Cobalamin deficiency-induced down-regulation of p75-immunoreactive cell levels in rat central nervous system.

We investigated immunoreactivity for p75 neurotrophin receptor (NTR) in the spinal cord white matter and septum of rats made cobalamin-deficient (Cbl-D) by means of total gastrectomy or a Cbl-D diet. Cbl deficiency down-regulates p75NTR-immunoreactive cell levels in spinal cord white matter and septum with different time courses. On the whole, the spinal cord white matter seems to be more affected in terms of p75NTR-immunoreactive cells, most of which are astrocytes. The p75NTR-immunoreactive cell levels in the spinal cord white matter and septum normalized in rats treated with Cbl (scheme b) and killed 4 months after total gastrectomy. However, Western blot analysis of p75NTR in the spinal cords of Cbl-D rats shows increased p75NTR protein levels, which are resistant to Cbl replacement. These findings demonstrate that a neurotrophic vitamin (Cbl) positively regulates the levels of a neurotrophic receptor (p75NTR) (at least in terms of immunohistochemistry) in rat central nervous system, although the underlying mechanism(s) are still unknown.

Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection.

RATIONALE: Nerve growth factor and its receptors are upregulated in the lungs of weanling rats with lower respiratory tract infection caused by the respiratory syncytial virus (RSV), and this is a major mechanism of the inflammatory response against the virus. However, no information is available in humans. OBJECTIVES: We sought to determine whether the expression of neurotrophic factors and receptors is increased in human infants infected with RSV. METHODS: We used a highly sensitive immunoassay to measure the concentrations of nerve growth factor and brain-derived neurotrophic factor proteins in serum samples and in the supernatants and cell fractions of nonbronchoscopic bronchoalveolar lavage fluid. We also used immunofluorescence to detect expression in airway cells of the tyrosine kinase receptor TrkA, which binds nerve growth factor with high affinity. Samples were obtained at 24 and 48 hours postintubation from 31 mechanically ventilated infants: 15 patients with RSV infection, 5 patients with respiratory infection negative for RSV, and 11 postsurgical patients without respiratory infection. MAIN RESULTS: Data show significantly higher concentrations of both neurotrophins in the cell fractions of bronchoalveolar lavage samples obtained from infants with RSV infection compared with control infants, whereas no significant difference was found in supernatants or serum samples. We also detected tyrosine kinase receptor immunoreactivity only in cells from airways infected with RSV. CONCLUSIONS: We conclude that neurotrophic factors and receptors are overexpressed in human airways infected by RSV, and may contribute to airway inflammation and hyperreactivity.