Butyrylcholinesterase Is Not Required for the Neonatal Autoresuscitation Reflex

Abstract

Sudden Infant Death Syndrome (SIDS) is the leading cause of infant death under the age of one year of age, taking the lives of more than 1,400 infants annually, and comprising approximately 41% of all Sudden Unexpected Infant Death (SUID) cases. SIDS etiology remains vastly unknown but is best explained via a triple risk model that proposes SIDS occurs in a vulnerable infant during a critical developmental period when triggered by an external stressor. In SIDS it is hypothesized that there is first a failure in arousal followed by failure in the protective autoresuscitation reflex; a defense mechanism for an infant that is in a hypoxic coma, that promotes deep gasping to attempt to restart cardiovascular function. Many SIDS case studies reveal associations with genetic variants and abnormal biomarkers; however, it is unclear whether these variants are causal. Recently a case study identified a broad association between reduced blood BChE activity and SIDS cases, yet the functional relationship between BChE and respiratory regulation remains to be investigated. We aimed to functionally test the relationship between BChE and the neonatal autoresuscitation reflex utilizing a rapid pipeline for precision genetic modeling and high-throughput functional testing developed by the Ray Lab. BChE loss of function mice, generated through targeted genetic editing, were tested for neonatal autoresuscitation on our automated closed loop phenotyping platform, Looper. Postnatal day 7-8 mice were exposed to 3% CO2 and 97% N2 stimuli to induce a state of hypoxia resulting in detection of bradycardia, initial hyperventilation, hypoventilation, and apnea followed by restoration of room air conditions to facilitate the autoresuscitation reflex and cardio-respiratory recovery. Male and female mice were exposed to repeated anoxic gas challenges and allowed to autoresuscitate until death occurred. Data suggest that loss of BChE function does not affect neonatal autoresuscitation. BChE knockout mice and heterozygous mice survived similar amounts of anoxic challenges as wild type controls. No sex differences were observed between the number of anoxic challenges survived in males and females for all genotypes. Our data demonstrate the first functional assessment of BChE in neonatal cardio-respiratory regulation and the autoresuscitation response and highlight that BChE is not required for successful neonatal autoresuscitation. Additional analyses of respiratory parameters from respiratory trace data for BChE loss of function mice will aid in a further understanding if BChE loss of function is implicated in other aspects respiratory regulation. Funding: Precision Core funding U54 OD030165. NIH/NHLBI R01HLN161142-01 and R01HL130249-07. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.