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RESEARCH
FOCUS
Neurodegeneration and Neuroprotection
Our research focuses on the basic cellular events in normal nerve and
nerve diseases during axonal degeneration, in order to better understanding
mechanisms of neuroprotection and neuroregeneration. Indeed it has been now
demonstrated that the dismantling of injured axons is an active process,
analogous to apoptotic cell death. Axonal degeneration occurs in a wide variety
of neurological diseases including peripheral neuropathies and central nervous
system neurodegenerative disorders like Alzheimer disease and Parkinson
disease. Moreover axonal degeneration is now known to be implicated in the late
phase of multiple sclerosis. As the phenomenon of axonal degeneration is better
understood, axonal protection and neuronal regeneration become more approachable
topics of investigation and intervention.
In particular we explore axonal damage and mechanisms of
neuroprotection in in vitro models of toxic and diabetic neuropathies, that
closely mimic the in vivo situation. We use dissociated cultures of sensory
neurons, harvested from embryonic rat dorsal root ganglia and expose them to
different toxic agents. The system allows us to investigate cell pathways of
axonal degeneration and potential neuroprotective agents.
Compartmentalized cell culture system (Campenot
Chambers)
In our lab we have
set up a compartmentalized cell culture system, known as Campenot chambers
(Campenot, 1977). In compartmentalized chambers, axons grow across a silicone
grease barrier and enter a separate fluid environment within a distal
compartment, which allows pharmacological manipulation of distal axons
independently from cell bodies. This powerful system has been successfully used
to study the formation and maintenance of neuronal projections. We exploit this
system to study the differential and potentially multiple insults of toxic
agents on cell bodies and axons and in parallel to investigate which are the
different pathways activated by cells and distal axons in response to neuroprotective
agents.
Representative
Publications
Melli G, Hoke A. Canadian Association Review: Regulation of myelination
by trophic factors and neuron-glia signaling. Canadian Journal of Neurological
Sciences, 2007; 34: 288-95
Melli G, Jack C, Lambrinos GL, Ringkamp M, Ahmet Höke. Erythropoietin protects
sensory axons against paclitaxel-induced distal degeneration. Neurobiology of
disease, 2006; 24(3):525-30
Melli G, Keswani SC, Fisher A, Chen W, Hoke A. Spatially
distinct and functionally independent mechanisms of axonal degeneration in a
model of HIV associated sensory neuropathy. Brain 2006; 129:1330-38.
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