Experimental diabetes in neonatal mice induces early peripheral sensorimotor neuropathy.
Animal models of diabetes do not reach the severity of human diabetic neuropathy but relatively mild neurophysiological deficits and minor morphometric changes. The lack of degenerative neuropathy in diabetic rodent models seems to be a consequence of the shorter length of the axons or the shorter animal life span. Diabetes-induced demyelination needs many weeks or even months before it can be evident by morphometrical analysis. In mice myelination of the peripheral nervous system starts at the prenatal period and it is complete several days after birth. Here we induced experimental diabetes to neonatal mice and we evaluated its effect on the peripheral nerve 4 and 8 weeks after diabetes induction. Neurophysiological values showed a decline in sensory nerve conduction velocity at both time-points. Morphometrical analysis of the tibial nerve demonstrated a decrease in the number of myelinated fibers, fiber size and myelin thickness at both time-points studied. Moreover, aldose reductase and poly(ADP-ribose) polymerase activities were increased even if the amount of the enzyme was not affected. Thus, type 1 diabetes in newborn mice induces early peripheral neuropathy and may be a good model to assay pharmacological or gene therapy strategies to treat diabetic neuropathy.
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
L
L
Ariza
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
G
G
Pagès
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
B
B
García-Lareu
Department of Cell Biology, Physiology and Immunology and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Spain.
S
S
Cobianchi
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
P J
PJ
Otaegui
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Department of Animal Health and Anatomy, Veterinary School, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
J
J
Ruberte
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain; Institut Català de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
M
M
Chillón
Department of Cell Biology, Physiology and Immunology and Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Spain.
X
X
Navarro
Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: assumpcio.bosch@uab.es.
A
A
Bosch
D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D021461:Animals, Outbred Strains; D001786:Blood Glucose; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology*; D005528:Foot / Q000294:innervation / Q000473:pathology; D008297:Male; D051379:Mice; D009186:Myelin Sheath / Q000473:pathology / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000294:innervation / Q000473:pathology
D001786:Blood Glucose; D000449:Aldehyde Reductase; D011065:Poly(ADP-ribose) Polymerases
PARP activity; aldose reductase activity; diabetic neuropathy; myelination; neonatal mice