SERT knock‐out mice have altered control of breathing and thermoregulation

Abstract

Serotonin (5HT) transport protein (SERT) knock-out (KO) mice have increased anxiety-like behaviors and decreased aggression associated with absent brainstem SERT, increased 5HT synthesis and extracellular levels, decreased 5HT1A receptors and decreased 5HT neuron firing rates (Kim et al., Neuropharm 2005). This pattern of neurochemical abnormalities is similar to that recently described in the brainstem of Sudden Infant Death Syndrome (SIDS) cases, namely, increased numbers of 5HT neurons, decreased 5HT1A binding and decreased SERT per 5HT neuron (Paterson et al., JAMA 2006). Here we evaluate ventilatory and thermoregulatory physiology in adult SERT KO mice of both genders during wakefulness. Ventilation was measured in un-instrumented control and SERT-KO mice using whole body plethysmography. While breathing air, male KO mice breathed faster and tended to hypoventilate while female KO mice breathed like controls. With 5% CO2 stimulation, male KO mice had a 39–46% decrease in their response compared to control males or KO females. With 10% O2 stimulation, the VE/VO2 responses of KO mice of both genders were decreased compared to controls. To test thermoregulation we placed individually housed mice into a cold room (4°C) for 120 min. Females had a ~3.0°C drop in body temperature while males and controls had a 0.9 and 1.4°C drop, respectively. Awake, adult SERT-KO mice have gender specific abnormalities in the control of breathing (males) and in the regulation of body temperature in the cold (females) and both genders have altered responses to hypoxia. Such abnormalities could contribute to a lessening of physiological regulatory system function and provide possible insight into mechanisms involved in SIDS as many SIDS cases exhibit anatomical abnormalities in the brainstem 5HT system as well as a genetic association with SERT allele distribution. (Support By: NIH HL 28066, NICHD 36379).