Diabetes induces neural degeneration in nucleus ambiguus (NA) and attenuates heart rate control in OVE26 mice
Abbreviated Journal Title
Baroreflex; Nucleus ambiguus; Vagal efferent; Cardiac ganglia; Type 1; diabetes; OVE26 mice; CHRONIC INTERMITTENT HYPOXIA; LATERAL TEGMENTAL FIELD; VAGAL; PREGANGLIONIC NEURONS; VENTRAL RESPIRATORY GROUP; CARDIAC GANGLIA; SUBNUCLEAR ORGANIZATION; FUNCTIONAL-SIGNIFICANCE; SPECTRAL-ANALYSIS; TRANSGENIC MICE; MOTOR-NEURONS; Neurosciences
Baroreflex sensitivity is impaired by diabetes mellitus. Previously, we found that diabetes induces a deficit of central mediation of baroreflex-mediated bradycardia. In this study, we assessed whether diabetes induces degeneration of the nucleus ambiguus (NA) and reduces heart rate (HR) responses to L-Glutamate (L-Glu) microinjection into the NA. FVB control and OVE26 diabetic mice (5-6 months) were anesthetized. Different doses of L-Glu (0.1-5 mM/1, 20 nl) were delivered into the left NA using a multi-channel injector. In other animals, the left vagus was electrically stimulated at 1-40 Hz (1 ms, 0.5 mA, 20 s). HR and mean arterial blood pressure (MAP) responses to L-Glu microinjections into the NA and to the electrical stimulation of the vagus were measured. The NA region was defined by tracer TMR-D injection into the ipsilateral nodose ganglion to retrogradely label vagal motoneurons in the NA. Brainstem slices at -600, -300, 0, +300, and +600 mu m relative to the obex were processed using Nissl staining and the number of NA motoneurons was counted. Compared with FVB control, we found in OVE26 mice that: I) HR responses to L-Glu injection into the NA at doses of 0.2-0.4 (mM/1, 20 nl) were attenuated (p<0.05), but MAP responses were unchanged (p>0.05). 2) HR responses to vagal stimulation were increased (p<0.05). 3) The total number of NA (left and right) motoneurons was reduced (p<0.05). Taken together, we concluded that diabetes reduces NA control of HR and induces degeneration of NA motoneurons. Degeneration of NA cardiac motoneurons may contribute to impairment of reflex-bradycardia in OVE26 diabetic mice. (C) 2009 Elsevier Inc. All rights reserved.
"Diabetes induces neural degeneration in nucleus ambiguus (NA) and attenuates heart rate control in OVE26 mice" (2009). Faculty Bibliography 2000s. 2348.