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Knockdown of tyrosine hydroxylase in the nucleus of the solitary tract prevents attenuated body weight gain and blunts neuronal activation in the hypothalamus following chronic intermittent hypoxia (1126.4)
Author(s) -
Nedungadi T. Prashant,
Bathina Chandra,
Mifflin Steve
Publication year - 2014
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.28.1_supplement.1126.4
Subject(s) - medicine , endocrinology , hypothalamus , tyrosine hydroxylase , gene knockdown , intermittent hypoxia , lateral parabrachial nucleus , biology , immunohistochemistry , obstructive sleep apnea , parabrachial nucleus , apoptosis , biochemistry
Patients with sleep apnea (SA) are at a risk of developing metabolic syndrome. In the rat, 7 days of Chronic Intermittent hypoxia (CIH), a model of the arterial hypoxemia seen in SA patients, is associated with reduced body weight gain (p<0.005, n= 18), food intake (p<0.05, n=11), hyperinsulinemia (p<0.05, n=7), glucose intolerance and elevated fasting blood glucose levels (p<0.05, n=8). Brainstem melanocortins and other peptides has been well documented to be involved in metabolic homeostasis while tyrosine hydroxylase (TH) is known to be responsive to hypoxic stress; however the involvement of NTS TH neurons in regulating energy homeostasis following CIH has not yet been investigated. AAV‐TH shRNA virus was used to knockdown TH in the NTS of male rats, while virus with scrambled RNA was used as a control. Knockdown of TH in the NTS prevented the reduction in body weight following CIH (n=7) compared to scrambled virus injected rats and naïve rats subjected to CIH. Immunohistochemical staining for the neuronal activational marker FosB revealed elevated immunoreactivity following CIH (p<0.05, n=6) in the hypothalamic arcuate nucleus (ARH). Knockdown of TH resulted in reduced FosB staining in the ARH and dorsomedial hypothalamus while no change was observed in the lateral hypothalamic area. However, in the ventromedial hypothalamus, increased FosB staining was observed (p<0.05, n= 8). Our findings suggest that NTS TH neurons play an important role in regulating metabolic status during exposure to CIH and alter the neuronal activity in hypothalamic feeding centers, possibly via regulation of an anorexigenic signaling pathway. Grant Funding Source : P01 HL88052