Faculty Collaboration Database

Mortality and ventilatory effects of central serotonin deficiency during postnatal development depend on age but not sex. Physiol Rep 2021 Jul;9(13):e14946

Date

07/07/2021

Pubmed ID

34228894

Pubmed Central ID

PMC8259800

DOI

10.14814/phy2.14946

Scopus ID

2-s2.0-85109859087 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Serotonin (5-HT) influences brain development and has predominantly excitatory neuromodulatory effects on the neural respiratory control circuitry. Infants that succumb to sudden infant death syndrome (SIDS) have reduced brainstem 5-HT levels and Tryptophan hydroxylase 2 (Tph2). Furthermore, there are age- and sex-dependent risk factors associated with SIDS. Here we utilized our established Dark Agouti transgenic rat lacking central serotonin KO to test the hypotheses that CNS 5-HT deficiency leads to: (1) high mortality in a sex-independent manner, (2) age-dependent alterations in other CNS aminergic systems, and (3) age-dependent impairment of chemoreflexes during post-natal development. KO rat pups showed high neonatal mortality but not in a sex-dependent manner and did not show altered hypoxic or hypercapnic ventilatory chemoreflexes. However, KO rat pups had increased apnea-related metrics during a specific developmental age (P12-16), which were preceded by transient increases in dopaminergic system activity (P7-8). These results support and extend the concept that 5-HT per se is a critical factor in supporting respiratory control during post-natal development.

Author List

Mouradian GC Jr, Kilby M, Alvarez S, Kaplan K, Hodges MR

Authors

Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin
Gary C. Mouradian PhD Assistant Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Animals
Animals, Newborn
Body Temperature
Brain Stem
Female
Gene Knockdown Techniques
Hypercapnia
Hypoxia
Male
Mortality
Rats
Rats, Transgenic
Respiratory Physiological Phenomena
Serotonin
Sex Factors