD onset, but antisense oligonucleotide (ASO)-mediated reduction of htts only rescues BDNF secretion in the early HD brain before the disease onset. Although secretion modes of individual BDNF-containing vesicle were not altered in the pre-symptomatic brain, the full-fusion and partial-fusion modes of BDNF-containing vesicles were significantly altered after the onset of HD symptoms. Thus, besides abnormal BDNF transcription and transport, our results suggest that mhtt-mediated alteration in activity-dependent BDNF secretion at corticostriatal synapses also contributes to the development of HD.

Graphical Abstract

Keywords: BDNF, Huntington’s disease, antisense oligonucleotide, corticostriatal synapse