title: Diabetes impairs synaptic plasticity in the superior cervical ganglion: possible role for BDNF and oxidative stress.
abstract: The majority of diabetics develop serious disorders of the autonomic nervous system; however, there is no clear understanding on the causes of these complications. In this study, we examined the effect of streptozocin (STZ)-induced diabetes on activity-dependent synaptic plasticity, associated levels of brain-derived neurotrophic factor (BDNF) and antioxidant biomarkers in the rat sympathetic superior cervical ganglion. Diabetes (STZ-induced) was achieved by a single intraperitoneal injection of streptozocin (55 mg/kg).Compound action potentials were recorded from isolated ganglia before (basal) and after repetitive stimulation, or trains of paired pulses to express ganglionic long-term potentiation (gLTP) or long-term depression (gLTD). The input/output curves of ganglia from STZ-treated animals showed a marked rightward shift along most stimulus intensities, compared to those of ganglia from control animals, indicating impaired basal synaptic transmission in ganglia from STZ-induced diabetic animals. Repetitive stimulation induced robust gLTP and gLTD in ganglia isolated from control animals; the same protocols failed to induce gLTP or gLTD in ganglia from STZ-induced diabetic animals, indicating impairment of activity-dependent synaptic plasticity in these animals. Molecular analysis revealed significant reduction in the levels of BDNF and the ratio of glutathione/oxidized glutathione. Additionally, the activity of glutathione peroxidase, glutathione reductase, catalase, and the levels of thiobarbituric acid-reactive substances were increased in ganglia from STZ-treated animals. In conclusion, impaired basal synaptic transmission and synaptic plasticity are associated with reduced BDNF and altered oxidative stress biomarkers in the sympathetic ganglia from STZ-induced diabetic animals, suggesting a possible correlation of these factors with the manifestations of STZ-induced diabetes in the peripheral nervous system.
authors.affiliation: Faculty of Pharmacy, Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: K H
authors.initials: KH
authors.lastname: Alzoubi
authors.forename: O F
authors.initials: OF
authors.lastname: Khabour
authors.forename: I A
authors.initials: IA
authors.lastname: Alhaidar
authors.forename: A M
authors.initials: AM
authors.lastname: Aleisa
authors.forename: K A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000200:Action Potentials; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D017774:Long-Term Potentiation; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017783:Superior Cervical Ganglion / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005978:Glutathione