Title

Structural Remodeling Of Vagal Afferent Innervation Of Aortic Arch And Nucleus Ambiguus (Na) Projections To Cardiac Ganglia In A Transgenic Mouse Model Of Type 1 Diabetes (Ove26)

Keywords

aortic arch; baroreceptor afferent; baroreflex; cardiac ganglia; diabetes; nodose ganglion; nucleus ambiguus; OVE26 mce; vagal efferent

Abstract

Diabetes-induced structural changes of vagal aortic afferent and cardiac efferent axons are not well understood. FVB control and OVE26 diabetic mice at different ages received injections of the tracer tetramethylrhodamine dextran (TMR-D) into the nodose ganglion to label vagal aortic afferents (at 3 and 6 months), or DiI injections into the nucleus ambiguus to label vagal cardiac efferents (at 3, 6, and 9 months). The aortic arch and atria were examined by using confocal microscopy. In the aortic arch, TMR-D labeled large and small vagal afferent axons (axonsL and axonsS) that formed different types of terminals: axonsL produced large flower-sprays (flower-spraysL) and end-nets (end-netsL), whereas axonsS produced small flower-sprays (flower-spraysS) and end-nets (end-netsS). In the atria, DiI-labeled vagal efferent axons formed basket endings around ganglion principle neurons (PNs). The vagal afferents, PNs and vagal cardiac efferents in diabetic mice were compared with age-matched control mice. We found (P < 0.05) that: 1) the size of axonsL, flower-spraysL, flower-spraysS and end-netsS were reduced at 6 and 9 months; 2) the size of cardiac ganglia and the somatic area of the PNs were decreased, and the PN density in cardiac ganglia was increased at all ages and the PN nuclei/soma area ratio was increased at 9 months; and 3) the percentage of DiI-labeled axons-innervated PNs was decreased at all ages. Furthermore, the number of synaptic-like terminal varicosities around PNs was decreased. Compared with 3 months, more advanced diabetes at 9 months further reduced the number of varicosities/PN. In addition to these changes, swollen axons and terminals, as well as leaky-like DiI-labeled terminals, were observed in long-term diabetic mice (6 and 9 months of age). Taken together, our data show that chronic diabetes induces a significant structural atrophy of vagal aortic afferent and cardiac efferent axons and terminals. Although different morphologies of vagal afferent terminals in the aortic arch may serve as substrates for the future investigation of aortic depressor afferent physiology, structural remodeling of vagal afferents and efferents provides a foundation for further analysis of diabetesinduced impairment of cardiac autonomic regulation. J. Comp. © 2010 Wiley-Liss, Inc.

Publication Date

7-15-2010

Publication Title

Journal of Comparative Neurology

Volume

518

Issue

14

Number of Pages

2771-2793

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1002/cne.22363

Socpus ID

77954582019 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/77954582019

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