Similar pattern of peripheral neuropathy in mouse models of type 1 diabetes and Alzheimer's disease

Abstract There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer's disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predomi...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience 2012-01, Vol.202, p.405-412
Main Authors: Jolivalt, C.G, Calcutt, N.A, Masliah, E
Format: Article
Language:English
Subjects:
Alzheimer Disease - pathology
Alzheimer's disease
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - metabolism
amyloid precursor protein
Animals
Biological and medical sciences
Blotting, Western
Brain Chemistry - physiology
Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction
diabetes
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - pathology
Diabetes Mellitus, Type 1 - pathology
Diabetic Neuropathies - pathology
diabetic neuropathy
Fundamental and applied biological sciences. Psychology
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
Humans
Immunohistochemistry
insulin signaling
Male
Medical sciences
Mice
Mice, Transgenic
Nervous system (semeiology, syndromes)
Neural Conduction - physiology
Neurology
Peripheral Nervous System Diseases - pathology
Phosphorylation
sciatic nerve
Sciatic Neuropathy - pathology
Sensory Thresholds - physiology
Thermosensing - physiology
Touch - physiology
Ubiquitin Thiolesterase - metabolism
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract There is an increasing awareness that diabetes has an impact on the CNS and that diabetes is a risk factor for Alzheimer's disease (AD). Links between AD and diabetes point to impaired insulin signaling as a common mechanism leading to defects in the brain. However, diabetes is predominantly characterized by peripheral, rather than central, neuropathy, and despite the common central mechanisms linking AD and diabetes, little is known about the effect of AD on the peripheral nervous system (PNS). In this study, we compared indexes of peripheral neuropathy and investigated insulin signaling in the sciatic nerve of insulin-deficient mice and amyloid precursor protein (APP) overexpressing transgenic mice. Insulin-deficient and APP transgenic mice displayed similar patterns of peripheral neuropathy with decreased motor nerve conduction velocity, thermal hypoalgesia, and loss of tactile sensitivity. Phosphorylation of the insulin receptor and glycogen synthase kinase 3β (GSK3β) was similarly affected in insulin-deficient and APP transgenic mice despite significantly different blood glucose and plasma insulin levels, and nerve of both models showed accumulation of Aβ-immunoreactive protein. Although diabetes and AD have different primary etiologies, both diseases share many abnormalities in both the brain and the PNS. Our data point to common deficits in the insulin-signaling pathway in both neurodegenerative diseases and support the idea that AD may cause disorders outside the higher CNS.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2011.11.032