title: Changes in cardiac innervation during maturation in long-term diabetes.
abstract: Diabetic autonomic neuropathy being a common complication of diabetes mellitus (DM) is related to an increased risk of cardiovascular mortality. However, mechanisms underlying changes of innervation density in affected hearts remain insufficiently understood. Hence, the aim of this study was to describe quantitative changes of intra-myocardial nerve terminals in hearts of diabetic rats of various ages. Male Sprague-Dawley rats were injected with 55mg/kg streptozotocin (STZ) (DM group) or with citrate buffer (control). After 2weeks, 2months, 6months and 12months, sections of their hearts were analyzed in five areas-left ventricle, interventricular septum, right ventricle, anterior and posterior wall. Nerve fibers were visualized immunohistochemically, using antibody against a general neuronal marker, protein gene product 9.5 (PGP 9.5). Significant increase in total nerve fibers from all heart areas was observed 2weeks and 2months after diabetes induction, followed by a decrease at 6months and again increase at 12months was observed in both control and diabetic rats. Significant difference between control and diabetic rats was visible after 2weeks and 2months, with diabetic rats exhibiting significantly more nerve fibers. There were no consistent differences in quantity of nerve fibers in different areas of the heart within a particular age-related group of animals. In conclusion, cardiac innervation undergoes dynamic changes both in control and in diabetic rats, with a time-dependent significant increase in neuronal fiber density in diabetic animals. This novel information may contribute to our understanding of pathophysiological changes associated with diabetic cardiac neuropathy.
authors.affiliation: Laboratory for Neurocardiology, University of Split School of Medicine, Soltanska 2, 21000 Split, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Bakovic
authors.forename: Marina
authors.initials: M
authors.lastname: Juric Paic
authors.forename: Elena
authors.initials: E
authors.lastname: Zdrilic
authors.forename: Katarina
authors.initials: K
authors.lastname: Vukojevic
authors.forename: Lejla
authors.initials: L
authors.lastname: Ferhatovic
authors.forename: Ana
authors.initials: A
authors.lastname: Marin
authors.forename: Natalija
authors.initials: N
authors.lastname: Filipovic
authors.forename: Ivica
authors.initials: I
authors.lastname: Grkovic
authors.forename: Livia
authors.initials: L
authors.lastname: Puljak
mesh_terms: D000367:Age Factors; D000818:Animals; D001341:Autonomic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000503:physiopathology; D006321:Heart / Q000294:innervation*; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase
keywords: Diabetes mellitus; Heart; Innervation; Neuropathy; PGP 9.5