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Age‐ and Inactivity‐Dependent Differences in Glutamate (GluN1) and GABA (GABA Aα1 ) Receptor Subunits in Subregions of the Rat Rostral Ventrolateral Medulla
Author(s) -
FykKolodziej Bozena,
Mueller Patrick
Publication year - 2021
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.2021.35.s1.03555
Subject(s) - rostral ventrolateral medulla , gabaergic , glutamatergic , medicine , endocrinology , glutamate receptor , gabaa receptor , brainstem , neuroplasticity , medulla oblongata , receptor , medulla , central nervous system , neuroscience , biology
The rostral ventrolateral medulla (RVLM) is an important brain region that regulates sympathetic vasoconstriction and cardiac function under normal conditions and in cardiovascular disease (CVD) states. Among the common, modifiable risk factors for CVD, a sedentary lifestyle is considered the number one cause of preventable death. Sedentary animals have greater blood pressure, and both greater sympathoexcitatory and sympathoinhibitory responses to in vivo activation and inhibition of the RVLM, respectively. Our recent studies also provide evidence of (in)activity‐related neuroplasticity in GABAergic and glutamatergic receptor systems in the RVLM and its rostral extension (RVLM RE ) (Mueller et al., 2020; Fyk‐Kolodziej et al., 2020). However, to our knowledge, no studies have tested the time course and mechanisms of (in)activity‐related neuroplasticity in RVLM subregions. The purpose of this study was to determine expression levels of GABA Aα1 and GluN1 receptor subunits in the RVLM and RVLM RE of four week‐old rats and following 4 or 12 weeks of sedentary or physically active conditions. We hypothesized that sedentary rats would exhibit subregionally‐specific increases in GABA Aα1 and GluN1 receptor subunits compared to four week‐old rats, and to 8 and 16 week‐old active rats. To this end, four week‐old, male Sprague‐Dawley rats were either sacrificed or provided running wheels (active) or normal caging (sedentary) for 4 (n=3 ea) or 12 weeks (GluN1, n=6 ea; GABA Aα1 , n=12 ea). Bilateral micropunches from 80 μm brainstem cryosections were obtained from all animals and pooled individually into RVLM and RVLM RE subregions relative to the caudal pole of the facial nucleus (FN0). The RVLM included tissue 480 µms caudal to FN0; whereas, the RVLM RE consisted of tissue 480µms rostral to FN0. Western blotting in 4 week‐old animals revealed possibly higher GABA Aα1 expression in the RVLM RE vs. RVLM region (1.15±0.01 vs. 0.93±0.04, p =.07, n=3), with the same pattern of higher GABA Aα1 expression in the RVLM RE vs. RVLM in rats after 4 or 12 weeks of sedentary ( p <.001 both time points) or active conditions ( p =.025 and p =.011, respectively). In sixteen week‐old sedentary rats had lower expression of GABA Aα1 within the RVLM region only ( p =.004; RVLM RE p =.64) vs. active rats. Similar to GABA Aα1 , GluN1 expression was higher in the RVLM RE vs. RVLM of 4 week‐old rats, (1.18±0.06 vs. 0.81±0.06, p =.003; n=3). In contrast, after 4 weeks of sedentary or physically active conditions, the RVLM and RVLM RE showed similar GluN1 expression levels ( p =.23 both groups). Sixteen week‐old sedentary rats showed higher GluN1 expression in RVLM compared with 4 week‐old animals (1.25±0.07 vs. 0.81±0.06, p <.001) and compared to sixteen week‐old, active rats (0.93±0.06, p =.001). These results suggest that sedentary conditions produce considerable neuroplasticity in GABAergic and glutamatergic systems in subregions of the RVLM via changes in receptor expression. Our findings are consistent with previous data demonstrating enhanced sympathoinhibitory and sympathoexcitatory responses observed in sedentary rats in vivo and are likely related to the increased incidence of CVD associated with a sedentary lifestyle.