Perinatal hyperoxia alters the expression of neurotrophic factors and their receptors in the rat carotid body

Abstract

Perinatal hyperoxia attenuates the hypoxic ventilatory response in rats by altering development of the carotid body and its afferent neurons. We hypothesized that these changes in carotid body growth and innervation involve changes in the expression of neurotrophic factors or their receptors. Rats were born and raised in hyperoxia (60% O2) or normoxia (21% O2) until studied at 1–14 days of age (i.e., P1–P14). Carotid body volume was 30% smaller in hyperoxia‐reared rats than their normoxia‐reared counterparts by P4 (P=0.02) and showed little growth thereafter. In contrast, carotid bodies of normoxia‐reared rats more than doubled in size between P4 and P14. We measured mRNA expression for brain‐derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (Trk B), and glial cell line‐derived neurotrophic factor (GDNF) and its receptor Ret in carotid bodies at P3 via quantitative RT‐PCR. Ret expression was reduced ~30% in hyperoxia‐treated rats (P<0.01), but no differences were detected for BDNF, TrkB, or GDNF. In addition, BDNF and GDNF protein expression levels were measured at P3 via ELISA. BDNF was reduced by ~70% in the carotid bodies of hyperoxia‐treated rats (P=0.02). GDNF appeared to decrease, depending on normalization methods. These data suggest a role for neurotrophic factors in hyperoxia‐induced respiratory plasticity. Supported by NIH grant P20 RR‐016463 (Maine INBRE).