Martin Hruska
West Virginia University, WV·Neuroscience
Memory loss in Alzheimer's disease (AD) closely tracks the loss of dendritic spines. These are tiny bumps on neurons where they receive signals from other neurons at junctions called synapses.
- Fields
Neuroscience
Biology
- Topics
Alzheimer's disease
amyloid-beta
dendritic spines
- Grants
- 1 known grant, through Dec 2030
What they work on
- Test how acute amyloid-beta affects PSD-95 stability in spines with different numbers of nanomodules. Use live-cell STED super-resolution imaging, with CRISPR tags on the neurons' own PSD-95 and AMPA receptors.
- Determine whether synapse loss is linked to local compensatory growth of neighboring spines, and whether long-term potentiation-like (LTP-like) structural plasticity, the strengthening that underlies learning, drives it.
- Identify which synapses in the mouse auditory cortex are vulnerable to amyloid-beta and which compensate. Combine slice electrophysiology with multi-color STED imaging of AMPA receptor nanodomains.
- Test whether amyloid-beta destabilizes PSD-95 in small spines through an NMDA receptor, ERK1/2 and ephrin-B3 phosphorylation pathway. Use quantal calcium imaging and STED microscopy.
More about the research
Amyloid-beta (Aβ), the toxic protein that builds up in AD brains, binds to spines and weakens synapses. Yet not all spines respond the same way. Many shrink or vanish, while some grow larger, possibly to make up for failing neighbors. Large surviving spines are seen in patients and in mouse models. Understanding this local compensation could point to ways of restoring synaptic function.
Why it matters
Alzheimer's disease is the leading cause of dementia in the US, affecting an estimated 6.5 million people over 65. By revealing why some synapses survive amyloid-beta and even compensate for lost neighbors, this work could point to molecular targets for preserving or restoring synaptic function. That may inform future therapeutic strategies for AD.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kim Dore
University of California-San Diego, CA·Neuroscience
Measure PSD-95 palmitoylation, the fatty tag that anchors this scaffold protein in synapses, across brain regions differently affected by Alzheimer's in APP/PS1 model mice and postmortem human brain samples.
Johannes W Hell
University of California-Davis, CA·Neuroscience
Test whether norepinephrine taken into neurons by the transporters OCT3 and PMAT activates internal β2ARs to drive GluA1 phosphorylation, AMPAR surface delivery and LTP, using inhibitors, knockout mice, immunoblotting and immunofluorescence.
Karl H Obrietan
Ohio State University, OH·Neuroscience
Test whether circadian clocks in cortico-limbic cells run autonomously and use the core transcription-translation feedback loop (TTFL), using transgenic mice and AAV-based genetic tools.
The school
West Virginia University: 15 labs on PI Pages, $259M a year on research, 201 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.