Altered ventilatory and thermoregulatory control in male and female adult Pet-1 null mice

详细信息    查看全文

• 作者：Matthew R. Hodges^a ; ^b ; ^{mhodges@mcw.edu"" rel=""nofollow} ; Simon Best^a ; George B. Richerson^a ; ^c ; ^d
• 关键词：Ventilation ; Thermoregulation ; Pet-1 ; Serotonin (5-HT)
• 刊名：Respiratory Physiology & Neurobiology
• 出版年：2011
• 出版时间：31 July 2011
• 年：2011
• 卷：177
• 期：2
• 页码：133-140
• 全文大小：574 K

文摘

The integrity of the serotonin (5-HT) system is essential to normal respiratory and thermoregulatory control. Male and female transgenic mice lacking central 5-HT neurons (Lmx1b^f/f/p mice) show a 50 % reduction in the hypercapnic ventilatory response and insufficient heat generation when cooled ([Hodges and Richerson, 2008a] and [Hodges et al., 2008b]). Lmx1b^f/f/p mice also show reduced body temperatures (T_body) and O₂ consumption , and breathe less at rest and during hypoxia and hypercapnia when measured below thermoneutrality (24 °C), suggesting a role for 5-HT neurons in integrating ventilatory, thermal and metabolic control. Here, the hypothesis that Pet-1 null mice, which retain 30 % of central 5-HT neurons, will demonstrate similar deficits in temperature and ventilatory control was tested. Pet-1 null mice had fewer medullary tryptophan hydroxylase-immunoreactive (TPH⁺) neurons compared to wild type (WT) mice, particularly in the midline raphé. Female (but not male) Pet-1 null mice had lower baseline ventilation , breathing frequency (f), and T_body relative to female WT mice (P < 0.05). In addition, and were decreased in male and female Pet-1 null mice during hypoxia and hypercapnia (P < 0.05), but only male Pet-1 null mice showed a significant deficit in the hypercapnic ventilatory response when expressed as % of control (P < 0.05). Finally, male and female Pet-1 null mice showed significant decreases in T_body when externally cooled to 4 °C. These data demonstrate that a moderate loss of 5-HT neurons leads to a modest attenuation of mechanisms defending body temperature, and that there are gender differences in the contributions of 5-HT neurons to ventilatory and thermoregulatory control.