title: Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats.
abstract: Hypertension leads to structural and functional changes at baroreceptor synapses in the medial nucleus tractus solitarius (NTS), but the underlying molecular mechanisms remain unknown. Our previous studies show that brain-derived neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG) neurons, including baroreceptor afferents and their central terminals in the medial NTS. We hypothesized that hypertension leads to upregulation of BDNF expression in NG neurons. To test this hypothesis, we used two mechanistically distinct models of hypertension, the spontaneously hypertensive rat (SHR) and the deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood pressure was significantly elevated compared with age-matched Wistar-Kyoto (WKY) control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG. BDNF transcripts from exon 4, known to be regulated by activity, and exon 9 (protein-coding region) showed the largest increases. Electrical stimulation of dispersed NG neurons with patterns that mimic baroreceptor activity during blood pressure elevations led to increases in BDNF mRNA that were also mediated through promoter 4. The increase in BDNF content of the NG in vivo was associated with a significant increase in the percentage of BDNF-immunoreactive NG neurons. Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a significant increase in BDNF in the NTS region, the primary central target of NG afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension.
authors.affiliation: Department of Integrative Biosciences, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Anke
authors.initials: A
authors.lastname: Vermehren-Schmaedick
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Jenkins
authors.forename: Hui-ya
authors.initials: HY
authors.lastname: Hsieh
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Brown
authors.forename: Mollie P
authors.initials: MP
authors.lastname: Page
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Brooks
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Balkowiec
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003900:Desoxycorticosterone / Q000633:toxicity; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008901:Mineralocorticoids / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009620:Nodose Ganglion / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008901:Mineralocorticoids; D012333:RNA, Messenger; C571820:brain-derived integrating factor-1, rat; D003900:Desoxycorticosterone