Characterization of diabetic neuropathy progression in a mouse model of type 2 diabetes mellitus
Date
2018
Type:
Article
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11 p.
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Abstract
Diabetes mellitus (DM) is one of most common chronic diseases with
an increasing incidence in most countries. Diabetic neuropathy (DN) is
one of the earliest and main complications of diabetic patients, which
is characterized by progressive, distal-to-proximal degeneration of
peripheral nerves. The cellular and molecular mechanisms that trigger
DN are highly complex, heterogeneous and not completely known.
Animal models have constituted a valuable tool for understanding
diabetes pathophysiology; however, the temporal course of DN
progression in animal models of type 2 diabetes (T2DM) is not
completely understood. In this work, we characterized the onset and
progression of DN in BKS diabetic (db/db) mice, including the main
functional and histological features observed in the human disease.
We demonstrated that diabetic animals display progressive sensory
loss and electrophysiological impairments in the early-to-mid phases
of the disease. Furthermore, we detected an early decrease in
intraepidermal nerve fiber (IENF) density in 18-week-old diabetic mice,
which is highly associated with sensory loss and constitutes a reliable
marker of DN. Other common histological parameters of DN – like
Schwann cells apoptosis and infiltration of CD3+ cells in the sciatic
nerve – were altered in mid-to-late phases of the disease. Our results
support the general consensus that DN evolves from initial functional
to late structural changes. This work aimed to characterize the
progression of DN in a reliable animal model sharing the main human
disease features, which is necessary to assess new therapies for this
complex disease. Finally, we also aimed to identify an effective
temporal window where these potential treatments could be
successfully applied.
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Citation
Biology Open, 2018, n° 7, 11 p.
Keywords
Diabetic neuropathy, Type 2 diabetes mellitus, Animal model, Peripheral nerves, Axonal degeneration