Diabetes induces neural degeneration in nucleus ambiguus (NA) and attenuates heart rate control in OVE26 mice

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.