Brain-derived neurotrophic factor mRNA and protein in the piglet brainstem and effects of Intermittent Hypercapnic Hypoxia

Abstract

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for the development of normal respiratory rhythm and ventilatory control. Chronic exposure to Intermittent Hypercapnic Hypoxia (IHH) has been shown to alter ventilatory responses of piglets. This study investigated changes in BDNF distribution and expression in seven nuclei of the caudal medulla, from piglets exposed to IHH for 1, 2, 3, or 4 days before death, using non-radioactive in situ hybridisation (for mRNA) and immunohistochemistry (for protein). Compared to controls, BDNF mRNA was markedly increased across the entire medulla of the brainstem, after all durations of IHH (1–4 days). In contrast, BDNF protein expression increased after 1 day of exposure to IHH ( p=0.003), but, thereafter, was not different to controls. Amongst individual nuclei, neurons of the dorsal motor nucleus of the vagus (DMNV) showed increased BDNF mRNA ( p<0.01), but decreased protein expression ( p=0.05) after all durations of IHH. In the ION, both mRNA and protein for BDNF were significantly increased after 1 day IHH ( p<0.01 and p=0.001, respectively), but these increases were not sustained. This study is the first to investigate changes in BDNF expression in response to environmental challenges during postnatal development in the brainstem. Implications of the wide distribution of BDNF in the piglet caudal medulla and increased expression after IHH exposure are discussed, with particular reference to roles for BDNF-dependant neurons at this stage of development.