Synaptic input changes to spinal cord motoneurons correlate with motor control impairments in a type 1 diabetes mellitus model

Brain and Behavior

Suzana Ulian Benitez¹  Everardo Magalhães Carneiro¹ 

[1] Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Sao Paulo, Brazil

关键词: Diabetes mellitus;    motoneuron;    nonobese diabetic mice model;    spinal cord;    synaptic terminals;    ventral horn;   

DOI  :  10.1002/brb3.372

来源: Wiley

【 摘 要 】

Abstract

Introduction

Hyperglycemia is the main cause of diabetic complications, contributing to a widespread degeneration of the nervous system. Nevertheless, the main focus has been the sensory neurons because of neuropathic pain, while the impairments associated with the spinal cord and motor deficits, mostly of those initiated at early stages of the disease, have been poorly investigated. In this way, the present study used the nonobese diabetic mouse model to evaluate the microenvironment around motoneurons at ventral horn of the spinal cord, following prolonged hyperglycemia.

Methods

Adult female mice were divided into two groups: spontaneously diabetic (n = 33) and nondiabetic (n = 26). Mice were considered hyperglycemic when blood glucose surpassed 400 mg/dL. Following 2 weeks from that stage, part of the animals was euthanized and the lumbar intumescences were obtained and processed for immunohistochemistry and transmission electron microscopy. For immunohistochemistry, the antibodies used for integrated density of pixels quantification were anti-synaptophysin, anti-GFAP, and anti-Iba1. The functional analysis was monitored with the walking track test (CatWalk system) during 4 weeks.

Results

The results revealed significant motor impairment in diabetic animals in comparison to the control group. Such loss of motor control correlated with a significant reduction in presynaptic terminals apposed to the motoneurons. Nevertheless, there were no significant changes in glial reaction in the spinal cord.

Conclusion

Overall, the results herein revealed central nervous system changes at early stages of the disease that may in turn contribute to the motor deficit. Such changes open a new window of investigation in early stages of diabetes to better comprehend motor impairment as a long-term complication of the disease.

【 授权许可】

CC BY   
© 2015 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

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