Neonatal caffeine treatment does not induce long-term consequences on TrkB receptors or BDNF expression in chemosensory organs of adult rats

Abstract

Chronic treatment with caffeine during the neonatal period (neonatal caffeine treatment, NCT, 15 mg/kg/day from P3 to P12, oral gavage) has long-lasting consequences on respiratory control development. In adult male (but not female) rats, prior exposure to NCT results in a greater respiratory frequency response to hypoxia. This sex-specific effect of NCT was accompanied by an augmented expression of adenosine A 2A receptors (A 2AR) in the carotid body (CB) but not in the nucleus tractus solitarius (NTS). Since activation of adenosine A 2AR can directly stimulate synthesis of tyrosine kinase B receptor (TrkBR) and brain-derived neurotrophic factor (BDNF), we determined whether NCT increases TrkBR and BDNF expression levels in the CB and NTS using both RT-PCR and western blot analyses. CB, NTS, and superior cervical ganglion were collected from adult male and female rats (10–12 weeks old) previously subjected to NCT or to control (neonatal water treatment, NWT). In male rats, when NCT tended to decrease TrkBR mRNA transcript levels by about 32% in the CB and to reduce BDNF transcripts in the NTS by 22%, western blot analyses showed no parallel changes in final protein expression. NCT had no effects on TrkBR or BDNF mRNA and protein levels in the CB and NTS of female rats. Neither gene was altered by NCT in the superior cervical ganglion of male and female rats. These data suggest that NCT has no long-term effects on trophic factor BDNF and TrkBR expression at peripheral and central level of chemosensory organs involved in respiratory control.