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

Experimental Neurobiology
Hyungju Park

Abstract

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 corticostriata...Continue Reading

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Citations

Jul 23, 2019·Cerebral Cortex·Giuseppe GangarossaLaurent Venance
Sep 19, 2020·Cell and Tissue Research·Tanja Brigadski, Volkmar Leßmann
Aug 9, 2019·Journal of Neuroscience Research·Francisco M Torres-CruzElizabeth Hernández-Echeagaray
Mar 19, 2021·JAAPA : Official Journal of the American Academy of Physician Assistants·Jennifer de la Cruz, Joseph Hwang
Feb 6, 2021·Journal of Neurochemistry·Callista B Harper, Karen J Smillie

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Methods Mentioned

BETA
antisense nucleotide
GTPase

Software Mentioned

Prism
ImageJ
GraphPad

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