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Published on: March 23, 2011
Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington's disease
Hongyu Zhang1,2,3, Chunlei Zhang4,5, Jean Vincent4,5
1Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, 33076, France. hongyu.zhang@uib.no.
Nature Communications
|October 17, 2018
Summary
Huntington's disease impairs hippocampal synaptic plasticity by disrupting AMPAR surface diffusion. The antidepressant tianeptine rescues this defect and restores memory in HD models.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Huntington's disease (HD) is a neurodegenerative disorder characterized by cognitive impairment.
- Impaired hippocampal synaptic plasticity is a key contributor to cognitive deficits in HD.
- The precise molecular mechanisms underlying these synaptic plasticity defects remain incompletely understood.
Purpose of the Study:
- To investigate the molecular basis of impaired hippocampal synaptic plasticity in Huntington's disease.
- To explore the role of AMPAR surface diffusion and its regulation in HD.
- To identify potential therapeutic targets for cognitive dysfunction in HD.
Main Methods:
- Live-cell nanoparticle tracking and super-resolution imaging were employed in rodent models of HD.
- Investigated the brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling pathway.
- Assessed the effects of the antidepressant tianeptine on AMPAR trafficking, synaptic plasticity, and memory.
Main Results:
- AMPAR surface diffusion, crucial for synaptic plasticity, was found to be disturbed in HD models.
- Defects in the BDNF-TrkB signaling pathway were linked to deregulated AMPAR trafficking.
- Tianeptine treatment rescued disturbed AMPAR surface diffusion and restored long-term potentiation (LTP) and hippocampus-dependent memory in HD mice.
Conclusions:
- Disrupted AMPAR surface diffusion is a key mechanism underlying hippocampal synaptic and memory dysfunction in HD.
- The BDNF-TrkB pathway plays a critical role in regulating AMPAR trafficking in the context of HD.
- Tianeptine shows therapeutic potential by targeting AMPAR surface diffusion via the BDNF pathway for HD-related cognitive impairment.
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