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/l, 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 mum 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: 1) HR responses to L-Glu injection into the NA at doses of 0.2-0.4 (mM/l, 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.
Yan
Binbin
B
Biomolecular Science Center, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Li
Lihua
L
Harden
Scott W
SW
Epstein
Paul N
PN
Wurster
Robert D
RD
Cheng
Zixi Jack
ZJ
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000294:innervation / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008526:Medulla Oblongata / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008845:Microinjections; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012021:Reflex, Abnormal / Q000502:physiology*; D020421:Vagus Nerve Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
D018698:Glutamic Acid