Toluene Alters p75NTR Expression in the Rat Brainstem

Toluene is a neurotoxic organic solvent widely used in industry. Acute toluene administration in rats induced a significant increase in the numbers of neural cells immunostained for p75 NTR in several brainstem regions, such as the raphe magnus and the nucleus of the solitary tract, as well as in the lateral reticular, gigantocellular, vestibular and ventral cochlear nuclei, without any in the facial and spinal trigeminal nuclei and the dorsal horn of the spinal cord. These data suggest that p75 NTR could be involved in toluene-induced neurotoxic efffects in the rat brainstem. The experimental animals, male Sprague-Dawley rats (3 months old), were carefully handled and all experiments were carried out in accordance with the law, avoiding animal suffering. Toluene with purity of 99% (Analytical reagent grade, Quimon Chem. Co., Spain) was used. Toluene was diluted with olive oil at a concentration of 1 ml/ml and administered intraperitoneally to the experimental group (n=6) at a dose of 1.3 ml/kg/day for 5 consecutive days. The selected dose was 1/2 of the LD 50 per day. The LD50 in rats has been found in our laboratory to be 2.61 ± 0.41 ml/ kg/day, calculated by the Bliss method. The control group (n=6) was given 0.9% NaCl solution in the same volume and duration as the experimental group. Two hours after the last treatment, the animals were anaesthetized with Equithensin (2 ml/kg), an alcoholic solution of nembutal and chloral hydrate (Sigma-Aldrich Quimica S. A.), intraperitoneally and perfused transcardially under deep anaesthesia with saline plus 50 mM phosphate buffer, pH 7.4, followed by 4% paraformaldehyde (Sigma-Aldrich Quimica S. A.). The brainstems were removed, cut in two pieces and then immersed in the same fixative medium overnight.