Increasing brain serotonin corrects CO2 chemosensitivity in methyl‐CpG‐binding protein 2 (Mecp2)‐deficient mice

New Findings • What is the central question of this study?Mice deficient in methyl‐CpG‐binding protein 2 (Mecp2; a model of Rett syndrome) display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. Patients and mice show reduced levels of brain 5‐HT, which is important in central chemosensitivity. It is not known whether increasing 5‐HT in this mouse model would improve their respiratory response to CO2. • What is the main finding and its importance?We show, for the first time, that females heterozygous for the Mecp2 mutation have a higher hypocapnic threshold for apnoeas versus wild‐type mice and that increasing 5‐HT in Mecp2‐null males, with citalopram, can correct CO2 chemosensitivity, a finding that may be important clinically. Mice deficient in the transcription factor methyl‐CpG‐binding protein 2 (Mecp2), a mouse model of Rett syndrome, display reduced CO2 chemosensitivity, which may contribute to their breathing abnormalities. In addition, patients with Rett syndrome and male mice that are null for Mecp2 show reduced levels of brain serotonin (5‐HT). Serotonin is known to play a role in central chemosensitivity, and we hypothesized that increasing the availability of 5‐HT in this mouse model would improve their respiratory response to CO2. Here we determined the apnoeic threshold in heterozygous Mecp2‐deficient female mice and examined the effects of blocking 5‐HT reuptake on the CO2 response in Mec...
Source: Experimental Physiology - Category: Physiology Authors: Source Type: research