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Effects of leptin in the retrotrapezoid nucleus (RTN) on CO2‐sensitivity and respiration.
Author(s) -
Bassi Mirian,
Furuya Werner Issao,
Menani José Vanderlei,
Almeida Colombari Débora Simões,
Carmo Jussara Márcia,
Silva Alexandre,
Hall John Edward,
Wenker Ian C,
Mulkey Daniel,
Colombari Eduardo
Publication year - 2013
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.27.1_supplement.1137.12
Subject(s) - leptin , medicine , leptin receptor , endocrinology , chemoreceptor , chemistry , patch clamp , receptor , energy homeostasis , biology , obesity
Evidence suggests that, in addition to regulate energy homeostasis, leptin also contributes to the CNS control of breathing in response to changes in CO 2 /H + (i.e., central chemoreception). However, cellular targets of leptin‐dependent drive to breathe have not been elucidated. Here, we tested the effects of leptin on hypercapnic ventilatory response in leptin deficient mice (ob/ob: 42±2 g) in vivo , and on CO 2 ‐responsiveness of RTN neurons and astrocytes in brain slices isolated from rat pups (P7–12). We found that 3‐ day unilateral RTN injections of leptin (1 μg/100 nl, n=7/group) increased ventilatory responsiveness to 7% CO 2 in ob/ob mice (4378±294 μl.min −1 .g −1 , vs. 2849±319 μl.min −1 .g −1 in vehicle group). Immunohistochemical analysis using antibodies for leptin receptors, astrocytes (aldehyde dehydrogenase 1L1) and neurons (biocytin) suggest that leptin receptors are expressed by RTN astrocytes but not neurons in ob/ob mice. We also found that acute in vitro exposure to leptin in RTN slices (10 min, 50 nM) elicited no effect on excitability of chemosensitive neurons (cell‐attached current clamp) or conductance of CO 2 ‐sensitive astrocytes (whole‐cell voltage clamp; Ihold −80 mV). These results suggest that although long‐term application of leptin into the RTN increased respiratory drive in ob/ob mice, the cellular and molecular mechanisms remain unclear.