Premium
Developing manganese‐enhanced MRI as a non‐invasive measure of in vivo neuronal activity in the rostral ventrolateral medulla (RVLM) of sedentary and physically active rats
Author(s) -
Huereca Daniel J,
Holt Avril G,
Berkowitz Bruce A,
Mueller Patrick J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.756.3
Subject(s) - rostral ventrolateral medulla , chemistry , in vivo , medicine , premovement neuronal activity , endocrinology , magnetic resonance imaging , neuroscience , medulla oblongata , central nervous system , psychology , biology , microbiology and biotechnology , radiology
Elevated sympathetic nerve activity (SNA) is implicated as a major risk factor for cardiovascular disease (CVD). We have previously demonstrated greater SNA in sedentary versus physically active rats following direct and indirect activation of the RVLM, the primary regulator of SNA. We have also reported changes in structure among spinally projecting neurons in the RVLM, including greater dendritic branching in sedentary versus physically active rats. These studies indicate that sedentary conditions promote structural and functional changes within the RVLM linked with increased SNA. The aim of the present study was to develop a new method, manganese‐enhanced magnetic resonance imaging (MEMRI), to compare changes in RVLM activity over time in sedentary versus physically active rats. MEMRI utilizes both the paramagnetic properties of manganese (Mn 2+ ) as well as its uptake by active neurons. Mn 2+ is a T1 MRI contrast agent that enters active neurons via calcium channels, thus, greater manganese uptake indicates greater neuronal activity. We hypothesized that the enhanced SNA in sedentary versus physically active rats is due to greater activity of bulbospinal RVLM neurons. To evaluate the influence of sedentary and physically active conditions on in vivo neuronal activity of the RVLM longitudinally, five week old male Sprague Dawley rats (n=4) were anesthetized (2% isoflurane) and RVLMs were imaged on a 7T small animal MRI (Bruker ClinScan). One week later, changes in T1 were evaluated 24 hours after an i.p. injection of manganese (66mg/kg MnCl 2 ). Two rats were then each assigned randomly to a sedentary or physically active group (spontaneous wheel running). After five weeks (24 hours after a 2 nd injection of MnCl 2 ), Mn 2+ uptake was greater in the RVLM of sedentary versus physically active rats, regardless of the method used for collection and analysis of the MRI data; T1 weighted (+16.3% vs +6.8% signal increase) or T1 mapping (1/T1=0.81 vs 0.69). Furthermore, physically active rats had similar or decreased Mn 2+ uptake after versus before wheel running (6.8 vs 11.0% change), while sedentary rats appeared to have enhanced Mn 2+ uptake after versus before five weeks of sedentary conditions (16.3 vs 7.4% change). These initial findings support our hypothesis that sedentary conditions promote exaggerated neuronal activity in the RVLM, as indicated by greater Mn 2+ accumulation in sedentary versus physically active rats. Enhanced RVLM activity due to sedentary conditions may contribute to greater SNA and contribute to the mechanisms by which a sedentary lifestyle increases the risk of developing CVD in humans. Support or Funding Information DJH AHA 15PRE25700308; PJM NIH HL096787‐05A1, AHA 25810010; AGH USDVA 1I01RX001095‐011Rx; BAB NEI EY021619